a review of conflict of interest, competing interest, and bias for toxicologists
TRANSCRIPT
http://tih.sagepub.com
Toxicology and Industrial Health
DOI: 10.1177/0748233708089046 2007; 23; 557 Toxicol Ind Health
LD Claxton A review of conflict of interest, competing interest, and bias for toxicologists
http://tih.sagepub.com/cgi/content/abstract/23/10/557 The online version of this article can be found at:
Published by:
http://www.sagepublications.com
can be found at:Toxicology and Industrial Health Additional services and information for
http://tih.sagepub.com/cgi/alerts Email Alerts:
http://tih.sagepub.com/subscriptions Subscriptions:
http://www.sagepub.com/journalsReprints.navReprints:
http://www.sagepub.com/journalsPermissions.navPermissions:
http://tih.sagepub.com/cgi/content/refs/23/10/557SAGE Journals Online and HighWire Press platforms):
(this article cites 82 articles hosted on the Citations
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
A review of conflict of interest, competing interest,and bias for toxicologists
LD Claxton
Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory,U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA
One of the issues often associated with scientific misconduct is conflict of interest. Although there isa lack of uniformity in the definition of conflict of interest, many express concerns that competinginterests may bias research methods and the interpretation of data and conclusions. In extremecases, conflict of interest activity could contribute to scientific misconduct, hinder the training ofscientists, delay the dissemination of research results, lead to the harming of human health and theenvironment, and misdirect society’s decisions that rely on science. This article is not a commentaryor editorial but an attempt to supply an overview of what has been said, researched, and accom-plished in the area of conflict of interest for toxicologists. Discussion of the financial, professional,and philosophical concerns associated with conflict of interest will be followed by brief discussion ofgeneral management approaches and the roles of scientists and organizations from all sectors (i.e.,academia, industry, non-profit organizations, and government). Toxicology and Industrial Health2007; 23: 557–571.
Key words: academia; bias; competing interest; conflict of interest; editors; ethics; government;industry; journals; law; non-profit organizations; scientific societies; toxicology
Introduction
General background
Conflict of interest (CoI) has been the subject oflively discussions in universities (Behrens andGray, 2001; Bozeman and Gaughan, 2007; Evansand Packham, 2003; George, et al., 2002; Gluck,et al., 1987; Hasselmo, 2002; Kenney, 1987; Kod-ish, et al., 1996; Sugarman, 2005), government(Brodsky, 2007; Gold, 2006; Kondro, 2006; Stark,2006; Steinbrook, 2004), scientific journals (Annals
of Internal Medicine Editors, 2004; Barnes andBero, 1998; Fugh-Berman, 2005; Goozner, 2004;Rumsey, 1999; Van McCrary, et al., 2000), andthe popular press (Labaton, 2007; Markowitz andRosner, 2002; Newman, 2007). Within the scientificcommunity, there appears to be much disagreementand misunderstanding about the phrase ‘conflict ofinterest’ (Boyd and Bero, 2006; Friedman, 1992).‘Beauty is in the eye of the beholder’ (a third-century BC Greek saying later used in the novelMolly Bawn by Margaret Wolfe Hungerford)could be paraphrased by some to say ‘conflict ofinterest is in the eye of the beholder’ (Friedman,1992). Some understand any CoI to always beimproper, whereas others understand CoI as onlyprimary and secondary interests that conflict and
Toxicology and Industrial Health 2007; 23: 557–571
http://tih.sagepub.com
© 2007 SAGE Publications 10.1177/0748233708089046Los Angeles, London, New Delhi, Singapore
Correspondence to: Environmental Carcinogenesis Division, NationalHealth and Environmental Effects Research Laboratory, U.S. Envi-ronmental Protection Agency, Research Triangle Park, North Caro-lina 27711, USA. Email: [email protected]
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
that may or may not lead to inappropriate actions.Pronin, et al. (2004) say that the “lack of balancebetween self-perception and social perception arisesfrom the simple fact that other people’s actions,judgments, and priorities sometimes differ fromone’s own.” In other words, individuals are morelikely to recognize poor judgment and actions inothers than seeing the same in themselves. Theenvironmental activist may see academic researchsponsored by industry as improper CoI, whereasindustry’s management says that sponsoring inde-pendent research at a university creates more cred-ibility than can be achieved by its own scientists.The industrial representative may see evidence ofimproper CoI when a health foundation funds con-tract research that is likely to serve the foundation’sinterests; however, a foundation may find this themost cost effective way to create the informationneeded to serve the public. Does a governmentresearcher who is a member of a radical environ-mental group (or on the other hand, in collabora-tion with industrial scientists) have an improperCoI? For a toxicologist, when must he/she revealhis CoI or competing interest, and when do his/her opinions merely constitute a bias that doesnot require revelation?
There are many types of CoI; therefore, debatesover CoI include concerns that there are manyinfluences that bias the conducting and interpretingof research, contribute to scientific misconduct,hinder the training of scientists, delay the dissemi-nation of research results, harm human health andthe environment, and misdirect society’s decisionsthat rely on science (Barrow and Conrad, 2006a;Behrens and Gray, 2001; Bekelman, et al., 2003;Bozeman and Gaughan, 2007; Campbell, et al.,1998; Friedman and Richter, 2005; Hutton andMassey, 2006). Evidence demonstrates that thereis a correlation between breakdowns in researchintegrity and specific financial ties (Boyd andBero, 2006). CoI has been documented in all sec-tors of society (Arenson, 2007; Labaton, 2007;Newman, 2007; Sengupta, 2007). Within the lifesciences, CoI has been most evident (although notnecessarily most frequent) in the medical commu-nity (Barnes and Bero, 1997; Bekelman, et al.,2003; Chisolm, 2007; Cho and Bero, 1996; Lexchin,et al., 2003).Misconduct involving the toxicologicalsciences and CoI have been recognized (Markowitz
and Rosner, 2002; Stark, 2000). However, CoIissues in the toxicological sciences have been thor-oughly reviewed only in the case of tobacco smoke(Barnes and Bero, 1998; Behrens and Gray, 2001;Fields and Chapman, 2003; Ong and Glantz, 2001;Samet and Burke, 2001; Yach and Bialous, 2001);therefore, a review of CoI issues for toxicologists isneeded.
Friedman (1992) contends that the understand-ing of CoI is damaged by semantics. He contendsthat when an individual or organization has two ormore competing interests, a conflict must exist. Asa part of his argument, this conflict only becomes aproblem when it creates a bias that leads to errone-ous results or incorrect advice. In other words, it isnot the conflict that is in the wrong, but the result-ing biased judgment and/or misconduct. In con-trast, in the 2005 Society of Toxicology (SOT)workshop on CoI, bias was spoken of as a tendencythat any scientist would have from his/her training,research, and experiences, and as such, bias is ‘vir-tually inherent’ in science (Maurissen, et al., 2005).Such divergent discussions illustrate that semanticspresent a barrier to resolving the issues. In anattempt to have a ‘working definitions’ for this arti-cle, publications from a number of authoritativebodies were examined (Boyd and Bero, 2006;Brockway and Furcht, 2006; Callaham, 2003;Committee on Publication Ethics (COPE), 2003,2007; Food and Drug Administration, 2007;ICMJE, 2006; Lehman-McKeeman and Peterson,2003; Maurissen, et al., 2005; National Institutefor Health and Clinical Excellence, 2007; Stark,2000; U.S. Congress, 1972). For example, theWorld Health Organization (WHO) defines CoI(Boyd and Bero, 2006) as “A conflict of interestexists when an individual’s secondary interests(e.g. personal, financial) interfere with or influencejudgments regarding the individual’s primary inter-ests (e.g. patient welfare, education, researchintegrity).” By examining such definitions, onesees that common definitions are starting to emergefrom the literature. In summary these definitionsare the following:
� A CoI is a situation in which an individual ororganization has competing primary and sec-ondary interests. A CoI may strongly predisposean individual or organization to exploit a pro-fessional or an official capacity in some way for
A review of conflict of interestLD Claxton
558
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
personal or organizational benefit. An improperCoI occurs when an individual’s or organiza-tion’s interests unduly influence judgments con-cerning professional responsibility (Bekelman,et al., 2003; Boyd and Bero, 2006; Stark, 2000;Thompson, 1993).
� Competing interests is a term synonymous withCoI but may not carry the negative implicationsof the term CoI.
� A bias refers to a preference or an inclination(that may occur from a CoI) that tends to inhibitimpartial judgment. A bias may generate theprejudice that leads to unfair actions or policies.
An illustration of CoI debates and disagreements
As CoI issues have become more prominent, a vari-ety of debates have been conducted in high-profilejournals through commentaries, letters, news arti-cles, and editorials. The following illustrates howCoI debates are interconnected and are influencedby the participants’ perspectives (biases). Examina-tion of opposing positions leads to a better under-standing of the overall CoI debate.
Devine (2001) asserted that industry dominatesthe creation, analysis, and review of toxicologicaldata related to new chemicals; thus, the ultimatecharacterization of the health effects of a chemicalcan be skewed by a single viewpoint. In support ofthis viewpoint, Devine criticized the role that indus-try played in the development of cancer guidelines(available at http://www.epa.gov/ord/researchac-complishments/cancer.html) and the health assess-ments for arsenic, vinyl chloride (VC), butadiene,and dioxin (available at http://cfpub.epa.gov/ncea/iris/index.cfm). On December 9, 2004, the Centerfor Science in the Public Interest (CSPI) called ona federal agency to remove two industrial scientistsfrom a list of potential candidates for an advisorycommittee that would evaluate the health riskposed by an industrial chemical. The basis of theirobjection was that the two scientists either didresearch or worked for the companies that hadmanufactured the chemical. Their objection reliednot only on their interpretation of the CoI sectionof the Federal Advisory Committee Act (FACA)(available at http://www.gsa.gov/Portal/gsa/ep/con-tentView.do?contentType = GSA_DOCUMENT&contentId = 8890&noc = T) but also on the per-ception of CoI. Furthermore, CSPI stated thatthere were seven other scientists employed by or
related to the chemical industry to which they hadno objection. Sass, et al. (2005) maintained that thecancer risks and potency estimates for VC weredownplayed by industrial scientists and consul-tants. Also, Sass, et al. (2005) argued that the riskassessment for VC was unduly influenced by indus-try even before the issuing of a public notice invit-ing submission of technical information. The indus-trial position was dependent on a review publishedby a leading epidemiologist (Doll, 1988), in whichhe minimized the significance of the risk of cancerin all sites other than liver. However, Doll (1988)failed to acknowledge that his assessment wasfunded by a chemical industry organization,which was later revealed in a legal deposition in atoxic tort case.
In a commentary, Barrow and Conrad (2006a)criticized the above groups for challenging theplacement of industrial scientists on scientificreview panels. They defended industrial scientistsby saying that their efforts are highly regulated,meet high scientific standards, and do not suppressresults that are adverse to industry’s interest. Not-ing that no federal laws, rules, or policies presumethat the source of funding itself discredits any sci-entific work, they contended that industrial scien-tists (even who have vested interests) should not bedisqualified but included in advisory panels so thata balanced viewpoint can be obtained. This Barrowand Conrad debate was continued in responses alsopublished in the same issue of EnvironmentalHealth Perspectives. On behalf of CSPI, Goozner(2006) asserted that the CSPI objection to specificindustrial scientists was not because they were fromindustry but that they currently or previouslyworked for the manufacturer of the chemical.Thus, CSPI believed that this was not ordinarybias but a CoI that should disqualify the scientists.Goozner (2006) also pointed out that no objectionswere given by CSPI to other industrial scientistsbeing on the same review committee. In herresponse, Sass (2006) provided examples of wheregovernment’s checks and balances were not effec-tive for preventing biased or bad science. Sherecommended that agencies adopt the InternationalAgency for Research on Cancer (IARC) guidelineswhich allow financially conflicted experts to speakto IARC committees but bars them from anydecision-making roles. In their response, Barrow
A review of conflict of interestLD Claxton
559
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
and Conrad (2006b) pointed out that CoI disquali-fications under federal standards only apply to cur-rent employment or ownership. They counteredSass’s examples by suggesting that governmentfunded scientists may feel a need to publish adverseoutcomes, thus biasing their work against industrialchemicals.
The illustration above describes the type of issuesthat surround CoI. All sides contend that they areonly trying to promote high-quality science, servethe public good, and follow the legal and ethicalfoundations of their profession. Such debates arecertain to continue. Only by examining individualcases can we come to understand the different sidesof CoI issues. For example, Sass (2006) reports thatDearfield, et al. (1993) observed a selection bias infavor of industry’s results for the mutagenicity ofatrazine when tested by industry (which producedno evidence of mutagenicity) compared to the pub-lished literature in which mutagenic results wereobtained. Barrow and Conrad (2006a) argue thatpublished government-sponsored research alsocould be biased. On close examination of thepaper by Dearfield, et al. (1993), one can surmisethat the objectives of industry-submitted data anddata submitted by others to journals were different.Industry may have been trying to submit onlyrequired assays while minimizing cost, whereasindependent investigators may have taken a muchbroader view of what assays and assay modifica-tions were likely to show atrazine and related com-pounds mutagenic. In this case, employment did,therefore, shape a scientist’s viewpoints, objectives,and biases. For example, an industrial scientist maywork to meet regulatory needs on behalf of his/heremployer, and an academic scientist must demon-strate creative, state-of-the-art research for careeradvancement.
Therefore, a number of questions remain, for alltoxicologists:
� Does a scientist’s present or prior employmentsimply bias one’s viewpoint or unduly influenceone’s judgment?
� To what extent does professional pride in previ-ous research findings, publications, and presen-tations contribute to bias and CoI?
� Should government and government-fundedscientists or foundation-funded scientists be
scrutinized for CoI issues in the same way asindustrial or industry-funded scientists?
� Are industrial scientists who later go to work forgovernment or academia unduly influenced bytheir former relationships?
� Conversely, what effect does industrial employ-ment have on scientists formerly employed by agovernment agency or an academic institution?
Clearly, the tobacco industry used the expertiseof scientists in an inappropriate manner by deliber-ately withholding CoI information and scientificinformation from the public and other scientists(Fields and Chapman, 2003; Friedman, et al.,2005; Garne, et al., 2005; Ong and Glantz , 2001;Smith, 2007; Yach and Bialous , 2001). Tobaccoindustry efforts to develop their own version of‘good epidemiological practice’ and ‘soundscience’(Ong and Glantz , 2001) created mistrusts in bothindustrial- and government-sponsored research andrisk assessments. This mistrust is now causingothers to examine the influence of other industrialsectors on scientific CoI issues, especially undis-closed CoI (Check, 2007; Dalton, 1999, 2003,2007; Hardell, et al., 2007; Nature Editorial, 2007).
Purpose and approachThis publication is not a commentary or editorial;instead, it is an attempt to supply an overview ofwhat has been said, researched, and accomplishedin the area of CoI that can applied to the toxicolog-ical sciences. This is an attempt to facilitate the dis-cussions on CoI. Unless stated otherwise, CoI,competing interests, and bias will refer to the defi-nitions given in General Background.
Methods
A computerized search used the PubMed/Toxlinedatabase and Scopus for articles on CoI in thesciences. Based on their titles (and abstracts if avail-able), the articles were narrowed to those involvingthe toxicological sciences. For topical areas notadequately covered by these articles, a few over-view articles dealing with the life sciences and thelaws concerning CoI were used as the basis for dis-cussion. The book by Stark (2000) also provided anexcellent general reference on CoI. Additionalreferences were identified from the referencesections of the articles obtained, from the author’s
A review of conflict of interestLD Claxton
560
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
personal reference files (e.g., book chapters andgovernment reports), and from colleagues. Theresulting references contained many commentaries,letters, and editorials; therefore, many of thethoughts expressed were both repetitive and subjec-tive. Therefore, the results should not be consideredexhaustive. The author has attempted to referencecritical publications that present objective studiesand/or surveys.
Types and examples of CoIFinancialMost discussion about CoI revolves around finan-cial CoI because the public expresses a high anxietylevel about the influence of financial support on theresearch process (Bekelman, et al., 2003). Althoughreports that connect financial funding sources withthreats to scientific integrity are primarily associ-ated with the medical profession, especially clinicaltrials (Bekelman, et al., 2003), there is concern overfinancial CoI issues among toxicologists (Mauris-sen, et al., 2005; Purchase, 2004; Society of Toxi-cology, 2003).
The promotion of industry–academia interac-tions has been underway for many years. The gov-ernment has promoted these relationships throughvarious legislative acts including Stevenson-WydlerTechnology Innovation Act (1980); Bayh-DoleUniversity and Small Business Patent Act (1980);Small Business Innovation Development Act(1982); National Cooperative Research Act(1984); Federal Technology Transfer Act (1986),and the National Competitiveness TechnologyTransfer Act (1989) (see National Science Founda-tion, 2007). Because these laws, especially theBayh-Dole Act of 1980, encourage the partnershipof academia and businesses for the purpose ofbringing scientific discoveries to useful productsand services, there has been an increasing numberof studies examining university and faculty patent-ing activity (Mowery, et al., 2001). In the UnitedStates, the Federal Government retained, until1980, the intellectual property rights of anythingproduced with federal funds. Arguing that thetransfer of intellectual property ownership to thenon-Federal parties would enhance the translationof basic research to usable products and services,the Bayh-Dole Act of 1980 allowed non-government organizations ownership of the patents
developed with federal funds (Bayh-Dole Act,1980).
Effect of academia–industry relationships onfinancial CoIIn the early 1980s, some warned about the negativeconsequences of university–corporate relations(Bok, 1981), but others extolled the developmentof such relationships (Omenn, 1983). For example,Bok (1981) feared that commercialization wouldharm a university’s commitment to academic pur-suits by encouraging a search for financial gain.However, Omenn (1983) argued that commercialsupport would have no greater influence than fund-ing from wealthy individuals, foundations, orgovernment.
Although no good data exist for the early 1980s,a 1985 survey of 693 graduate students and post-doctoral fellows (Gluck, et al., 1987) showed that19% of the respondents received direct financialsupport and that another 15% worked for facultymembers receiving industrial support. Blumenthal,et al. (1986) reported that 46% of biotechnologyfirms supported academic research. In 1996, thesame group reported that over 90% of life sciencefirms supported academic research and that 28% ofthe surveyed faculty at research universitiesreceived financial support from industry. By 1999,a study of University of California, San Francisco(UCSF), faculty showed that 7.6% had personalfinancial ties with industrial sponsors, 34% werepaid for speaking engagements, 33% received con-sulting fees, and 32% were advisory board or boardof director members of commercial entities (Boydand Bero, 2000). Within this study, 89.5% of thepotential CoI disclosures involved private compa-nies or foundations, and the remainder were fundedby government agencies. Later, Boyd, et al. (2004)carried out a similar study for the multicampusUniversity of California. Seven of nine campusesparticipated. During 2001, each University of Cali-fornia campus had a CoI advisory committee thatoversaw faculty that received a total of $1.01 bil-lion in National Institutes of Health funding and$578 million in private research funding. Examin-ing disclosure records from January 1996 to June2001, 1991 disclosure forms from seven campuseswere reviewed. On average, 54.4% were for consult-ing, 37.7% for equity holdings, 14.4% for talks,12.7% for science advisory board membership, and
A review of conflict of interestLD Claxton
561
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
11.9% for membership on a board of directors.Bozeman and Gaughan (2007) showed that grantsand contracts from both industry and governmentincrease industrial involvement among universityresearchers. They also showed that the mostactively engaged with industry are faculty who arethe tenured, more senior researchers.
Similar studies have been conducted in othercountries. For example, Bourke and Butler (1999)examined the type of government funding andfound that the type of funding was less importantthan the discipline and rank of the recipient profes-sor. Benner and Sandstrom (2006) reported thatgovernment-financed research (grants and con-tracts) alters the research objectivity of academicresearchers. One Norwegian study examined theimpacts of funding from industrial sources on theinteractions between university faculty membersand industry (Gulbrandsen and Smeby, 2005).After examining questionnaire data from 1697 pro-fessors (~60% of all professors in Norway), theywere able to conclude that professors who havefinancial relationships with industry (1) do moreapplied research, (2) are more active collaboratorswith industrial and non-industrial scientists thanother professors, (3) have a higher publishing levelthan other faculty, and (4) have more patents andentrepreneurial activities.
Although the increased funding of academicresearch by industry does not substantiate (or nec-essarily imply) an increase in unethical conduct thatunduly influences the judgment of scientists respon-sible for performing and interpreting research, con-cerns have been voiced about such potential influ-ence (Behrens and Gray, 2001; Brockway andFurcht, 2006; Evans and Packham, 2003; Friedmanand Richter, 2004; Kondro, 2006; Lemmens andFreedman, 2000).
Financial CoI issues and government agenciesGovernment agencies have concerns about CoIbecause government employees, consultants, andcontractors have the potential to influence laws,regulations, and practices. For example, accordingto the U.S. Environmental Protection Agency (U.S.EPA) “A ‘conflict of interest’ is a personal interestor relationship, as defined by law or regulation,that conflicts with the faithful performance of offi-cial duty” (Office of General Counsel, 2006). Infurther defining CoI, the Office of General Council
cites Rule 18 U.S.C. §208, 5 C.F.R. 2635.502, and41 U.S.C. §423. Rule 18 U.S.C. §208 says that aperson is prohibited by a criminal statute from par-ticipating personally and substantially in an officialcapacity to influence matters in which that personor any closely related person or organization has afinancial interest. Within this rule, the responsibil-ity of persons employed by the federal governmentextends to spouses, minor children, organizationswith which one is negotiating employment, andany organization for which one serves as anemployee, officer, director, trustee, or general part-ner. Even if there is no CoI, U.S. EPA employeesare prohibited in engaging in activities, includingprocurements, that give the “appearance of con-flict” (5 C.F.R. 2635.502, 41 U.S.C. §423). TheU.S. EPA guidelines state that an employee’s CoIcan be resolved by disqualification, reassignment,change of duties, or divestiture.
Because many consultants are used for advisorycommittees, the U.S. Food and Drug Administra-tion (U.S. FDA) has CoI guidelines (currentlyunder revision) that are to be followed whenappointing advisory committee members (Foodand Drug Administration, 2007). Because theU.S. FDA must administer several laws and regu-lations that govern CoI, the draft guidance isintended to define U.S. FDA’s policy for therequirements found in 18 U.S.C 208(b)(1), 18U.S.C. 208(b)(3), 21 U.S.C. 355(n)(4), 5 CFR2640. The U.S. FDA draft guideline recognizesthat existing guidelines have grown complex andare poorly understood. As with the EPA, the U.S.FDA must determine the financial interests of theemployee; his/her immediate family members; anybusiness partner(s); any organizations for which he/she serves as officer, director, trustee, general part-ner, or employee; and any prospective employer.Although no waiver may be granted when themember’s own scientific work is involved, SpecialGovernment Employees can receive a waiver when“need for the individual’s services outweighs thepotential for a CoI created by the financial interestinvolved” (18 U.S.C. 208(b)(3)). These guidelinesattempt to address a complex set of variablesincluding investments, employment, consulting,contracts and grants, patents and royalties, plusthe level of involvement in these activities and thetype of meeting. The U.S. FDA currently imple-
A review of conflict of interestLD Claxton
562
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
menting a more stringent policy for CoI issues thanwould be dictated by the current legal framework.
Summary of financial CoI issuesThe above provides only a few examples of thedocumented financial CoI concerns faced by acade-mia, industry, and government. These concernsstem from the fear that significant financial gainhas the potential to encourage scientists (and theiremployers) to go beyond normal bias allowingfinancial gain to unduly compromise their design,conducting, analysis, and/or review of the science inwhich they are involved. Because industry is moti-vated by profits and some of the most egregiousexamples of financial CoI have involved industrialfunding, most efforts to examine financial CoI haveinvolved industry. It is important to note, however,that scientists could also be motivated to compro-mise their professional responsibilities by attempt-ing to please government agencies and private/non-profit foundations that provide financial support.
Professional and philosophical issues or concernsAtmosphere of concern due to past abusesWithin the toxicological sciences, the most docu-mented CoI issues have been associated with thetobacco industry (Baba, et al., 2005; Friedman,et al., 2005; Ong and Glantz, 2001). For example,a study funded by the National Cancer Instituteand the American Legacy Foundation (Bitton,et al., 2005) showed that components of thetobacco industry made a deliberate effort to dis-count the work of Denissenko, et al. (1996). Indus-try documents show that this work was monitoredby executives and scientists at the highest levels ofthe tobacco industry who, in turn, gave support totheir own scientists to do research that cast doubton the mechanistic research by Denissenko, et al.(Bitton, et al., 2005; Denissenko, et al., 1996). Ajournal editor with undisclosed involvements withthe tobacco industry proposed a research project toa tobacco company and then published the resultsin the editor’s journal (Bitton, et al., 2005). Whenthis was revealed to the publisher of the journal, theeditors were asked to fill out a CoI form. Whenfaced with this alternative, the editor steppeddown from his position (Bitton, et al., 2005). Thisand other abuses (Brodsky, 2007; Clabby, 2007;Clapp, et al., 2006; Dalton, 2003, 2007; Hardell,et al., 2007; Purchase, 2004; Sass, et al., 2005;
vom Saal and Hughes, 2005) demonstrate thatsome are willing to obscure competing interests inorder to advance their personal or organizationalagendas and to conceal misconduct.
Professional CoI concerns and attitudes foracademiaUniversities strive to be places of academic freedomwhere researchers are free to explore new areas,broadly publish their efforts and opinions in atimely manner, and train the next generation ofscientists. At universities, industrial support maycreate a CoI between the academic norm of openintellectual exchange and a company’s need to pro-tect proprietary information (Gluck, et al., 1987).Gluck, et al. (1987) reported that between 9% and14% of the students who received direct support orwhose faculty advisor received support experiencedpublication delays due to the sponsor. In a 1994survey of senior executives in industry, Blumenthal,et al. (1996) reported that 88% of supported stu-dents and postdoctoral fellows were required tokeep information confidential. In a separate analy-sis of the same data set, Blumenthal, et al. (1997)found that industry funding and commercializationtended to delay publication by 6 or more months.Another potential CoI issue centers on keepinginformation and data confidential beyond thetime needed to apply for a patent. In one survey,82% of the companies negotiated agreements withuniversities to keep the results of research secretuntil time needed to file an agreement and thatover half of these (or 47% of all participants)reported agreements to keep information secretbeyond the time needed to file patents (Blumenthal,et al., 1996).
Professional CoI concerns and attitudes for industryand contract laboratoriesWhether it relates to submitting data for regulatoryreview, designing and doing the research prescribedby government agencies, funding academicresearch or a host of other relationships, dealingwith CoI issues is a constant challenge for industry.A number of commentaries and papers demon-strate the challenges and viewpoints of industry(Barrow and Conrad, 2006a,b; Cassell, 2007;Duvall, 2006; LaViolette, 2007; Soule, 2007; Vage-los, 2007). For example, the industrial scientistsargue that (1) mechanisms exist to ensure thatresearch performed or funded by industry meets
A review of conflict of interestLD Claxton
563
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
high scientific standards, (2) mechanisms now existto prevent the suppression of the findings of indus-trial research, (3) the federal government does notignore or give lesser weight to scientific findingsbecause of the source of funding, and (4) all parti-cipants in scientific review panels should revealpotential biases and CoI so that balanced view-points (rather than disqualifications) can bereached (Barrow and Conrad, 2006a,b). Using pri-marily the U.S. EPA as an example, the authorspoint out that regulations require that studies beconducted in accordance with approved guidelinesespecially the Good Laboratory Practice guidelines(U.S. EPA, 2005). As a part of this requirement,the raw, quality-assured data files must be madeavailable for review. They also contend that tortliability for the suppression of adverse researchfindings is a deterrent to inappropriate actions.The authors also contend that industrial scientistsact to uphold codes of ethics recognized by theirprofession. One of Barrow and Conrad’s recom-mendations is that those involved in CoI discus-sions must distinguish between CoI and bias.
Professional CoI concerns and attitudes forgovernmentWithin government, the needs for reliance on non-government expertise, for responsiveness to thepublic’s needs, and for following agency manage-ment requirements and directives may detractfrom the diligence needed to guard against CoI.For example, Brodsky (2007) reported that theNational Toxicology Program’s (NTP) Center forthe Evaluation of Risks to Human Reproductionterminated the contract of a consulting firm respon-sible for the scientific review of bisphenol-A afterreports that the company had business ties to thechemical industry that manufactures the com-pound. Although no government scientists wereinvolved in a CoI, the public’s confidence in gov-ernment’s role to serve and protect its citizens wasdamaged. As a result, the NTP announced thatNTP’s contracting officers would be required toinsert a CoI clause in all future contracts.
Also, the potential for CoI arises from a desire toadvance professionally and in government ranks.This may entail collaborations with industrial, aca-demic, and other scientists. Although some of thesecollaborations involve no exchange of funds, manyinvolve cooperative agreements, grants, and con-
tracts. Additionally, most involve the exchange ofsamples and the expertise of the non-governmentscientist who may have biases that are not obvious.Like the scientist in academia, the government sci-entist must walk the tightrope between obtainingthe necessary resources and collaborations andguarding against even the appearance of CoI.
Professional CoI concerns and attitudes for non-profit organizations and advocacy groupsAlthough no published papers were found that spe-cifically address the CoI issues (associated with tox-icology or the life sciences) for non-profit organiza-tions and advocacy groups, they are not immune toCoI issues. Some organizations have functioned aswatchdog groups that attempt to ferret out CoIissues in industry and government (Bitton, et al.,2005; Brodsky, 2007; Goozner, 2006; Sass, 2006).Also, those who work for non-profit and watchdogorganizations are not immune to scrutiny for CoI.For example, Barrow and Conrad (2006a,b) claimthat the watchdog efforts of Sass, et al. (2005) con-stitute a CoI because they received funding fromthe Beldon Fund, which awarded the authors’employer (the Natural Resources Defense Council)a 3-year, $210,000 grant.
Methods used to control CoIBackgroundSeveral generic methods exist for avoiding CoIsituations that could lead to improper actions ordecisions. Included in these methods are divesti-ture/avoidance, recusal, third-party monitoringand evaluations, establishing a code of ethics, anddisclosure. Generally, the best way to handle CoI isto avoid the CoI even if one must divest himself/herself of an interest (e.g., stocks). With a recusal,those with a CoI are expected to abstain from deci-sions where such a conflict exists. Third-party eva-luations are used to ensure that transactions were,in fact, fair. Codes of ethics minimize problemswith CoI because they define the extent to whichsuch conflicts should be avoided and what actions(disclosure, recusal, etc.) are required to deal withspecific types of CoI. The most common methodused by scientists to deal CoI is disclosure, whichallows others to judge their objectivity. Besidesbeing a crime, in some instances, the failure to pro-vide full disclosure can affect a researcher’s reputa-tion and ability to publish.
A review of conflict of interestLD Claxton
564
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
Influence of government agencies, academies, andinternational organizationsAlthough it targeted more than scientific advisoryboards, the passage of the FACA (U.S. Congress,1972) was one of the earliest efforts to prevent CoIissues from unduly affecting decision making ingovernment. Some of the key points of the actwere (1) public disclosure of names and biographiesof potential committee members; (2) allowing pub-lic comment on such appointments; (3) attemptingto assure that no advisory committee member has aCoI that is relevant to the functions to be per-formed, unless such conflict is unavoidable and ispromptly and publicly disclosed; (4) committeememberships are fairly balanced for the functionsto be performed; and (5) all potential committeemembers declare their CoI that are relevant to thefunctions to be performed.
There are many bodies that influence public pol-icy that must rely on outside consultants for scien-tific recommendations. These organizations (e.g.,the U.S. FDA, the U.S. EPA, the National Acade-mies of Science, and the UK National Institute forHealth and Clinical Excellence) recognize the valueof preventing the improper influence of CoI. Theirpolicies can be found on their Web sites or uponrequest (Food and Drug Administration, 2007;National Institute for Health and Clinical Excel-lence, 2007; Office of General Counsel, 2006; TheNational Academies, 2003). To a variable extent,they require their own employees, special employ-ees, and consultants to disclose any organization towhich they have financial ties. In most cases, finan-cial ties include research sponsorship, equity own-ership, consulting fees, and honoraria that arerelated to the work or topic under consideration.
As another example, the WHO uses many expertconsultants to help write what are generallyregarded as definitive documents in specific healthresearch areas. CoI issues are a routine matter ofconcern because the expertise often needed is foundin a small group of individuals who (e.g., by theknowledge also needed by their employer) mayhave competing interests. WHO is, therefore, a pro-totypical organization to examine when consider-ing CoI issues. In a background document for theWHO, Boyd and Bero (2006) addressed how toobtain complete and accurate financial and othercompeting interest disclosures, how to determine
when a competing interest constitutes a CoI, howto manage a CoI, and how CoI policies can beenforced. They recognized that little research isavailable for guiding the development of disclosureforms and that open-ended formats are likely to beuninformative. WHO says that a CoI occurs when“the expert or his/her partner (a spouse or otherperson with whom s/he has a similar close personalrelationship), or the administrative unit with whichthe expert has an employment relationship, has afinancial or other interest that could unduly influ-ence the expert’s position with respect to the subjectmatter being considered.” WHO distinguishes thisfrom (1) an “apparent conflict of interest,” whichthey say exists when that expert’s interest couldresult in the expert’s objectivity being questionedby others, and (2) a “potential conflict of interest,”in which any reasonable person could be uncertainwhether or not the relationship should be reported”(World Health Organisation, 2003, 2005). TheWHO declaration identifies the types of intereststhat must be disclosed as including proprietaryinterests and patents, shares or bonds in a relatedcommercial entity, employment or consultancies,paid work or research, and grants or fellowshipsfrom a commercial entity that has an interest in thesubject-matter or work of the committee (WorldHealth Organisation, 2003).
Influences within academiaLiterature searches identified few controlled, thor-ough studies that evaluated different methods for(a) obtaining CoI disclosures, (b) deciding uponexplicit criteria for CoI, or for managing CoIwithin or (c) for managing COI within or for aca-demic organizations. In the Boyd and Bero UCSFcase study (2000) in which approximately 33% ofthe faculty reported involvement in at least one ofthe potential CoI categories surveyed, the univer-sity’s advisory committee recommended (over a19-year period) the active managing of perceivedCoI in 26% of the cases. The advisory committeerecommended that a faculty member decline fund-ing in fewer than 2% of the cases. Other forms ofmitigation recommended included disclosure offinancial interest in publications and presentations,sale of stock, resignation from a board, and the useof an oversight committee to monitor the researchactivity. Similar results were seen in a later study(Boyd, et al., 2004) expanded to include seven of
A review of conflict of interestLD Claxton
565
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
nine University of California campuses. Dependingon the campus, advisory committees recommendedthat from fewer than 10% to nearly 50% (averageof 26%) of the cases be managed for CoI. Again,denial of funding was recommended in fewer than2% of the cases. The other management toolsrecommended were essentially the same as thosein the earlier study. However, the authors didobserve that while the CoI procedures were nearlythe same on the seven campuses, each campus useddifferent CoI standards and definitions and recom-mended the use of different management strategiesfor similar cases. For each of the seven campuseswhen investigators noted a potential CoI, supple-mental forms were used to gather additional infor-mation. Because a large variation existed in theinformation gathered on these supplementalforms, some of the campuses’ advisory committeeshad relatively sparse information on which to makedecisions. This is the likely reason, according to theauthors, that some campuses had relatively lowrates of CoI management. Because each campushad different needs, experiences, types of depart-ments, and other factors, local policies had a largeinfluence on the interpretation and management ofCoI issues. The authors noted that had disclosuresbeen subject to only federal policy (i.e., incomegreater than $10,000 per year or equity ownershipgreater than 5%), two-thirds of the disclosureswould not have been reviewed by the advisorycommittees.
As many academic, governmental, and otherorganizations develop approaches to preventabuses that stem from CoI, the review and debateon appropriate management methods continue(Boyd and Bero, 2006; Cho, et al., 2000; Devine,2001; Hasselmo, 2002; Van McCrary, et al.,2000). As shown in these and other publications,most seem to look to international organizations(e.g., IARC) and governmental agencies (e.g.,U.S. FDA) for guidance in managing abuses stem-ming from CoI.
Influence of scientific societiesIn a position statement, the SOT (2003) endorsedthe policies and procedures addressing advisorycommittee issues of bias and CoI as required bylaw under FACA (U.S. Congress, 1972) and asdescribed by the National Research Council, theNational Academies of Science and Engineering,
the Institute of Medicine, and the NationalResearch Council Governing Board. SOT sees ofequal importance the use of policies and proceduresfor disclosure of CoI and the need of selection pro-cesses free from political influence and discrimina-tion. After endorsing scientific credentials, accom-plishments, and professional credibility as theprimary criteria for the appointment of advisorycommittee members, the SOT position statementsays that a number of other criteria including“source of employment and funding (past or pres-ent)” should not be used to exclude someone from ascientific advisory body. SOT guidance says thatappointees “must openly and honestly divulge anyreal or perceived CoI or potential biases that mightbe construed by others to interfere with the scien-tific credibility of the report, panel recommenda-tions, or other product of the advisory group.”
Brockway and Furcht (2006) proposed a guide-line developed with the aid of a Federation ofAmerican Societies for Experimental Biology steer-ing committee. In contrast to most other guidelines,these guidelines are not intended as organizationalguidelines but as a statement of principles that indi-vidual biomedical researchers should follow. Theyalso state that one goal was to provide academicscientists guidance on how to “address the chal-lenges that may occur due to financial arrange-ments with industry ….” Also, the guidelineencourages the individual scientist to promotetransparency and accountability. The guidelinelists 14 principles some of which are very generic(e.g., conduct scientific activities objectively andwith the highest professional standards). Some ofthe principles define specific ways that scientistsshould interact (e.g., investigators shall have accessto, and be involved in, the analysis and/or interpre-tation of all data generated in the research). Onepriority defined in the guideline says “The primaryresponsibility of full-time investigators is to theirinstitution. Outside activities shall complement,not compromise, institutional responsibilities.”This priority obviously is subservient to servingthe public good, which would be implied in “high-est professional standards.” Most of the remainingprinciples indicate to the scientist how he/sheshould view a variety of financial agreements.They conclude their paper by saying all institutionsinvolved with science, journals, and individual
A review of conflict of interestLD Claxton
566
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
investigators need to share the responsibility tomeet CoI challenges; they express the belief thatwith proper disclosure and oversight, scientistscan minimize the risks of outside collaborationswhile maximizing the benefits to the scientific com-munity and society.
Influence of science editors and publishersScientific journals have been criticized because ofCoI issues. The most common criticism is thatmany journals do not have CoI policies and/or donot appropriately request or enforce the revealingof the CoI of authors (Hardell, et al., 2007;Krimsky and Rothenberg, 2001). For example,Krimsky and Rothenberg (2001) noted that only16% of 1396 scientific journals surveyed had CoIpolicies. Additionally, Hardell, et al. (2007) citedinstances of internal CoI between journal editorsand marketing staffs.
The COPE, a forum designed to assist editors ofpeer-reviewed journals by discussing publicationissues, provides guidelines and flowcharts to editorsfor managing publication issues including CoIissues. COPE recommends that readers beinformed about not only who funded the researchbut also the “role of the funders in the research.”The flowcharts, developed after analyzing hundredsof cases from around the world, provide a practicalstep-by-step guide dealing with breaches of publica-tion ethics.
Recognizing that public trust in the credibility ofscientific articles depends in part on how well CoI ishandled during writing, peer review, and editorialdecision making, the International Committee ofMedical Journal Editors provided guidance onthis issue (ICMJE, 2006). They stated that CoIcan exist even if the relationship does not affectan individual’s scientific judgment. The committeedeclared that all participants involved in the publi-cation process for scientific papers, reviews, andeditorials must disclose all relationships that couldbe viewed as a potential CoI. In addition to expect-ing all authors to disclose financial and personalrelationships that might bias their work, theICMJE document says that sources and fundingfor individuals who provide writing assistanceshould be revealed. Recognizing that fundingfrom commercial firms, private foundations, andgovernment has the potential to bias and otherwisediscredit research, authors are directed to (1) sub-
mit only creditable research, (2) not to enter intoagreements that interfere with the disseminationdata and/or results, and (3) describe any roles thatthe funding organization had in the work. In dis-cussing the publication process, these guidelinesdescribe tasks that should be conducted by the edi-tor and editorial staff. For example, editors mustdecide what CoI information is to be publishedand when to request additional information fromthe authors and/or sponsors of the research. Editorsare also expected to choose reviewers who do nothave CoI issues with the study submitted for publi-cation, with the authors, or with the involved orga-nizations. Reviewers, themselves, are expected todisclose CoI issues for papers they are asked toreview and, if needed, to disqualify themselves.The document also advises editors to err on theside of disclosure.
In an editorial, Lehman-McKeeman and Peter-son (2003) outlined the CoI guidelines for Toxico-logical Sciences. These guidelines, similar to theprinciples espoused by ICMJE (2006), expect bothauthors and reviewers to reveal to the editor anyconflicting interests. During the review, the CoIstatements are kept confidential. Authors mustindicate all sources of funding (including directand indirect departmental, governmental, publicinterest, or institutional funds) or other interests(including professional collaboration, or competi-tion) that may be perceived to bias the research.The authors indicate these guidelines were insti-tuted to enable readers to make informed judg-ments about what to reveal.
Summary
Brodsky (2007) contends that it is unrealistic toexpect all individuals to abide by societal normsand laws in the absence of any oversight. Eventhough most scientists behave in an honorablemanner, still many cases of scientific misconductexist (Claxton, 2005a,b). CoI is an issue related tomisconduct that has been extensively discussed inscientific journals. As of July 30, 2007, the phrase‘conflict of interest’ returned 5554 references inPubMed and 2825 references in Scopus, indicatinga large interest in CoI. Such indicators of interestalso demonstrate a need for understanding whatconstitutes CoI, how one guards against the
A review of conflict of interestLD Claxton
567
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
potential negative influences of CoI, and for defin-ing the responsibilities of individual scientists, orga-nizations, societies, and journals in reducing thenegative impacts of CoI.
Although there is debate about the negativeimpacts of CoI (Behrens and Gray, 2001), thereare demonstrable cases in all areas of science,including toxicology, that show that CoI can havea negative effect on science and society. Also, thereare examples of competing interests forming an alli-ance that is beneficial not only to both parties butalso to society. In this review are examples of docu-mented CoI that negatively impacted the designing,conducting, analysis, and use of research efforts.The review also uncovered that outside influencesand collaborations can be beneficial because scien-tists receive additional financial support, increaseopportunities for collaboration, have the advantageof receiving otherwise unavailable materials,increase research opportunities, and have the likeli-hood of increased productivity. As is common inmany other controversial issues, the difficulty istwofold. First, the scientific community must estab-lish, and follow, the safeguards that prevent uneth-ical and illegal conduct. Second, laws, regulations,and guidelines should not hinder the work of thevast majority of scientists who are ethical in theirscientific actions and decisions, regardless of theirpotentially competing interests.
Competing interests (CoI) tend to generate bias,and like CoI, a bias may cause no impropriety ormay be the impetus for misconduct. However, howis it decided when CoI generates a bias that is likelyto be associated with some form of misconduct? Isit easier to see CoI and bias in another person thanin one’s self? An ancient saying is “Why do youlook at the speck of sawdust in your brother’s eyeand pay no attention to the plank in your owneye?” (Matthew 7:3). Such sayings demonstratethat throughout centuries many have found it eas-ier to see the faults (or perceived faults) of othersrather than their own faults.
In most cases of scientific misconduct involvingCoI, the CoI was kept secret, concealed, or dis-guised. Any self-serving interest can conceal CoIin an attempt to cover up scientific misconduct.However, as noted by Friedman (1992), CoI cannotbe avoided and CoI can exist without misconduct.Because misconduct usually involves concealment
and incentive (financial or otherwise), transparencyis the most often recommended tool for guardingagainst misconduct. Transparency may come inmany forms, for example, making all data avail-able, sharing of samples and methods, and disclos-ing CoI.
The issue of potential and real CoI will alwaysbe present. Unfortunately, in the toxicologicalsciences, there is a shortage of research on the prev-alence of CoI (especially harmful CoI), the majorfactors associated with CoI that lead to miscon-duct, and actions that are most effective in prevent-ing CoI from negatively impacting science. Becausebiased research may be intentional or uninten-tional, can be a matter of perception, and canhave varying levels of impact on scientific endea-vors, the scientific community continues to paymore and more attention to defining, studying,debating, and managing CoI issues.
Noting that science is a powerful and pervasiveforce for change, Wolpe (2006) called on scientiststo (1) reflect on the ends, not just the means, ofscientific work; (2) make the discussion of ethicsan active part of their profession; (3) give credenceto ethical behavior even, in rare cases, to the pointof resigning their jobs; and (4) make careful scru-tiny of their own behavior.
Acknowledgements
I want to thank those who provided review com-ments to me including Dr Dan Blazer (Duke Uni-versity, Durham, North Carolina), Dr ElizabethBoyd (University of California, San Francisco),Dr Richard Thompson (Lipscomb University,Nashville, Tennessee), and Dr Errol Zeiger (Dur-ham, North Carolina). I also thank colleagues atthe U.S. EPA who gave helpful comments, includ-ing James Allen, Linda Birnbaum, Barbara Collins,Robert MacPhail, Julian Preston, and Sarah War-ren. The author is indebted to the library staff atthe U.S. EPA, Research Triangle Park, North Car-olina, for their research assistance. The informationin this document has been funded by the U.S. EPA.It has been subjected to review by the NationalHealth and Environmental Effects Research Labo-ratory and approved for publication. Approvaldoes not signify that the contents reflect the views
A review of conflict of interestLD Claxton
568
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
of the agency, nor does mention of trade names orcommercial products constitutes endorsement orrecommendation for use.
References
Annals of Internal Medicine Editors (2004) Publishing com-mentary by authors with potential conflicts of interest:When, why, and how. Ann Intern Med 141: 73–74.
Arenson, KW (2007) Columbia settles student loan case. NewYork Times; May 31, 2007.
Baba, A, Cook, DM, McGarity, TO, Bero, LA (2005) Legis-lating “Sound science”: the role of the tobacco industry.Am J Public Health 95(Suppl. 1): S20–S27.
Barnes, DE, Bero, LA (1997) Scientific quality of originalresearch articles on environmental tobacco smoke. TobControl 6: 19–26.
Barnes, DE, Bero, LA (1998) Why review articles on thehealth effects of passive smoking reach different conclu-sions. J Am Med Assoc 279: 1566–1570.
Barrow, CS, Conrad, JW (2006a) Assessing the reliability andcredibility of industry science and scientists. EnvironHealth Perspect 114: 153–155.
Barrow, CS, Conrad, JW (2006b) Credibility of scientists: Bar-row and Conrad respond. Environ Health Perspect 114:A148.
Bayh-Dole Act (1980) Government patent policy act of 1980,public law no. 96–517, 94 stat 3015 (1980).
Behrens, TR, Gray, DO (2001) Unintended consequences ofcooperative research: impact of industry sponsorship onclimate for academic freedom and other graduate studentoutcome. Res Policy 30: 179–199.
Bekelman, JE, Li, Y, Gross, CP (2003) Scope and impact offinancial conflicts of interest in biomedical research: a sys-tematic review. J Am Med Assoc 289: 454–465.
Benner, M, Sandstrom, U (2000) Institutionalizing the triplehelix: research funding and norms in the academic system.Res Policy 29: 291–301.
Bitton, A, Neuman, MD, Barnoya, J, Glantz, SA (2005) Thep53 tumour suppressor gene and the tobacco industry:research, debate, and conflict of interest. Lancet 365:531–540.
Blumenthal, D, Campbell, EG, Anderson, MS, Causino, N,Louis, KS (1997) Withholding research results in aca-demic life science. Evidence from a national survey of fac-ulty. J Am Med Assoc 277: 1224–1228.
Blumenthal, D, Causino, N, Campbell, E, Louis, KS (1996)Relationships between academic institutions and industryin the life sciences – an industry survey. N Engl J Med334: 368–373.
Blumenthal, D, Gluck, M, Louis, KS, Wise, D (1986) Indus-trial support of university research in biotechnology. Sci-ence 231: 242–246.
Bok, DC (1981) Business and the academy. Harv Mag 83: 23–35.
Bourke, P, Butler, L (1999) The efficacy of different modes offunding research: Perspectives from Australian data onthe biological sciences. Res Policy 28: 489–499.
Boyd, EA, Bero, LA (2000) Assessing faculty financial rela-tionships with industry: a case study. J Am Med Assoc284: 2209–2214.
Boyd, EA, Bero, LA (2006) Improving the use of research evi-dence in guideline development: 4. Managing conflicts ofinterests. Health Res Policy Syst 4: 1–6 (available from:http://www.health-policy-systems.com/content/4/1/16).
Boyd, EA, Lipton, S, Bero, LA (2004) Implementation offinancial disclosure policies to manage conflicts of inter-est: how seven university of California campuses deal withtheir research relationships. Health Aff 23: 206–214.
Bozeman, B, Gaughan, M (2007) Impacts of grants and con-tracts on academic researchers’ interactions with industry.Res Policy 36: 694–707.
Brockway, LM, Furcht, LT (2006) Conflicts of interest in bio-medical research – the FASEB guidelines. FASEB J 20:2435–2438.
Brodsky, R (2007) Don’t ask, don’t tell. Gov Exec 39: 18–19.Callaham, ML (2003) Journal policy on ethics in scientific
publication. Ann Emerg Med 41: 82–89.Campbell, EG, Louis, KS, Blumenthal, D (1998) Looking a
gift horse in the mouth: corporate gifts supporting lifesciences research. J Am Med Assoc 279: 995–999.
Cassell, GH (2007) Interactions of the public and private sec-tors in drug development: boundaries to protect scientificvalues while preserving innovation. Cleve Clin J Med 74 :S45–S48.
Center for Science in the Public Interest and EnvironmentalWorking Group (2004) CSPI, environmental workinggroup challenge two scientists on EPA panel. Availableat: http://cspinet.org/integrity/press/200412091.html.
Check, E (2007) California campuses resist industry restric-tions. Nature 448: 394–395.
Chisolm III, GM (ed) (2007) Proceedings of a National Dia-logue on Biomedical Conflicts of Interest and InnovationManagement. Suppl. 2 to vol. 74, Cleveland Clinic. Avail-able at: http://www.ccjm.org/toc/COI.htm [accessed30.07.07].
Cho, MK, Bero, LA (1996) The quality of drug studies pub-lished in symposium proceedings. Ann Intern Med 124:495–489.
Cho, MK, Shohara, R, Schissel, A, Rennie, D (2000) Policieson faculty conflicts of interest at US universities. J AmMed Assoc 284: 2203–2208.
Clabby, C (2007) Letter questions ethics of institute head: Sen-ator cites outside work, ties to Duke. News and Observer[newspaper]. Jun 29, 2007 05:53 AM. Available at: http://www.newsobserver.com/news/health_science/story/621026.html [accessed 05.07.07].
Clapp, R, Hoppin, P, Kriebel, D (2006) Erosion of the integ-rity of public health science in the USA. Occup EnvironMed 63: 367–368.
Claxton, LD (2005a) Scientific authorship, part 1: a windowinto scientific fraud? Mutat Res 589: 17–30.
A review of conflict of interestLD Claxton
569
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
Claxton, LD (2005b) Scientific authorship, part 2: history,recurring issues, practices, and guidelines. Mutat Res589: 31–45.
Committee on Publication Ethics (COPE) (2003) The COPEReport 2003: Annual Report of the Committee on Publi-cation Ethics. Available at http://www.Publicationethics.Org.Uk/reports/2003. London, UK: BMJ Books, BMAHouse; 2003.
Committee on Publication Ethics (COPE) (2007) Guidelineson good publication practice 2003. Available at: http://www.publicationethics.org.uk/[accessed 07.08.07].
Dalton, R (1999) Berkeley dispute festers over biotech deal.Nature 399: 5.
Dalton, R (2003) Berkeley accused of biotech bias as ecologistis denied tenure. Nature 426: 591–594.
Dalton, R (2007) Berkeley’s energy deal with BP sparksunease. Nature 445: 688–689.
Dearfield, KL, Stack, HF, Quest, JA, Whiting, RJ, Waters,MD (1993) A survey of EPA/OPP and open literaturedata on selected pesticide chemicals tested for mutagenic-ity. I. Introduction and first ten chemicals. Mutat Res297: 197–233.
Denissenko, MF, Pao, A, Tang, M, Pfeifer, GP (1996) Prefer-ential formation of benzo[a]pyrene adducts at lung cancermutational hotspots in p53. Science 274: 430–432.
Devine, J (2001) Has there been a corporate takeover of EPAscience? [Available at: http://www.Insideepa.Com/secure/docnum.Asp?F = epa_2001.Ask&docnum = 2001_11276]Risk Policy Report 8: 35–38.
Doll, R (1998) Effects of exposure to vinyl chloride. An assess-ment of the evidence. Scand J Work Environ Health 14:61–78.
Duvall, DG (2006) Conflict of interest or ideological divide:The need for ongoing collaboration between physiciansand industry. Curr Med Res Opin 9: 1807–1812.
Evans, GR, Packham, DE (2003) Ethical issues at theuniversity-industry interface: a way forward? Sci EngEthics 9: 3–16.
Fields, N, Chapman, S (2003) Chasing Ernst L Wynder:40 years of Philip Morris’ efforts to influence a leadingscientist. J Epidemiol Community Health 57: 571–578.
Food and Drug Administration (2007) Draft guidance for thepublic, FDA advisory committee members, and FDAstaff on procedures for determining conflict of interestand eligibility for participation in FDA advisory commit-tees: Draft guidance. U.S. Department of Health andHuman Services - Food and Drug Administration 2007.Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/07d-0101-gdl0001.pdf [accessed 27.06.07].
Friedman, PJ (1992) The troublesome semantics of conflict ofinterest. Ethics Behav 2: 245–251.
Friedman, LC, Daynard, RA, Banthin, CN (2005) Howtobacco-friendly science escapes scrutiny in the court-room. Am J Public Health 95: S16–S20.
Friedman, LS, Richter, ED (2004) Relationship between con-flicts of interest and research results. J Gen Intern Med 19:51–56.
Friedman, L, Richter, ED (2005) Conflicts of interest and sci-entific integrity. Int J Occup Environ Health 11: 205–206.
Fugh-Berman, A (2005) The corporate coauthor. J Gen InternMed 20: 546–548.
Garne, D, Watson, M, Chapman, S, Byrne, F (2005) Environ-mental tobacco smoke research published in the journalIndoor and Built Environment and associations with thetobacco industry. Lancet 365: 804–809.
George, G, Zahra, SA, Wood, DR (2002) The effects ofbusiness-university alliances on innovative output andfinancial performance: a study of publicly traded biotech-nology companies. J Bus Venturing 17: 577–609.
Gluck, ME, Blumenthal, D, Stoto, MA (1987) University–industry relationships in the life sciences: implicationsfor students and post-doctoral fellows. Res Policy 16:327–336.
Gold, JL (2006) Conflict over conflicts of interest: an analysisof the new NIH rules. J Law Med Ethics 34: 105–110.
Goozner, M (2004) Unrevealed: non-disclosure of conflicts ofinterest in four leading medical and scientific journals.Integrity in Science. July 12, 2004. Available at: http://cspinet.org/new/pdf/unrevealed_final.pdf2004:16[accessed 01.07.07].
Goozner, M (2006) Credibility of scientists: industry versuspublic interest. Environ Health Perspect 114: A147[author reply A148].
Gulbrandsen, M, Smeby, J-C (2005) Industry funding and uni-versity professors’ research performance. Res Policy 34:932–950.
Hardell, L, Walker, MJ, Walhjalt, B, Friedman, LS, Richter,ED (2007) Secret ties to industry and conflicting interestsin cancer research. Am J Ind Med 50: 227–233.
Hasselmo, N (2002) Individual and institutional conflict ofinterest: Policy review by research universities in theUnited States. Sci Eng Ethics 8: 421–427.
Hutton, WL, Massey, A (2006) Professional ethics and publicservice: Can professionals serve two masters? PublicMoney Manage 26: 23–30.
ICMJE (2006) Uniform requirements for manuscripts submit-ted to biomedical journals: writing and editing for bio-medical publication. International Committee of MedicalJournal Editors 2006. Available at: http://www.icmje.org/[accessed 08.08.07].
Kenney, M (1987) The ethical dilemmas of university-industrycollaborations. J Bus Ethics 6: 127–135.
Kodish, E, Murray, T, Whitehouse, P (1996) Conflict of inter-est in university-industry research relationships: Realities,politics, and values. Acad Med 71: 1287–1290.
Kondro, W (2006) Conflicts cause FDA to review advisorycommittees. Can Med Assoc J 175: 23–24.
Krimsky, S, Rothenberg, LS (2001) Conflict of interest policiesin science and medical journals: editorial practices andauthor disclosures. Sci Eng Ethics Behav 7: 205–218.
Labaton, S (2007) Nominee to head consumer agency with-draws. New York Times; May 23, 2007.
LaViolette, PA (2007) Medical devices and conflict of interest:unique issues and an industry code to address them. CleveClin J Med 74 : S26–S28.
A review of conflict of interestLD Claxton
570
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from
Lehman-McKeeman, L, Peterson, RE (2003) Guidelines gov-erning conflict of interest. Toxicol Sci 72: 183–184.
Lemmens, T, Freedman, B (2000) Ethics review for sale? Con-flict of interest and commercial research review boards.Milbank Q 78: 547–584.
Lexchin, J, Bero, LA, Djulbegovic, B, Clark, O (2003) Phar-maceutical industry sponsorship and research outcomeand quality: systematic review. Br Med J 326: 1167–1170.
Markowitz, G, Rosner, D (2002) Deceit and denial: the deadlypolitics of industrial pollution. Berkeley, CA: University ofCalifornia Press. pp. 408.
Matthew 7:3. The Holy Bible (New International Version).Maurissen, JP, Gilbert, SG, Sander, M, Beauchamp, TL,
Johnson, S, Schwetz, BA, Goozner, M, Barrow, CS(2005) Workshop proceedings: managing conflict of inter-est in science. A little consensus and a lot of controversy.Toxicol Sci 87: 11–14.
Mowery, D, Nelson, RR, Sampat, BN, Ziedonis, AA (2001)The growth of patenting and licensing by U.S. Universi-ties: an assessment of the effects of the Bayh-Dole act of1980. Res Policy 30: 99–119.
National Institute for Health and Clinical Excellence (2007)Code of practice for declaring and dealing with conflictsof interest. Available at: http://www.nice.org.uk/page.aspx?o = 431882 [accessed 27.06.07].
National Science Foundation (2007) Principal federal legisla-tion related to cooperative technology programshttp://www.nsf.gov/statistics/seind98/c4/tt04-08.htm [accessed11.07.07].
Nature Editorial (2007) California dreaming. Nature 448: 388–388.
Newman, A (2007) To sell Brooklyn, borough leader took freetrip on cruise ship. New York Times; May 26, 2007.
Office of General Counsel (2006) Ethics resource guide.Washington, D.C.: U.S. Environmental ProtectionAgency.
Omenn, GS (1983) University-corporate relations in scienceand technology: an analysis of specific models. In:Langfelt, T, Hackncy, F, Fishman, A, Golowsky, H(eds), Partners in the Research Enterprise: Universities-Corporations in Science and Technology. Philadelphia,PA: University of Pennsylvania Press.
Ong, EK, Glantz, SA (2001) Constructing “Sound science”and “Good epidemiology”: tobacco, lawyers, and publicrelations firms. Am J Public Health 91: 1749–1757.
Pronin, E, Gilovich, T, Ross, L (2004) Objectivity in the eye ofthe beholder: divergent perceptions of bias in self versusothers. Psychol Rev 111: 781–799.
Purchase, IFH (2004) Fraud, errors and gamesmanship inexperimental toxicology. Toxicology 202: 1–20.
Rumsey, TS (1999) One editor’s views on conflict of interest. JAnim Sci 77: 2379–2383.
Samet, JM, Burke, TA (2001) Turning science into junk: thetobacco industry and passive smoking. Am J PublicHealth 91: 1742–1744.
Sass, JB, Castleman, B, Wallinga, D (2005) Vinyl chloride. Acase study of data suppression and misrepresentation.Environ Health Perspect 113: 809–812.
Sass, J (2006) Credibility of scientists: conflict of interest andbias. Environ Health Perspect 114: A147–A148 [authorreply A148].
Sengupta, S (2007) Sri Lanka human rights panel is criticized.New York Times; June 11, 2007.
Smith, EA (2007) ‘It’s interesting how few people die fromsmoking’: tobacco industry efforts to minimize risk anddiscredit health promotion. Eur J Public Health 17: 162–170.
Society of Toxicology (2003) SOT position statement on theappointment and participation of scientists on peer reviewpanels and scientific advisory boards, Society of Toxicol-ogy 2003. Available at: http://www.toxicology.org/ai/asot/AdvisoryBoard.asp [accessed 09.05.07].
Soule, E (2007) Managing ethical performance in organiza-tions: insights from the corporate world. Cleve Clin JMed 74: S73–S76.
Stark, A (2000) Conflict of interest in American public life Bos-ton. MA: Harvard University Press. pp. 384.
Stark, A (2006) Canada’s upside-down world of public-sectorethics. Res Public Policy Anal Manage 14: 109–134.
Steinbrook, R (2004) Conflicts of interest at the NIH – resolv-ing the problem. N Engl J Med 351: 955–957.
Sugarman, SD (2005) Conflicts of interest in the roles of theuniversity professor. Theoretical Inquiries in Law 6: 255–275.
The National Academies (2003) Policy on committee composi-tion and balance and conflicts of interest for committeesused in the development of reports. Washington, D.C.:The National Academies.
Thompson, DF (1993) Understanding financial conflicts ofinterest. N Engl J Med 329: 573–576.
U.S. Congress (1972) Federal advisory committee act [FACA]5 U.S.C. app., As Amended; 1972.
U.S. EPA (2005) Good laboratory practice standards. 40 cfr160. Washington, DC: U.S. Environmental ProtectionAgency.
Vagelos, PR (2007) Innovation and industry-academia interac-tions: where conflicts arise and measures to avoid them.Cleve Clin J Med 74 : S12–S13.
Van McCrary, S, Anderson, CB, Jakovljevic, J, Khan, T,McCullough, LB, Wray, NP, Brody, BA (2000) Anational survey of policies on disclosure of conflicts ofinterest in biomedical research. N Engl J Med 343:1621–1626.
vom Saal, FS, Hughes, C (2005) An extensive new literatureconcerning low-dose effects of bisphenol A shows theneed for a new risk assessment. Environ Health Perspect113: 926–933.
Wolpe, PR (2006) Reasons scientists avoid thinking aboutethics. Cell 125: 1023–1025.
World Health Organisation (2003) Guidelines for WHOguidelines, Report No. EIP/GPE/EQC/2003.1.
World Health Organisation (2005) Draft guidelines for decla-ration of interest (WHO experts).
Yach, D, Bialous, SA (2001) Junking science to promotetobacco. Am J Public Health 91: 1745–1748.
A review of conflict of interestLD Claxton
571
© 2007 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution. at US Environmental Protection Agency on June 20, 2008 http://tih.sagepub.comDownloaded from