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Conflicts of Interest and Disclosures in Publications
Journal Policy
Conflicts of Interest and Disclosures in Publications MICHAEL CAMILLERI*, ERIN C. DUBNANSKY‡, and ANIL K. RUSTGI§ *Editors of Clinical Gastroenterology and Hepatology and §Gastroenterology and ‡Director of Editorial Services, AGA Institute
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he general objectives of this combined commentary from the Editors of Gastroenterology and Clinical Gastroenterology and Hepatology (CGH) are to address the increasing concerns regarding appropriate disclosures as they relate to actual or potential conflicts of interest in articles published in the journals. What are the overarching principles governing such disclosures? What are the overt conflicts encountered? What are unappreciated conflicts that require disclosure? Is full disclosure alone sufficient in the management of conflict of interest? What is needed to enhance this process and not discourage authors from submitting their manuscripts for consideration?
What Is the Problem? There is a public perception that the medical profession is tainted by personal financial gain, and that editors face accusations of leniency.1 This perception is fostered by statements in the popular press that gifting itself, rather than the amount given creates a sense of loyalty and indebtedness, and that the medical profession is potentially influenced in its appraisal of clinical medicine, clinical trials, and biomedical research. In some situations, such as at the Food and Drug Administration (FDA) advisory committee meetings, medical experts consulting with the corporate world result in their recusal. Ultimately, those most capable of providing feedback might be recused, and this strategy might not best serve the public interest. Authoritative policy statements, such as those of the Association of American Medical Colleges (AAMC) or the Association of American Universities, have provided guidance regarding the management of individual and, to a lesser extent, institutional conflicts of interest. Academic groups continue to address the major financial conflicts pertaining to the profession with several recommendations.2,3 Dr Jordan Cohen, past president of the AAMC, commented “The working group’s recommendations are uncommonly demanding and reflect the urgency of reversing present practices.” The 7 main recommendations were the following3: 1. Ban all gifts (large and small) from drug and device makers, including free meals.
2. Prohibit direct support of continuing medical education programs (including travel) by industry. 3. Establish a central fund, thereby pooling unrestricted gifts from multiple sources in a fund to be administered and distributed by the academic medical center. 4. Prohibit direct provision of drug samples to physicians; create an “arms-length” system for providing such samples to indigent patients. 5. Prohibit direct financial relationships with drug or device companies for formulary committee members. 6. Prohibit participation in speakers’ bureaus that are regarded as part of the marketing system for industry. 7. Prohibit publishing anything “ghostwritten” by industry employees. By contrast, disclosures in publications have not been specifically addressed in sufficient detail in these policy statements, and there are no federally mandated management guidelines. Yet, the popular press has developed a significant interest in the challenges presented to journal editors. For example, the following is an excerpt from the New York Times, August 1, 20061: “Sharks are circling Dr. DeAngelis because she advocates forcing authors of journal articles to disclose every penny they take that may create a conflict of interest. But now the authors of several JAMA articles have failed to make the disclosures, and Dr. DeAngelis has been accused of carelessness.” The International Committee of Medical Journal Editors (ICMJE) provides guidance on disclosures in publications with a policy (Appendix [see supplemental material online at www.gastrojournal.org])4 that has been adopted by many biomedical journals, including Gastroenterology and CGH. However, some of the recommendations of the ICMJE policy have not been unequivocally enforced in the AGA Institute journals’ disclosure proAbbreviations used in this paper: AAMC, American Association of Medical Colleges; AGA, American Gastroenterological Association; CGH, Clinical Gastroenterology and Hepatology; FDA, Food and Drug Administration; ICMJE, International Committee of Medical Journal Editors; JAMA, Journal of the American Medical Association; NEJM, New England Journal of Medicine. © 2007 by the AGA Institute 0016-5085/07/$32.00 doi:10.1053/j.gastro.2007.01.052 GASTROENTEROLOGY 2007;132:841– 847
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Table 1. Disclosure Policy for the AGA Institute Journals I. Authors (Original Articles and Review articles) The following information must be included on the title page of submitted manuscripts: 䡩 A list for all authors that discloses any financial arrangement (eg, consultancies, stock ownership, equity interests, patent licensing arrangements, research support, major honoraria, etc) they might have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Interactions that occur from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is longer, are pertinent. In the absence of any conflict of interest, authors must make the statement that there is no conflict to disclose. 䡩 A statement of all funding sources supporting the work and all institutional or corporate affiliations. 䡩 Individuals who provided writing assistance for the manuscript and the funding source for this assistance must be disclosed. 䡩 Investigators must disclose potential conflicts to study participants and must state whether they have done so. 䡩 All phase II or III trials pertaining to a commercial product (pharmaceutical or device) require: a. A statement that the statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician who is not employed by the corporate entity (the name of the biostatistician must be provided); and b. A statement from the corresponding author that he or she had full access to all of the data and takes full responsibility for the veracity of the data and analysis. All authors for each manuscript will also need to continue to complete and submit to the journals’ editorial office the Authorship Responsibility portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/ Animal Care Committee Approval, and Sponsorship form on submission of a manuscript. 䡩 Authors must describe the role of the study sponsor(s), if any, in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. II. Reviewers and Editorialists 䡩 Reviewers and editorialists will be disqualified from reviewing or from writing an editorial if they: a. have had an ongoing collaboration, original publications, or grants with the authors within the previous 2 years, except in the case of being a part of a multicenter group from a different site; or b. are from the same institution as the authors. 䡩 Reviewers and editorialists should disclose at the time of submission of their review or editorial any financial arrangement (eg, consultancies, stock ownership, equity interests, patent licensing arrangements, research support, major honoraria, etc) they might have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Interactions that occur from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is longer, are pertinent.
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cess; changes to ensure tighter control and greater oversight are provided in this commentary (the AGA Institute Ethics Committee and Governing Board approved these changes in November 2006). The full AGA Institute policy on disclosure in publications is included in Table 1. Authors and academics seem to be getting mixed messages. The Bayh-Dole law of 1980 has empowered investigators and academic institutions to commercialize intellectual property and inventions. Leading journal editors have provided and updated guidance during the last decade5–10 that contributed to the formulation of the ICMJE guidelines. However, there has been variable attention to ensure that financial interests are disclosed or investigators recuse themselves from some of the research as part of the management strategies for such conflicts of interest.
What Are Downsides of Full Disclosure? There is also a potential downside to mandating full disclosures in articles. What is a reader to believe in an article that includes full disclosure? What disclosures are relevant to the content of the article? What relationships are more likely, if at all, to influence the author’s judgment? Does the reader perceive the disclosures as potentially influencing the author? Are disclosures of industry relationships that are governed by an auditable research contract or an exchange transaction with expectations and deliverables regarded as equally conflicting as those that result in personal financial gain? There are also potential risks when making the task so onerous that full disclosure is not provided, and the one important and relevant conflict might be omitted. In the instructions to authors for the New England Journal of Medicine (NEJM), one reads: “The statement should describe the authors’ relationships with companies that make products relevant to the paper. The statement should specify the type of relationships (e.g., consulting, paid speaking, grant support, equity, patents) each author has with each company. The information should be consistent with the authors’ signed financial disclosure forms.”
What Are Some of the Editor’s Concerns? As Editors, the lack of clarity and uniformity in the recommendations on disclosure results in several challenges. First, there is potentially insufficient appreciation among some authors of the imperative to disclose conflicts of interest. Second, as Editors, we attempt carefully to avoid inadvertently facilitating the marketing strategies of the industry sponsors as conflicted authors present a potentially controversial interpretation of the data. Third, the Editors are trying continually to achieve balance, upholding the journal’s standards for scientific
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Table 2. Principles of Disclosures in the New England Journal of Medicine ● Authors of Original Articles, Special Articles, Sounding Board articles, Case Records, and Perspectives require disclosure of the 䡩 sponsorship of the studies and relevant financial information about the authors; and 䡩 financial relationships with biomedical companies, such as consulting fees, service on advisory boards, ownership of equity (or options thereon), patent royalties, honorariums for lectures, fees for expert testimony, and research grants. ● Authors of Review articles and Editorials, which summarize published articles and synthesize conclusions but do not present new data, will not have any significant financial interest in a company (or its competitor) that makes a product discussed in the article. ● Significant financial associations are specified, and interactions that occur within 2 years before the publication date of an article are deemed pertinent for the decision whether an individual has to be recused from authorship. 䡩 Upper limit on the annual sum that a person might receive before a relationship is automatically considered significant (the limit, currently $10,000) is referred to as the de minimis level. 䡩 Significant interest is any holding in which the potential for profits is not limited, such as stock, stock options, and patent positions. Policy includes both publicly and privately traded companies. 䡩 With respect to research grants, authors are required not to have major research support or a major proportion of their funding from relevant companies.
rigor while knowing that an important revenue source for the journal comes from advertising or selling of reprints of clinical trials. So lucrative is this business that some journals actually solicit phase IIB or III trial articles with a special “fast track” process. The AGA Institute journals have not followed that approach. It might be the ultimate representation of financial conflict of interest of the journal and the sponsoring society if the journal knowingly facilitates the publication of articles that are likely to provide a generous revenue stream from the sale of reprints or advertising space in the journal. It has been suggested that the disclosure that the Massachusetts Medical Society (owner of the NEJM) recorded profits in excess of $80 million in a recent year is itself worthy of further investigation.11 Do we as editors, and the AGA Institute through its journals, actually have conflicts of interest in selecting such articles that ensure a profit for the journal?
What Are the Principles That Govern Disclosure? There have been many attempts by influential journals to encourage disclosure of conflicts of interest by authors. It is generally appreciated that reporting the financial conflicts of interest of authors and of the relationships between investigators and funding sources is essential to help maintain confidence and trust in the scientific integrity of medical research articles.
The principles followed by the NEJM (Table 2) and the Journal of the American Medical Association (JAMA) (Table 3) provide some of the best guidance available. As Editors, we appreciate the perils of not following these principles. This is illustrated by the case of the November 2000 NEJM article, “Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients With Rheumatoid Arthritis,” which resulted in a “ping-pong” match of claims, concerns, counterclaims, and reaffirmed concerns.11–15 The NEJM’s expression of concern was prompted by evidence that the article did not accurately represent the safety data available to the authors when the article was being reviewed for publication. Without wishing to adjudicate on the specific controversy, it is conceivable that it might have been avoided by requiring independent statistical analysis of industry-funded multicenter studies whenever employees of the sponsor are co-authors, particularly when the statement of participation shows that the company employees were primarily responsible for the statistical analysis. This is a requirement for manuscripts reporting industry-sponsored studies that are submitted to the JAMA. Table 3. Principles of Author Disclosure in the Journal of American Medical Association A. All authors of all manuscripts submitted to the JAMA (including research reports, reviews, opinion pieces, letters to the editor, and book reviews) must ● Report complete disclosures and if applicable, declaration of no conflicts 䡩 Within the past 5 years and foreseeable future (eg, employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, royalties) 䡩 With any organization or entity with a financial interest in or with any organization or entity with financial conflict with the subject matter or materials discussed in the manuscript ● Report detailed information regarding all financial and material support for the research and work. This includes, but is not limited to, all grant support and funding sources, any provision of equipment and supplies, and other paid contributions ● Report in “Acknowledgment” section, statement to include 䡩 The work of paid or employed writers, statisticians, epidemiologists, and others involved with data management and analyses 䡩 Declaration of no conflicts of interest when applicable ● Complete and sign an authorship responsibility form that includes statements on conflict of interest as well as funding and support B. In reporting industry-sponsored studies ● The authors must attest “I had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis” ● If the data analysis has been conducted only by statisticians employed by the company sponsoring the research, the study will not be accepted unless there is additional independent analysis of the data conducted by statisticians at a medical school, academic medical center, or government research institute. The entire raw data set must be given to an independent biostatistician, along with study protocol and pre-specified plan for data analysis. 843
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What Are Current Problems in the Management of Conflicts Through Disclosure? One of the key challenges of managing potential conflicts of interest relates to the misperception of what constitutes a conflict, in part because of the lack of formal education during training or continued education after graduation. This situation contrasts with the certification required for participation in human or animal research. Some also perceive a lack of no proportionality in levels of conflict, eg, the de minimis for significant financial conflict of interest is $10,001, which was set in federal guidelines in 1996, and some would argue that the level of conflict is different when an individual receives $10,002 associated with real work conducted during a period of a year versus $100,000 per year in fees that are not justified by the work performed and appear more likely to be associated with “loyalty” of the recipient. Meanwhile, there are other potentially conflicting relationships that do not appear to attract as much attention, such as owning an education company and receiving unrestricted grants from a company while participating in the authorship of original research or systematic reviews/meta-analyses. By contrast, authors might be deemed conflicted when they receive auditable research grants with no associated personal gain and with identified deliverables in the form of a purely academic output. Should such relationships be brushed with the same patina?
“Legalese” and Challenges in Comprehension or Implementation of the International Committee of Medical Journal Editors’ Guidelines The following are some examples in which the guidelines or their application are unclear.
Disclosure Relevant to the Subject of the Manuscript One of the Editors recently encountered a situation in which a manuscript addressed the adverse effects of 2 of 3 drugs in a class but excluded the third approved drug with the same pharmacologic action on the grounds that it was a different chemical class. It turned out that the authors had received grants from makers of the third drug, which was included in the discussion of the manuscript but was excluded from the analysis of the adverse effects. The disclosure policy for authors of the AGA Institute journals follows more closely the NEJM than the JAMA policy. However, there is an additional ambiguity introduced because the AGA Institute journals determine that disclosure is necessary when the “product figures prominently in the submitted manuscript.” Prominence and relevance are relative terms that are prone to 844
subjective interpretation. Applying this criterion, it might have been justifiable for the authors in the above case to restrict their discussion to the 2 drugs while “protecting” the third drug with which they were potentially conflicted.
Detailed Information Should Include, But Is Not Limited to, All Grant Support and Funding Sources, Any Provision of Equipment and Supplies, and Other Paid Contributions Readers (and Editors) might not completely understand “other paid contributions.” Is there a de minimis that requires disclosure? Should this disclosure be guided by the federal guidelines on the definition of significant financial conflict of interest (⬎$10,000 per year from an individual sponsor)?
Term of Reference for Disclosures “Past five years and foreseeable future” is the term of reference for disclosures used at the JAMA. “Past two years and anticipated in the next year” are used at the NEJM. Apart from the ambiguity in the word foreseeable, the differences or lack of consistency among journals create confusion.
Conflicts Arising From Equity in Publicly Traded Companies The NEJM determines that equity in publicly traded or in privately held companies requires disclosure, but the de minimis for the equity owned in a publicly traded company is not specified in the 1996 and 2002 statements from the NEJM. Other journals do not specifically address this distinction. Journals generally place the de minimis at the federal threshold for significant conflict of interest, which is $10,000. One might question whether stock or equity held in a publicly traded company worth $10,001 and held over 5 years is as conflicting as receiving consulting fees of $10,001 per year for 5 years. All journals characterize stock options as significant conflicts.
Relationships With Entities With a Financial Interest in or Financial Conflict With the Subject Matter or Materials Discussed in the Manuscript If followed strictly to its logical conclusion, this requirement for disclosure extends to all competing companies pertinent to the subject matter. This provides a significant burden in the disclosure process and likely results in difficulty with compliance with the requisite disclosure. The net result of all the variations in disclosure policies is a significant degree of confusion among authors. The editors of the JAMA10 recently noted: “Biomedical jour-
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nals have a wide range of conflict of interest policies (e.g. some request disclosures, some require disclosures, and some publish disclosures and some do not). Journals also define relevant conflicts of interest in different terms to include financial and non-financial conflicts or only financial interests, and for financial interests, may define relevance in different monetary amounts or lengths of time.” It is possible that these different policies lead some authors to not understand fully or to misunderstand what is expected and provide inaccurate or incomplete disclosures. Thus, significant conflicts of interest might only be discovered after publication and necessitate publication of corrections or letters of explanation. Perhaps it is time to have uniform guidelines for authors among all journals.
What Is New in the Conflict of Interest Sphere? Will New Approaches Resolve the Challenges? There are novel, possibly underappreciated conflicts and changes that arise with the introduction of new technology. For example, there has been a veritable mushrooming of education companies owned by individuals or academic medical centers. Some view these as a means to “launder” the activities previously conducted by the speakers’ bureaus of the companies that have been regarded as marketing tools for the companies.3 These education companies receive unrestricted grants from companies. The content of education might or might not be product-related; Council on Medical Education credits usually are provided. Several questions arise. Should owners of such companies be allowed to author papers about the products of their sponsors? When non-owners who receive personal compensation serve as authors, should they disclose these as relationships with the industry sponsor of the educational activity, or is the relationship one step removed and therefore “sanitized” by the inclusion of the professional education company? The introduction of new technology will bring new challenges in the management of conflict of interest in publications. Physicians in the procedure specialties like gastroenterology are invited to participate at companyowned education institutes. There has been explosive growth in the opportunities to train future clinicians in new technology by using simulation and procedure labs. There is a very real need for this form of technologic education because national societies and boards do not own these simulators. The best academics, proceduralists, and role models are required for this education and credentialing. How should that industry relationship be disclosed? Should society expect that experts provide such education for no personal remuneration or compensation to their department for their time away from
their practices? If no remuneration is received personally, then is this relationship conflicting when it is done as a service to the specialty and ultimately to society?
Conflicts in Publications Arising From Corporate-Funded Research The general tenet that personal gain should never come in the way of participant safety is sacrosanct. Institutional review boards are charged with ensuring and monitoring human subject safety. However, there are no definite or universally applied guidelines on the level of personal equity that should result in recusal. Some academic centers use the same threshold recommended in federal guidelines. For many academics, corporatefunded research will not be associated with any personal financial gain. Is there a significant conflict of interest when there is a transparent, auditable research budget with justifiable compensation for supplies, patient care costs, and salary support for the research team and a contract negotiated by the academic medical center rather than the individual? Clearly, this research support needs to be disclosed in the publication, but it would appear important to separate this form of conflict from that associated with personal gain. At the same time, it would also appear important to ensure that the authors do not serve for personal gain as consultants to the company for at least the duration of the research study and the time until the manuscript is published. Journals differ on the need to disclose research funding and any personal relationship with the sponsor in the consent form. In accordance with the ICMJE guidelines, some editors retain the right to review the protocol and the consent form. A final question arises: Should investigators conducting research on a corporate-funded project participate in education/consulting with personal payment from an education company that received an “unrestricted” education grant from the same corporate sponsor?
Is Disclosure Sufficient? Does Recusal Work? Clearly, there are situations in which disclosure is insufficient and recusal would be the preferred management strategy. The AAMC guidelines address exceptional circumstances under the provisions of the “rebuttable presumption” of conflict. The NEJM approach is to provide a proactive review and determine whether the article should be allowed to be submitted. This approach seems to work except when the author does not disclose accurately. Recusal results in a loss of expertise required by the field and the journal readers when the range of conflict is broad, and there are no federal or AAMC guidelines on different forms and degrees of conflict, eg, personal in845
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come versus research grants with completely auditable budget and independently corroborated data/statistical analysis. The NEJM acknowledged in an editorial that its policy for editorialists (any financial conflict of interest) was too stringent, and it modified the policy to include “significant” in 2002.7 Recusal is sometimes appropriate in the conduct of research and authorship of journal articles, but it carries with it a cost to the readers, journal, and ultimately, to society. The situation is somewhat analogous to participation in FDA advisory committees. The FDA recently announced several steps to help make its advisory committee processes more effective at providing timely, top tier, independent scientific advice to the agency and at reassuring the public about the basic integrity of this process.16 As editors, we seek to separate situations that require recusal from those that can be best managed with appropriate disclosure, so that the reader can be informed but not dissuaded from reading or believing the content of an article.
Changes to Disclosure Policy of the AGA Institute Journals Current understanding and commitment to disclosure among authors are suboptimal. Given the variation in the journal policies on disclosure and their implementation, there is a need for consensus through a joint statement by representative academic bodies and their journals; consensus should be reached to provide uniform definition, review, and management strategies that would be common for all journals. Thus, authors would not have to revise disclosures when manuscripts move from one journal to another. In an effort to adhere more closely with the ICMJE guidelines, the AGA Institute journals have revised their disclosure policy; specific changes are listed below and took effect in January 2007: 1. Authors are reminded to include pertinent information when submitting manuscripts via the journals manuscript submission system, Editorial Manager. In some cases, if the required information is not included with the submission, manuscripts are returned to the authors and are not entered into the peer review process until all required information is provided. 2. The title page of all submitted manuscripts must include all author conflict of interest disclosures or, in the absence of any conflict of interest, make the statement that there is no conflict to disclose. All authors for each manuscript must also continue to complete and submit to the journals’ editorial office the Financial Disclosure portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship form upon submission of a manuscript. 846
3. Authors must identify on the title page individuals who provided writing assistance and disclose the funding source for this assistance. 4. Investigators must disclose potential conflicts to study participants and must state on the manuscript title page whether they have done so. 5. All phase II or III trials pertaining to a commercial product (pharmaceutical or device) will require: a. A statement included on the title page that the statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) has been independently confirmed by a biostatistician who is not employed by the corporate entity (the name of the biostatistician must be provided); and b. A statement on the title page from the corresponding author that he or she had full access to all of the data and takes full responsibility for the veracity of the data and analysis. All authors for each manuscript will also need to continue to complete and submit to the journals’ editorial office the Authorship Responsibility portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship form on submission of a manuscript. 6. Authors must describe on the title page the role of the study sponsor(s), if any, in the study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. 7. The Editors shall have the right to review the study protocol and entire dataset for corroboration of the study results. 8. The period defining the potential conflict of interest would be from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is the longer. 9. Reviewers, Editors, and editorial staff must not use knowledge of the work before its publication to further their own interests. Although this has been based on an honor system in the past, proof that this has occurred might result in placing the reviewer, Editor, or editorial staff member on probation as a contributor to the journals of the AGA Institute. As Editors, we agree that it is essential for the medical profession to take the whole charge on conflict of interest seriously. What is at stake are not only our credibility and respect but also our autonomy to self-regulate before society demands stricter enforcement or policies that might not be based on the best interests of patients or medical science.
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Appendix Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1053/ j.gastro.2007.01.052. References 1. McNeil DG. Tough-talking editor faces accusation of leniency. The New York Times, August 1, 2006. Available at: http://www. nytimes.com/2006/08/01/science/01prof.html. Accessed August 5, 2006. 2. Cohen JJ. A word from the president: let’s look a gift horse in the mouth. Reporter. Vol 10. Available at: http://www.aamc.org/ newsroom/reporter/june01/word.htm. Accessed August 25, 2006. 3. Brennan TA, Rothman DJ, Blank L, et al. Health industry practices that create conflicts of interest: a policy proposal for academic medical centers. JAMA 2006;25;295:429 – 433. 4. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication. 2005. Section II D. Conflicts of Interest. Available at: http://www.icmje.org. Accessed January 25, 2007. 5. Angell M, Kassirer JP. Editorials and conflicts of interest. N Engl J Med 1996;335:1055–1056. 6. Davidoff F, DeAngelis CD, Drazen JM, et al. Sponsorship, authorship, and accountability. JAMA 2001;286:1232–1234. 7. Drazen JM, Curfman GD. Financial associations of authors. N Engl J Med 2002;346:1901–1902. 8. DeAngelis CD, Fontanarosa PB, Flanagin A. Reporting financial conflicts of interest and relationships between investigators and research sponsors. JAMA 2001;286:89 –91.
9. Instructions for authors. JAMA 2005;294:119 –125. 10. Flanagin A, Fontanarosa PB, DeAngelis CD. Update on JAMA’s conflict of interest policy. JAMA 2006;296:220 –221. 11. Armstrong, David. “Bitter pill: how the New England Journal missed warning signs on Vioxx: medical weekly waited years to report flaws in article that praised pain drug—Merck seen as ‘punching bag’.” Wall Street Journal May 15, 2006:A1. Accessed Aug 25, 2006, through Proquest database. 12. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR study group. N Engl J Med 2000;343:1520 –1528, 2 p following 1528. 13. Curfman GD, Morrissey S, Drazen JM. Expression of concern: Bombardier et al, “comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.” N Engl J Med 2005;353:2813–2814. 14. Bombardier C, Laine L, Burgos-Vargas R, et al. Response to expression of concern regarding VIGOR study. N Engl J Med 2006;354:1196 –1199. 15. Curfman GD, Morrissey S, Drazen JM. Expression of concern reaffirmed. N Engl J Med. 2006;354:1193. 16. FDA announces plan to strengthen advisory committee processes. FDA News, July 24, 2006. Available at: http://www. fda.gov/bbs/topics/NEWS/2006/NEW01416.html. Accessed August 25, 2006.
Address requests for reprints to: Michael Camilleri, MD, Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, Minnesota 55905; e-mail: [email protected]; fax: (507) 255-5720. The authors wish to thank the associate editors of Clinical Gastroenterology and Hepatology and Gastroenterology for their valuable input to this commentary.
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Conflicts of Interest and Disclosures in Publications MICHAEL CAMILLERI*, ERIN C. DUBNANSKY‡, and ANIL K. RUSTGI§ *Editors of Clinical Gastroenterology and Hepatology and §Gastroenterology and ‡Director of Editorial Services, AGA Institute
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he general objectives of this combined commentary from the Editors of Gastroenterology and Clinical Gastroenterology and Hepatology (CGH) are to address the increasing concerns regarding appropriate disclosures as they relate to actual or potential conflicts of interest in articles published in the journals. What are the overarching principles governing such disclosures? What are the overt conflicts encountered? What are unappreciated conflicts that require disclosure? Is full disclosure alone sufficient in the management of conflict of interest? What is needed to enhance this process and not discourage authors from submitting their manuscripts for consideration?
What Is the Problem? There is a public perception that the medical profession is tainted by personal financial gain, and that editors face accusations of leniency.1 This perception is fostered by statements in the popular press that gifting itself, rather than the amount given creates a sense of loyalty and indebtedness, and that the medical profession is potentially influenced in its appraisal of clinical medicine, clinical trials, and biomedical research. In some situations, such as at the Food and Drug Administration (FDA) advisory committee meetings, medical experts consulting with the corporate world result in their recusal. Ultimately, those most capable of providing feedback might be recused, and this strategy might not best serve the public interest. Authoritative policy statements, such as those of the Association of American Medical Colleges (AAMC) or the Association of American Universities, have provided guidance regarding the management of individual and, to a lesser extent, institutional conflicts of interest. Academic groups continue to address the major financial conflicts pertaining to the profession with several recommendations.2,3 Dr Jordan Cohen, past president of the AAMC, commented “The working group’s recommendations are uncommonly demanding and reflect the urgency of reversing present practices.” The 7 main recommendations were the following3: 1. Ban all gifts (large and small) from drug and device makers, including free meals.
2. Prohibit direct support of continuing medical education programs (including travel) by industry. 3. Establish a central fund, thereby pooling unrestricted gifts from multiple sources in a fund to be administered and distributed by the academic medical center. 4. Prohibit direct provision of drug samples to physicians; create an “arms-length” system for providing such samples to indigent patients. 5. Prohibit direct financial relationships with drug or device companies for formulary committee members. 6. Prohibit participation in speakers’ bureaus that are regarded as part of the marketing system for industry. 7. Prohibit publishing anything “ghostwritten” by industry employees. By contrast, disclosures in publications have not been specifically addressed in sufficient detail in these policy statements, and there are no federally mandated management guidelines. Yet, the popular press has developed a significant interest in the challenges presented to journal editors. For example, the following is an excerpt from the New York Times, August 1, 20061: “Sharks are circling Dr. DeAngelis because she advocates forcing authors of journal articles to disclose every penny they take that may create a conflict of interest. But now the authors of several JAMA articles have failed to make the disclosures, and Dr. DeAngelis has been accused of carelessness.” The International Committee of Medical Journal Editors (ICMJE) provides guidance on disclosures in publications with a policy (Appendix [see supplemental material online at www.gastrojournal.org])4 that has been adopted by many biomedical journals, including Gastroenterology and CGH. However, some of the recommendations of the ICMJE policy have not been unequivocally enforced in the AGA Institute journals’ disclosure proAbbreviations used in this paper: AAMC, American Association of Medical Colleges; AGA, American Gastroenterological Association; CGH, Clinical Gastroenterology and Hepatology; FDA, Food and Drug Administration; ICMJE, International Committee of Medical Journal Editors; JAMA, Journal of the American Medical Association; NEJM, New England Journal of Medicine. © 2007 by the AGA Institute 0016-5085/07/$32.00 doi:10.1053/j.gastro.2007.01.052 GASTROENTEROLOGY 2007;132:841– 847
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Table 1. Disclosure Policy for the AGA Institute Journals I. Authors (Original Articles and Review articles) The following information must be included on the title page of submitted manuscripts: 䡩 A list for all authors that discloses any financial arrangement (eg, consultancies, stock ownership, equity interests, patent licensing arrangements, research support, major honoraria, etc) they might have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Interactions that occur from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is longer, are pertinent. In the absence of any conflict of interest, authors must make the statement that there is no conflict to disclose. 䡩 A statement of all funding sources supporting the work and all institutional or corporate affiliations. 䡩 Individuals who provided writing assistance for the manuscript and the funding source for this assistance must be disclosed. 䡩 Investigators must disclose potential conflicts to study participants and must state whether they have done so. 䡩 All phase II or III trials pertaining to a commercial product (pharmaceutical or device) require: a. A statement that the statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) have been independently confirmed by a biostatistician who is not employed by the corporate entity (the name of the biostatistician must be provided); and b. A statement from the corresponding author that he or she had full access to all of the data and takes full responsibility for the veracity of the data and analysis. All authors for each manuscript will also need to continue to complete and submit to the journals’ editorial office the Authorship Responsibility portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/ Animal Care Committee Approval, and Sponsorship form on submission of a manuscript. 䡩 Authors must describe the role of the study sponsor(s), if any, in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. II. Reviewers and Editorialists 䡩 Reviewers and editorialists will be disqualified from reviewing or from writing an editorial if they: a. have had an ongoing collaboration, original publications, or grants with the authors within the previous 2 years, except in the case of being a part of a multicenter group from a different site; or b. are from the same institution as the authors. 䡩 Reviewers and editorialists should disclose at the time of submission of their review or editorial any financial arrangement (eg, consultancies, stock ownership, equity interests, patent licensing arrangements, research support, major honoraria, etc) they might have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Interactions that occur from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is longer, are pertinent.
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cess; changes to ensure tighter control and greater oversight are provided in this commentary (the AGA Institute Ethics Committee and Governing Board approved these changes in November 2006). The full AGA Institute policy on disclosure in publications is included in Table 1. Authors and academics seem to be getting mixed messages. The Bayh-Dole law of 1980 has empowered investigators and academic institutions to commercialize intellectual property and inventions. Leading journal editors have provided and updated guidance during the last decade5–10 that contributed to the formulation of the ICMJE guidelines. However, there has been variable attention to ensure that financial interests are disclosed or investigators recuse themselves from some of the research as part of the management strategies for such conflicts of interest.
What Are Downsides of Full Disclosure? There is also a potential downside to mandating full disclosures in articles. What is a reader to believe in an article that includes full disclosure? What disclosures are relevant to the content of the article? What relationships are more likely, if at all, to influence the author’s judgment? Does the reader perceive the disclosures as potentially influencing the author? Are disclosures of industry relationships that are governed by an auditable research contract or an exchange transaction with expectations and deliverables regarded as equally conflicting as those that result in personal financial gain? There are also potential risks when making the task so onerous that full disclosure is not provided, and the one important and relevant conflict might be omitted. In the instructions to authors for the New England Journal of Medicine (NEJM), one reads: “The statement should describe the authors’ relationships with companies that make products relevant to the paper. The statement should specify the type of relationships (e.g., consulting, paid speaking, grant support, equity, patents) each author has with each company. The information should be consistent with the authors’ signed financial disclosure forms.”
What Are Some of the Editor’s Concerns? As Editors, the lack of clarity and uniformity in the recommendations on disclosure results in several challenges. First, there is potentially insufficient appreciation among some authors of the imperative to disclose conflicts of interest. Second, as Editors, we attempt carefully to avoid inadvertently facilitating the marketing strategies of the industry sponsors as conflicted authors present a potentially controversial interpretation of the data. Third, the Editors are trying continually to achieve balance, upholding the journal’s standards for scientific
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Table 2. Principles of Disclosures in the New England Journal of Medicine ● Authors of Original Articles, Special Articles, Sounding Board articles, Case Records, and Perspectives require disclosure of the 䡩 sponsorship of the studies and relevant financial information about the authors; and 䡩 financial relationships with biomedical companies, such as consulting fees, service on advisory boards, ownership of equity (or options thereon), patent royalties, honorariums for lectures, fees for expert testimony, and research grants. ● Authors of Review articles and Editorials, which summarize published articles and synthesize conclusions but do not present new data, will not have any significant financial interest in a company (or its competitor) that makes a product discussed in the article. ● Significant financial associations are specified, and interactions that occur within 2 years before the publication date of an article are deemed pertinent for the decision whether an individual has to be recused from authorship. 䡩 Upper limit on the annual sum that a person might receive before a relationship is automatically considered significant (the limit, currently $10,000) is referred to as the de minimis level. 䡩 Significant interest is any holding in which the potential for profits is not limited, such as stock, stock options, and patent positions. Policy includes both publicly and privately traded companies. 䡩 With respect to research grants, authors are required not to have major research support or a major proportion of their funding from relevant companies.
rigor while knowing that an important revenue source for the journal comes from advertising or selling of reprints of clinical trials. So lucrative is this business that some journals actually solicit phase IIB or III trial articles with a special “fast track” process. The AGA Institute journals have not followed that approach. It might be the ultimate representation of financial conflict of interest of the journal and the sponsoring society if the journal knowingly facilitates the publication of articles that are likely to provide a generous revenue stream from the sale of reprints or advertising space in the journal. It has been suggested that the disclosure that the Massachusetts Medical Society (owner of the NEJM) recorded profits in excess of $80 million in a recent year is itself worthy of further investigation.11 Do we as editors, and the AGA Institute through its journals, actually have conflicts of interest in selecting such articles that ensure a profit for the journal?
What Are the Principles That Govern Disclosure? There have been many attempts by influential journals to encourage disclosure of conflicts of interest by authors. It is generally appreciated that reporting the financial conflicts of interest of authors and of the relationships between investigators and funding sources is essential to help maintain confidence and trust in the scientific integrity of medical research articles.
The principles followed by the NEJM (Table 2) and the Journal of the American Medical Association (JAMA) (Table 3) provide some of the best guidance available. As Editors, we appreciate the perils of not following these principles. This is illustrated by the case of the November 2000 NEJM article, “Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients With Rheumatoid Arthritis,” which resulted in a “ping-pong” match of claims, concerns, counterclaims, and reaffirmed concerns.11–15 The NEJM’s expression of concern was prompted by evidence that the article did not accurately represent the safety data available to the authors when the article was being reviewed for publication. Without wishing to adjudicate on the specific controversy, it is conceivable that it might have been avoided by requiring independent statistical analysis of industry-funded multicenter studies whenever employees of the sponsor are co-authors, particularly when the statement of participation shows that the company employees were primarily responsible for the statistical analysis. This is a requirement for manuscripts reporting industry-sponsored studies that are submitted to the JAMA. Table 3. Principles of Author Disclosure in the Journal of American Medical Association A. All authors of all manuscripts submitted to the JAMA (including research reports, reviews, opinion pieces, letters to the editor, and book reviews) must ● Report complete disclosures and if applicable, declaration of no conflicts 䡩 Within the past 5 years and foreseeable future (eg, employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, royalties) 䡩 With any organization or entity with a financial interest in or with any organization or entity with financial conflict with the subject matter or materials discussed in the manuscript ● Report detailed information regarding all financial and material support for the research and work. This includes, but is not limited to, all grant support and funding sources, any provision of equipment and supplies, and other paid contributions ● Report in “Acknowledgment” section, statement to include 䡩 The work of paid or employed writers, statisticians, epidemiologists, and others involved with data management and analyses 䡩 Declaration of no conflicts of interest when applicable ● Complete and sign an authorship responsibility form that includes statements on conflict of interest as well as funding and support B. In reporting industry-sponsored studies ● The authors must attest “I had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis” ● If the data analysis has been conducted only by statisticians employed by the company sponsoring the research, the study will not be accepted unless there is additional independent analysis of the data conducted by statisticians at a medical school, academic medical center, or government research institute. The entire raw data set must be given to an independent biostatistician, along with study protocol and pre-specified plan for data analysis. 843
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What Are Current Problems in the Management of Conflicts Through Disclosure? One of the key challenges of managing potential conflicts of interest relates to the misperception of what constitutes a conflict, in part because of the lack of formal education during training or continued education after graduation. This situation contrasts with the certification required for participation in human or animal research. Some also perceive a lack of no proportionality in levels of conflict, eg, the de minimis for significant financial conflict of interest is $10,001, which was set in federal guidelines in 1996, and some would argue that the level of conflict is different when an individual receives $10,002 associated with real work conducted during a period of a year versus $100,000 per year in fees that are not justified by the work performed and appear more likely to be associated with “loyalty” of the recipient. Meanwhile, there are other potentially conflicting relationships that do not appear to attract as much attention, such as owning an education company and receiving unrestricted grants from a company while participating in the authorship of original research or systematic reviews/meta-analyses. By contrast, authors might be deemed conflicted when they receive auditable research grants with no associated personal gain and with identified deliverables in the form of a purely academic output. Should such relationships be brushed with the same patina?
“Legalese” and Challenges in Comprehension or Implementation of the International Committee of Medical Journal Editors’ Guidelines The following are some examples in which the guidelines or their application are unclear.
Disclosure Relevant to the Subject of the Manuscript One of the Editors recently encountered a situation in which a manuscript addressed the adverse effects of 2 of 3 drugs in a class but excluded the third approved drug with the same pharmacologic action on the grounds that it was a different chemical class. It turned out that the authors had received grants from makers of the third drug, which was included in the discussion of the manuscript but was excluded from the analysis of the adverse effects. The disclosure policy for authors of the AGA Institute journals follows more closely the NEJM than the JAMA policy. However, there is an additional ambiguity introduced because the AGA Institute journals determine that disclosure is necessary when the “product figures prominently in the submitted manuscript.” Prominence and relevance are relative terms that are prone to 844
subjective interpretation. Applying this criterion, it might have been justifiable for the authors in the above case to restrict their discussion to the 2 drugs while “protecting” the third drug with which they were potentially conflicted.
Detailed Information Should Include, But Is Not Limited to, All Grant Support and Funding Sources, Any Provision of Equipment and Supplies, and Other Paid Contributions Readers (and Editors) might not completely understand “other paid contributions.” Is there a de minimis that requires disclosure? Should this disclosure be guided by the federal guidelines on the definition of significant financial conflict of interest (⬎$10,000 per year from an individual sponsor)?
Term of Reference for Disclosures “Past five years and foreseeable future” is the term of reference for disclosures used at the JAMA. “Past two years and anticipated in the next year” are used at the NEJM. Apart from the ambiguity in the word foreseeable, the differences or lack of consistency among journals create confusion.
Conflicts Arising From Equity in Publicly Traded Companies The NEJM determines that equity in publicly traded or in privately held companies requires disclosure, but the de minimis for the equity owned in a publicly traded company is not specified in the 1996 and 2002 statements from the NEJM. Other journals do not specifically address this distinction. Journals generally place the de minimis at the federal threshold for significant conflict of interest, which is $10,000. One might question whether stock or equity held in a publicly traded company worth $10,001 and held over 5 years is as conflicting as receiving consulting fees of $10,001 per year for 5 years. All journals characterize stock options as significant conflicts.
Relationships With Entities With a Financial Interest in or Financial Conflict With the Subject Matter or Materials Discussed in the Manuscript If followed strictly to its logical conclusion, this requirement for disclosure extends to all competing companies pertinent to the subject matter. This provides a significant burden in the disclosure process and likely results in difficulty with compliance with the requisite disclosure. The net result of all the variations in disclosure policies is a significant degree of confusion among authors. The editors of the JAMA10 recently noted: “Biomedical jour-
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nals have a wide range of conflict of interest policies (e.g. some request disclosures, some require disclosures, and some publish disclosures and some do not). Journals also define relevant conflicts of interest in different terms to include financial and non-financial conflicts or only financial interests, and for financial interests, may define relevance in different monetary amounts or lengths of time.” It is possible that these different policies lead some authors to not understand fully or to misunderstand what is expected and provide inaccurate or incomplete disclosures. Thus, significant conflicts of interest might only be discovered after publication and necessitate publication of corrections or letters of explanation. Perhaps it is time to have uniform guidelines for authors among all journals.
What Is New in the Conflict of Interest Sphere? Will New Approaches Resolve the Challenges? There are novel, possibly underappreciated conflicts and changes that arise with the introduction of new technology. For example, there has been a veritable mushrooming of education companies owned by individuals or academic medical centers. Some view these as a means to “launder” the activities previously conducted by the speakers’ bureaus of the companies that have been regarded as marketing tools for the companies.3 These education companies receive unrestricted grants from companies. The content of education might or might not be product-related; Council on Medical Education credits usually are provided. Several questions arise. Should owners of such companies be allowed to author papers about the products of their sponsors? When non-owners who receive personal compensation serve as authors, should they disclose these as relationships with the industry sponsor of the educational activity, or is the relationship one step removed and therefore “sanitized” by the inclusion of the professional education company? The introduction of new technology will bring new challenges in the management of conflict of interest in publications. Physicians in the procedure specialties like gastroenterology are invited to participate at companyowned education institutes. There has been explosive growth in the opportunities to train future clinicians in new technology by using simulation and procedure labs. There is a very real need for this form of technologic education because national societies and boards do not own these simulators. The best academics, proceduralists, and role models are required for this education and credentialing. How should that industry relationship be disclosed? Should society expect that experts provide such education for no personal remuneration or compensation to their department for their time away from
their practices? If no remuneration is received personally, then is this relationship conflicting when it is done as a service to the specialty and ultimately to society?
Conflicts in Publications Arising From Corporate-Funded Research The general tenet that personal gain should never come in the way of participant safety is sacrosanct. Institutional review boards are charged with ensuring and monitoring human subject safety. However, there are no definite or universally applied guidelines on the level of personal equity that should result in recusal. Some academic centers use the same threshold recommended in federal guidelines. For many academics, corporatefunded research will not be associated with any personal financial gain. Is there a significant conflict of interest when there is a transparent, auditable research budget with justifiable compensation for supplies, patient care costs, and salary support for the research team and a contract negotiated by the academic medical center rather than the individual? Clearly, this research support needs to be disclosed in the publication, but it would appear important to separate this form of conflict from that associated with personal gain. At the same time, it would also appear important to ensure that the authors do not serve for personal gain as consultants to the company for at least the duration of the research study and the time until the manuscript is published. Journals differ on the need to disclose research funding and any personal relationship with the sponsor in the consent form. In accordance with the ICMJE guidelines, some editors retain the right to review the protocol and the consent form. A final question arises: Should investigators conducting research on a corporate-funded project participate in education/consulting with personal payment from an education company that received an “unrestricted” education grant from the same corporate sponsor?
Is Disclosure Sufficient? Does Recusal Work? Clearly, there are situations in which disclosure is insufficient and recusal would be the preferred management strategy. The AAMC guidelines address exceptional circumstances under the provisions of the “rebuttable presumption” of conflict. The NEJM approach is to provide a proactive review and determine whether the article should be allowed to be submitted. This approach seems to work except when the author does not disclose accurately. Recusal results in a loss of expertise required by the field and the journal readers when the range of conflict is broad, and there are no federal or AAMC guidelines on different forms and degrees of conflict, eg, personal in845
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come versus research grants with completely auditable budget and independently corroborated data/statistical analysis. The NEJM acknowledged in an editorial that its policy for editorialists (any financial conflict of interest) was too stringent, and it modified the policy to include “significant” in 2002.7 Recusal is sometimes appropriate in the conduct of research and authorship of journal articles, but it carries with it a cost to the readers, journal, and ultimately, to society. The situation is somewhat analogous to participation in FDA advisory committees. The FDA recently announced several steps to help make its advisory committee processes more effective at providing timely, top tier, independent scientific advice to the agency and at reassuring the public about the basic integrity of this process.16 As editors, we seek to separate situations that require recusal from those that can be best managed with appropriate disclosure, so that the reader can be informed but not dissuaded from reading or believing the content of an article.
Changes to Disclosure Policy of the AGA Institute Journals Current understanding and commitment to disclosure among authors are suboptimal. Given the variation in the journal policies on disclosure and their implementation, there is a need for consensus through a joint statement by representative academic bodies and their journals; consensus should be reached to provide uniform definition, review, and management strategies that would be common for all journals. Thus, authors would not have to revise disclosures when manuscripts move from one journal to another. In an effort to adhere more closely with the ICMJE guidelines, the AGA Institute journals have revised their disclosure policy; specific changes are listed below and took effect in January 2007: 1. Authors are reminded to include pertinent information when submitting manuscripts via the journals manuscript submission system, Editorial Manager. In some cases, if the required information is not included with the submission, manuscripts are returned to the authors and are not entered into the peer review process until all required information is provided. 2. The title page of all submitted manuscripts must include all author conflict of interest disclosures or, in the absence of any conflict of interest, make the statement that there is no conflict to disclose. All authors for each manuscript must also continue to complete and submit to the journals’ editorial office the Financial Disclosure portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship form upon submission of a manuscript. 846
3. Authors must identify on the title page individuals who provided writing assistance and disclose the funding source for this assistance. 4. Investigators must disclose potential conflicts to study participants and must state on the manuscript title page whether they have done so. 5. All phase II or III trials pertaining to a commercial product (pharmaceutical or device) will require: a. A statement included on the title page that the statistical analysis of the entire data sets pertaining to efficacy (specifically primary and major secondary efficacy end points) and safety (specifically, serious adverse events as defined in federal guidelines) has been independently confirmed by a biostatistician who is not employed by the corporate entity (the name of the biostatistician must be provided); and b. A statement on the title page from the corresponding author that he or she had full access to all of the data and takes full responsibility for the veracity of the data and analysis. All authors for each manuscript will also need to continue to complete and submit to the journals’ editorial office the Authorship Responsibility portion of the Copyright Assignment, Authorship Responsibility, NIH Funding, Financial Disclosure, Institutional Review Board/Animal Care Committee Approval, and Sponsorship form on submission of a manuscript. 6. Authors must describe on the title page the role of the study sponsor(s), if any, in the study design in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the report for publication. 7. The Editors shall have the right to review the study protocol and entire dataset for corroboration of the study results. 8. The period defining the potential conflict of interest would be from the start of the research activity in the specific program until the time when the manuscript is anticipated to be published or 1 year from submission date, whichever is the longer. 9. Reviewers, Editors, and editorial staff must not use knowledge of the work before its publication to further their own interests. Although this has been based on an honor system in the past, proof that this has occurred might result in placing the reviewer, Editor, or editorial staff member on probation as a contributor to the journals of the AGA Institute. As Editors, we agree that it is essential for the medical profession to take the whole charge on conflict of interest seriously. What is at stake are not only our credibility and respect but also our autonomy to self-regulate before society demands stricter enforcement or policies that might not be based on the best interests of patients or medical science.
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Appendix Supplementary data Supplementary data associated with this article can be found, in the online version, at doi:10.1053/ j.gastro.2007.01.052. References 1. McNeil DG. Tough-talking editor faces accusation of leniency. The New York Times, August 1, 2006. Available at: http://www. nytimes.com/2006/08/01/science/01prof.html. Accessed August 5, 2006. 2. Cohen JJ. A word from the president: let’s look a gift horse in the mouth. Reporter. Vol 10. Available at: http://www.aamc.org/ newsroom/reporter/june01/word.htm. Accessed August 25, 2006. 3. Brennan TA, Rothman DJ, Blank L, et al. Health industry practices that create conflicts of interest: a policy proposal for academic medical centers. JAMA 2006;25;295:429 – 433. 4. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication. 2005. Section II D. Conflicts of Interest. Available at: http://www.icmje.org. Accessed January 25, 2007. 5. Angell M, Kassirer JP. Editorials and conflicts of interest. N Engl J Med 1996;335:1055–1056. 6. Davidoff F, DeAngelis CD, Drazen JM, et al. Sponsorship, authorship, and accountability. JAMA 2001;286:1232–1234. 7. Drazen JM, Curfman GD. Financial associations of authors. N Engl J Med 2002;346:1901–1902. 8. DeAngelis CD, Fontanarosa PB, Flanagin A. Reporting financial conflicts of interest and relationships between investigators and research sponsors. JAMA 2001;286:89 –91.
9. Instructions for authors. JAMA 2005;294:119 –125. 10. Flanagin A, Fontanarosa PB, DeAngelis CD. Update on JAMA’s conflict of interest policy. JAMA 2006;296:220 –221. 11. Armstrong, David. “Bitter pill: how the New England Journal missed warning signs on Vioxx: medical weekly waited years to report flaws in article that praised pain drug—Merck seen as ‘punching bag’.” Wall Street Journal May 15, 2006:A1. Accessed Aug 25, 2006, through Proquest database. 12. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR study group. N Engl J Med 2000;343:1520 –1528, 2 p following 1528. 13. Curfman GD, Morrissey S, Drazen JM. Expression of concern: Bombardier et al, “comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.” N Engl J Med 2005;353:2813–2814. 14. Bombardier C, Laine L, Burgos-Vargas R, et al. Response to expression of concern regarding VIGOR study. N Engl J Med 2006;354:1196 –1199. 15. Curfman GD, Morrissey S, Drazen JM. Expression of concern reaffirmed. N Engl J Med. 2006;354:1193. 16. FDA announces plan to strengthen advisory committee processes. FDA News, July 24, 2006. Available at: http://www. fda.gov/bbs/topics/NEWS/2006/NEW01416.html. Accessed August 25, 2006.
Address requests for reprints to: Michael Camilleri, MD, Mayo Clinic, Charlton 8-110, 200 First Street SW, Rochester, Minnesota 55905; e-mail: [email protected]; fax: (507) 255-5720. The authors wish to thank the associate editors of Clinical Gastroenterology and Hepatology and Gastroenterology for their valuable input to this commentary.
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