Title: Conflicts of interest for medical publishers and editors: Protecting the integrity of scientific scholarship
Abstract: Competition of interest may exist at all levels in the medical publication process. Ensuring the integrity of scientific scholarship involves protecting editorial independence, promoting the use of scientific arbitration boards, promoting transparency throughout all stages of publication, and protecting the relationship between the publisher and its editors through an effective legal framework. It is incumbent upon the publisher, editors, authors, and readers to ensure that the highest standards of scientific scholarship are upheld. Doing so will help reduce fraud and misrepresentation in medical research and increase the trustworthiness of landmark findings in science. Competition of interest may exist at all levels in the medical publication process. Ensuring the integrity of scientific scholarship involves protecting editorial independence, promoting the use of scientific arbitration boards, promoting transparency throughout all stages of publication, and protecting the relationship between the publisher and its editors through an effective legal framework. It is incumbent upon the publisher, editors, authors, and readers to ensure that the highest standards of scientific scholarship are upheld. Doing so will help reduce fraud and misrepresentation in medical research and increase the trustworthiness of landmark findings in science. Competition of interest issues have received much attention from the government, media, and scientific communities recently. Of particular interest has been scientific inquiry in which financial conflicts, sometimes combined with incomplete or improper disclosure, lead to the perception (or reality) that the study results may be biased or inaccurate.1Heckman J.D. Retractions.J Bone Joint Surg Am. 2009; 91 (Retractions in J Bone Joint Surg Am 2005;87:536-42; J Bone Joint Surg Am 2007;89:1343-8): 965Crossref PubMed Google Scholar, 2Kuklo T.R. Groth A.T. Anderson R.C. Frisch H.M. Islinger R.B. Recombinant human bone morphogenetic protein-2 for grade III open segmental tibial fractures from combat injuries in Iraq.J Bone Joint Surg Br. 2008; 90 (Retraction in J Bone Joint Surg Br 2009;91:285-6): 1068-1072Crossref PubMed Scopus (146) Google Scholar, 3Reuben S.S. Ekman E.F. The effect of cyclooxygenase-2 inhibition on analgesia and spinal fusion.J Bone Joint Surg Am. 2005; 87 (Retraction in J Bone Joint Surg Am 2009;91:965): 536-542Crossref PubMed Scopus (96) Google Scholar, 4Scott J. Withdrawal of a paper.J Bone Joint Surg Br. 2009; 91: 285-286Crossref PubMed Scopus (11) Google Scholar Additionally, past abuse of federal health care funds has led to fines and incarceration for the most egregious offenders.5Sox H.C. Rennie D. Research misconduct, retraction, and cleansing the medical literature: lessons from the Poehlman Case.An Intern Med. 2006; 144: 609-613Crossref PubMed Scopus (155) Google Scholar Competition of interest and errors in their disclosure range from the innocent to the criminal. In some cases, the conflicting interest may interfere with the impartiality and integrity of the scientific endeavor. For authors, this may mean failure to disclose a financial conflict in the hopes that publication of a particular study will bring fortune.6Krimsky S. Rothenberg L.S. Financial interest and its disclosure in scientific publications.JAMA. 1998; 280: 225-226Crossref PubMed Scopus (61) Google Scholar, 7Perlis R.H. Perlis C.S. Wu Y. Hwang C. Joseph M. Nierenberg A.A. Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry.Am J Psychiatry. 2005; 162: 1957-1960Crossref PubMed Scopus (236) Google Scholar In other instances, grant support by industry partners has been associated with the publication of proindustry results.8Bhandari M. Busse J.W. Jackowski D. Montori V.M. Schünemann H. Sprague S. et al.Association between industry funding and statistically significant pro-industry findings in medical and surgical randomized trials.CMAJ. 2004; 170: 477-480PubMed Google Scholar Such conflicts of interest between an author and the published study are discussed elsewhere in this Journal and the medical literature. A topic that has received far less attention is the potential for serious conflicts of interest between editors, contributing authors, the publisher, and advertisers (Fig 1) .9Committee on Publication EthicsGuidelines on good publication practice The COPE Report.http://www.publicationethics.org.uk/about/Date: 2003Google Scholar, 10Lederberg J. Communication as the root of scientific progress.Scientist. 1993; : 10-14Google Scholar, 11Rennie D. The ethics of medical publication.Medial J Aust. 1979; 2: 409-412PubMed Google Scholar While authors are primarily interested in their manuscript, editors of major journals routinely interface with a much broader group and, therefore, may be more susceptible to bias and potential influence. For example, advertisers who wish to have a particular ad incorporated into a journal issue may approach one of the editors of a journal. Hypothetically, that editor may be more inclined to accept a study that deals with a product being sold by the advertiser, or reject an article that discusses negative findings about the product. Editors may then potentially coerce the publisher to place the ad next to the favorable study. These paid placements may lead to greater profits for the journal and some reward for the editor. The peer-review process thereby breaks down and the standards of scientific scholarship are sacrificed for material gain. This article discusses these potential conflicts of interest from the publishing aspect of medical scholarship: editors and publishers must be as responsible as authors to promote and protect the integrity of the scientific process. As the final gateway in the publishing process, editors in particular must be vigilant against these trespasses and ensure that the content of medical publications is entirely independent of all personal, institutional, and corporate influence. This responsibility can be achieved by protecting editorial independence, promoting the use of a scientific arbitration board for serious disputes, promoting transparency throughout all stages of publication, and taking advantage of an effective legal framework via contracts and agreements to protect scientific scholarship. By overseeing the process of peer-review, editors influence the selection of reviewers and adjudicate feedback given to the authors. Bias within this process may make a manuscript more or less likely to be accepted. In other cases, editors who have a research interest closely aligned to a particular manuscript will have advanced access to unpublished data and findings that may influence their work. This may lead to an unfair advantage in concurrent grant applications, or even outright rejection of the manuscript to preserve their scientific advantage. The currency of academicians is the number and quality of peer-reviewed publications: they promote their rise in academic channels, help obtain grant funding, and gain influence. As the key decision makers on articles, editors influence the careers of their authors by determining the fate of their submissions. Accepting or rejecting such articles can thereby influence opportunities to obtain grant funding and academic advancement.12Asai T. Shingu K. Ethical considerations in anaesthesia journals.Anaesthesia. 1999; 54: 108-109Crossref PubMed Scopus (2) Google Scholar, 13Bevan J.C. Ethical behavior of authors in biomedical journalism.Ann Royal Coll Phys Surg Canada. 2002; 35: 81-85PubMed Google Scholar In addition to working with authors, editors also interact closely with the publisher. Print deadlines, manuscript requirements, copyright waivers, disclosures, author agreements, copyediting, proofing, and many more details continuously influence the relationship between editors and publishers. Finally, editors also have the opportunity to interface with advertisers. It is likely that the business and professional affiliates of editors will be aware of their role in an influential journal.14Bero L.A. Galbraith A. Rennie D. The publication of sponsored symposiums in medical journals.N Engl J Med. 1992; 327: 1135-1140Crossref PubMed Scopus (102) Google Scholar, 15Bero L.A. Rennie D. Influences on the quality of published drug studies.Int J Technol Assess Health Care. 1996; 12: 209-237Crossref PubMed Scopus (173) Google Scholar These relationships create a potential conflict of interest resulting from inappropriate influence over the peer-review process, including promotion of relevant products within journal articles, favoring manuscripts that support the advertizer, advance distribution of journal issue contents to afford the opportunity for simultaneous advertising or other unfair advantages.16Rennie D. What is research misconduct?.in: Wells F. Farthing M. Fraud and misconduct in biomedical research. Royal Society of Medicine Press, London2008: 29-51Google Scholar, 17Rennie D. Gunsalus C.K. Scientific misconduct New definition, procedures, and office—perhaps a new leaf.JAMA. 1993; 269: 915-917Crossref PubMed Scopus (29) Google Scholar Publishers of medical journals have a vested financial interest in the journal. They are charged with providing an instrument through which scientific findings are communicated to an educated audience. Publishers work directly with advertisers to ensure that their journal remains sustainable. Through their financial resources, they are able to provide administrative support for the journal while continuing to develop their circulation and content. Publishers enable authors, editors, and readers to communicate by providing a neutral platform. In today's digital workflow, this streamlines manuscript submission, expedites peer-review, and leads to a faster turnover time while increasing convenience for all involved parties. Once a manuscript has been accepted for publication, the publisher completes the copyediting process and converts the manuscript into the final published form. If editors determine which articles should be published, the publisher determines how they will be printed and distributed. Publishers may coerce editors to accept or reject certain manuscripts, especially if they are not congruent with other interests the publisher may have.18Gottlieb S. New E. Journal's publisher in conflict of interest dispute.BMJ. 1999; 319 (1220B)Google Scholar Certain design or printing constraints may affect the particular arrangement or appearance of an article. Publishers work closely with their editors to maintain the scientific and ethical integrity of the journal. However, this relationship also creates the opportunity to influence whether certain manuscripts are accepted or rejected. Depending on the particular constraints of the journal, publishers may pressure editors to reject manuscripts that discuss controversial topics, publish findings that are counter to the financial interests of the publisher, or do not meet the particular design requirements of the journal. Publishers are also charged with seeking opportunities to increase their readership and overall circulation. For many journals, greater circulation leads to greater prominence and financial gain. The selection and placement of advertising, articles, and various design elements may influence this readership. Particularly controversial articles may lead to a decline in circulation or negative media attention. Publishers who are part of companies that conduct business in other areas of medicine may be particularly pushed to engage editors over certain articles.19Eggertson L. Lancet publisher to sell arms business.CMAJ. 2007; 177: 242PubMed Google Scholar These complex relationships between authors, editors, publishers, advertisers, and readers create the opportunity for conflicts of interest that threaten the integrity of scientific scholarship. These conflicts extend well beyond the scientific and ethical issues that exist between authors and their manuscripts. Potential abuse of these relationships introduces a variable for which there has not yet been a significant conversation in the medical literature. There remains some debate as to whether the peer-review process should be double-blind, single-blind, or if it should be blinded at all.20King C. McGuire D. Longman A. Carroll-Johnson R. Peer review, authorship, ethics, and conflict of interest.J Nurs Scholarsh. 1997; 29: 163-167Crossref Scopus (32) Google Scholar, 21Rennie D. Anonymity of Reviewers.Cadiovsc Researc. 1994; 28: 1142-1143Google Scholar, 22Ingelfinger F.J. Peer review in biomedical publication.Am J Med. 1974; 56: 686-692Abstract Full Text PDF PubMed Scopus (116) Google Scholar, 23Jefferson T. Alderson P. Wager E. Davidoff F. Effects of editorial peer review: a systematic review.JAMA. 2002; 287: 2784-2786Crossref PubMed Scopus (219) Google Scholar, 24Kassirer J.P. Campion E.W. Peer review: crude and understudied, but indispensable.JAMA. 1994; 272: 96-97Crossref PubMed Scopus (174) Google Scholar Several major journals have opted to forgo blinding and instead keep all authors, affiliations, and manuscript reviewers out in the open. By publishing this information, any potential conflicts of interest are made available for external review. The rationale is that any disclosures or conflicts between editors and the manuscripts they review will be avoided. While the results thus far have been satisfactory,23Jefferson T. Alderson P. Wager E. Davidoff F. Effects of editorial peer review: a systematic review.JAMA. 2002; 287: 2784-2786Crossref PubMed Scopus (219) Google Scholar, 25Groves T. Is open peer review the fairest system? Yes.BMJ. 2010; 341: c6424Crossref PubMed Scopus (37) Google Scholar open review does not solve the issue of editors potentially gaining benefit in the future via a quid pro quo transaction with the authors in future academic endeavors.26Khan K. Is open peer review the fairest system? No.BMJ. 2010; 341: c6425Crossref PubMed Scopus (34) Google Scholar Further, there may be some pressure to accept manuscripts from influential and powerful authors, as rejection of a manuscript or negative feedback may sever relationships, lead to animosity, or repercussions. Double-blinding the peer-review process reduces the likelihood of such quid pro quo transactions and also promotes more complete positive and negative feedback to authors. To maintain the fidelity of this process, this double-blind peer-review should be supervised by the Editor-in-Chief. The primary role of the Editor-in-Chief should be to ensure that the appropriate editors and reviewers will receive the manuscript for review, and that these reviewers will not be in a position to unduly benefit or influence the work at hand. The reviewers will serve as a system of checks and balances, as they will ultimately become aware of the identities of the authors whose work they reviewed should it reach the publication stage. This arrangement avoids self-policing, preserves the integrity of peer-review, and reduces bias by editors and authors. By assigning manuscripts through the Editor-in-Chief, reviewers with a closely aligned research interest or other corruptible conflict of interest are excluded immediately. Limitations of this process must be recognized: in many cases authors and institutions can be recognized by the manuscript content, the blinding process is not watertight, and new findings can still be poached even if the authors' identities are not known. Editors are in a unique position to be influenced by a variety of competing interests. Editors have a responsibility to preserve the integrity of scientific scholarship through maintenance of the peer-review process and uphold high ethical standards. These interests may occasionally compete with desires manifest by the publisher, societal sponsors, advertisers, authors, and readers. To ensure that editors are able to make their decisions without significant coercion, they should be protected by a legal framework that preserves their independence within the physical limitations of the journal (Fig 2) .27Davis R. Mullner M. Editorial independence at medical journals owned by professional associations: a survey of editors.Sci Eng Ethics. 2002; 8: 513-528Crossref PubMed Scopus (28) Google Scholar, 28Rennie D. Guarding the guardians: a conference on editorial peer review.JAMA. 1986; 256: 2391-2392Crossref PubMed Scopus (85) Google Scholar, 29Cooper R.J. Gupta M. Wilkes M.S. Hoffman J.R. Conflict of interest disclosure policies and practices in peer-reviewed biomedical journals.J Gen Intern Med. 2006; 21: 1248-1252Crossref PubMed Scopus (79) Google Scholar Furthermore, their duty to the high standards of scientific scholarship should be protected by limiting their role in dealing with entities that may influence the peer-review process. Editors should not have any role in recruiting, selecting, or placing advertising within a journal. This entire process should be controlled by the publisher (who in turn has no influence over scientific content of the journal). Removing editors from this role entirely mitigates the potential for biasing the selection of manuscripts and potentially inappropriate benefits from working with industry partners in the capacity of an editor.30Vlassov V.V. Is content of medical journals related to advertisements? Case-control study.Croat Med J. 2007; 48: 786-790Crossref PubMed Scopus (7) Google Scholar In addition, the publication's advertising staff should not have advance knowledge of the content of a journal issue to eliminate the opportunity of influencing advertising content. A legal contract should be in place between the publisher and the editors that guarantees their independence unless there are exceptional circumstances. Editors should be appointed for a fixed term and should be permitted to make independent decisions regarding the selection, inclusion, and arrangement of articles within the design limitations of the journal. While the publisher is inherently responsible for the stylistic and formatting conditions, the final layout of an article should be done in conjunction with the editors and authors. Such a legal framework also protects editors from being influenced by societal sponsors and demands that the publisher may have from time to time. The inclusion of certain articles should be left entirely up to the editors in conjunction with the peer-review process. Publishers provide a valuable instrument to communicate important scientific findings; as part of the separation of powers, editors should be the ones who determine what those findings will be. Occasionally, there will be serious challenges to the guiding principles of a journal. Despite the precautions that major journals take today against fraud and corruption, no one is immune from a perversion of the scientific process. Major conflicts of interest, ethical dilemmas, and other major issues should be resolved by a scientific arbitration board composed of editors and publishers (Fig 2). If pertinent, authors and readers should be invited to participate in the proceedings. Such a board serves as a final method of checks and balances against the publisher and editors; the decisions of this board should be binding upon all parties. Such a board provides a unique opportunity to confront authors involved with plagiarism, data fabrication, and other major violations of scientific trust. It provides a forum to challenge editors who may have been involved in questionable decision-making or who may have trespassed upon the ethical and scientific standards of the journal. It also serves to notify the publisher, advertisers, and readers of any potential breaches in scientific scholarship. By incorporating all of the parties with a vested interest in such a board, it becomes capable of dealing with even the most challenging issues that face a journal. The Editor-in-Chief serves as the public face of the journal and the final authority on all its scientific matters. Yet, even they may be placed in positions where a conflict of interest exists, either between them and a paper under review, with other editors, or even with the publisher. Objectivity is the key to maintaining high standards of scientific scholarship; if such objectivity of an Editor-in-Chief is compromised, he must recuse himself from the decision-making process and assign the task to a managing editor. Managing editors should be appointed such that their potential conflicts of interests are not similar to that of the Editor-in-Chief so that they can help resolve situations from which the Editor-in-Chief must be recused. In situations where the conflict of interest cannot be resolved by the managing editor, important decisions should then be undertaken by the scientific arbitration board. The key to protecting the publication process is to make all major decisions transparent. Hasty decisions made when conflicts of interest are present can present serious legal issues due to the financial and societal repercussions that can occur. In 2006, a prominent South Korean scientist was indicted for embezzlement and scientific fraud and sentenced to a short prison term.31Cyranoski D. Hwang W.S. Convicted, but not of fraud.Nature. 2009; 461: 1181Crossref PubMed Scopus (11) Google Scholar Dr Hwang made headlines when he published two papers in Science that described his research on patient-specific stem-cells derived from embryos that could be used for stem cell transplants.32Hwang W.S. Ryu Y.J. Park J.H. Park E.S. Lee E.G. Koo J.M. et al.Evidence of a pluripotent human embryonic stem cell line derived from a cloned blastocyst.Science. 2004; 303: 1669-1674Crossref PubMed Scopus (575) Google Scholar, 33Hwang W.S. Roh S.I. Lee B.C. Kang S.K. Kwon D.K. Kim S. et al.Patient-specific embryonic stem cells derived from human SCNT blastocysts.Science. 2005; 308: 1777-1783Crossref PubMed Scopus (363) Google Scholar This past year, a prominent researcher at Harvard was found guilty of eight counts of scientific misconduct. A paper in a prominent psychology journal was retracted, and there is an ongoing investigation by the US Attorney's Office for the District of Massachusetts.34Miller G. Harvard dean confirms misconduct in Hauser investigation.ScienceInsider. Aug 20, 2010; Google Scholar In November 2010, a prominent cancer researcher at Duke University resigned from his post following the retraction of an important paper and cessation of clinical trials that were based on questionable data.35Hsu D.S. Balakumaran B.S. Acharya C.R. Vlahovic V. Walters K.S. Garman K. et al.Retraction Pharmacogenomic strategies provide a rational approach to the treatment of cisplatin-resistant patients with advanced cancer.J Clin Oncol. 2007; 25 (J Clin Oncol 2010;28:5229): 4350-4357Crossref PubMed Scopus (84) Google Scholar, 36Tracer Z. Doherty T. Updated: Anil Potti, Duke Cancer Researcher Accused of Misconduct, Resigns.The Chronicle (Duke). Nov 19, 2010; Google Scholar Questions regarding his credentials have also led to an investigation from the American Cancer Society as to whether grants obtained by that society were under false pretenses.36Tracer Z. Doherty T. Updated: Anil Potti, Duke Cancer Researcher Accused of Misconduct, Resigns.The Chronicle (Duke). Nov 19, 2010; Google Scholar Major conflicts of interest may be manifest in extreme ways that violate local, state, or federal statutes that may be punishable by fines and/or incarceration. In USA vs Poehlman (2006), Dr Poehlman made a plea bargain with prosecutors to serve 1 year and a day in jail for fabricating data in 10 different papers and falsifying grant applications to the National Institutes of Health (NIH) related to hormone replacement therapy for menopause.37USA v. Poehlman. 2:05-cv-00066-wks. (2005) Obtained from PACER database on Jan 1, 2011.Google Scholar While making simple mistakes is unlikely to lead to an allegation of scientific misconduct (cf NIH Office of Research Integrity misconduct statement), intentional data fabrication, fraud, and embezzlement are likely to get the attention of authorities. As these issues take on more importance, it is incumbent upon editors and publishers to identify instances of scientific misconduct prior to publication, and to more aggressively handle cases as they come to light. For instance, communicating with all authors of a manuscript instead of just the submitting author can help ensure that all authors are aware of the nature and content of the publication. Having access to the original data, particularly for landmark publications, can help foster scientific oversight; this is particularly noteworthy in our time given our ready access to rich media over the Internet. Simultaneously publishing such original data online in conjunction with the paper can help eliminate doubt while furthering scientific scholarship. Finally, to avoid ambiguity when these issues arise, a concerted effort between the publisher and its editors should be made to publish disclosures of conflicts of interest, conflict of interest policies, a statement on the standards of scientific scholarship, and so forth. There are also legal issues that can exist between the publisher and its editors. Relationships between these two entities should be protected in the form of a contract. Such a written statement also helps to clarify the responsibilities of the two entities, and promotes transparency in this important relationship. Such a legal framework protects both publishers and editors; an effective policy will not hinder the free and open exchange of ideas nor impede scientific scholarship. Potential conflicts of interest exist at all stages in publishing. The highest standards of scientific scholarship should be upheld, but readers, authors, editors, and publishers are all equal partners in this endeavor. By instituting transparency with regard to peer-review, decision-making, and internal journal processes, the entire process of scientific publication becomes more trustworthy and less susceptible to outside influence. Scientific arbitration boards can help adjudicate major conflicts while protecting the integrity of the publisher and journal editors. Editorial independence within the physical constraints of the journal promotes a free and open exchange of ideas unhampered by the economics of running a medical publication. Combined with transparency and a legal framework to protect publishers and editors, undue influence by advertisers and competing interests can be minimized. There have been a number of challenges to scientific integrity in recent years. Without aggressive intervention by editors and publishers, the public's confidence in scientific scholarship will falter. This may lead to a shift in priorities in funding for medical research, impede research endeavors, and delay timely care that we provide to our patients. Further, if there is not a thoughtful and effective framework in place for publishers to deal with these issues, we may find ourselves policed by external entities that do not appreciate all of the finer points of medical research.