Conflicts of interest, authorship, and disclosures in industry-related scientific publications: the tort bar and editorial oversight of medical journals.

Abstract

In recent years, Mayo Clinic Proceedings has published a variety of articles dealing with important, broad-reaching matters of societal interest that impact medicine and patient care. Topics included ideal physician behaviors, gender and medical career mentoring, advance directives and end-of-life issues, physician involvement in capital punishment, and, germane to this article, institutional conflicts of interest (COIs), as well as the journal's approach to publication of industry-sponsored clinical research.1Menaker R Bahn RS How perceived physician leadership behavior affects physician satisfaction.Mayo Clin Proc. 2008; 83: 983-988Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 2Lanier WL Rose SH The contemporary medical community: leadership, mentorship, and career choices [editorial].Mayo Clin Proc. 2008; 83: 974-977Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar, 3Mayer AP Files JA Ko MG Blair JE Academic advancement of women in medicine: do socialized gender differences have a role in mentoring?.Mayo Clin Proc. 2008; 83: 204-207Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar, 4Sherazi S Daubert JP Block RC et al.Physicians' preferences and attitudes about end-of-life care in patients with an implantable cardioverter-defibrillator.Mayo Clin Proc. 2008; 83: 1139-1141Abstract Full Text Full Text PDF PubMed Scopus (62) Google Scholar, 5Cohen NH Advance directives: know what you want, get what you need [editorial].Mayo Clin Proc. 2007; 82: 1460-1462Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar, 6Waisel D Physician participation in capital punishment.Mayo Clin Proc. 2007; 82: 1073-1082Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 7Caplan AL Should physicians participate in capital punishment?.Mayo Clin Proc. 2007; 82: 1047-1048Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 8Lanier WL Berge KH Physician involvement in capital punishment: simplifying a complex calculus.Mayo Clin Proc. 2007; 82: 1043-1046Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar, 9Camilleri M Cortese DA Managing conflict of interest in clinical practice.Mayo Clin Proc. 2007; 82: 607-614Abstract Full Text Full Text PDF PubMed Scopus (20) Google Scholar, 10Stossel TP Divergent views on managing clinical conflicts of interest [letter].Mayo Clin Proc. 2007; 82: 1013-1014Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 11Romano TJ Divergent views on managing clinical conflicts of interest [letter].Mayo Clin Proc. 2007; 82: 1013-1014Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 12Camilleri M Cortese DA Divergent views on managing clinical conflicts of interest [letter reply].Mayo Clin Proc. 2007; 82: 1014-1015Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 13Holtby S Wakewich P Publication of market-driven research in medical journals [letter].Mayo Clin Proc. 2006; 81: 850Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar, 14Yawn BP Publication of market-driven research in medical journals [letter reply].Mayo Clin Proc. 2006; 81: 850-851Abstract Full Text Full Text PDF PubMed Scopus (1) Google Scholar, 15Lanier WL Editor's note: industry support of articles published in Mayo Clinic Proceedings.Mayo Clin Proc. 2006; 81: 851-852Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar Equally important to the well-being of patients and of medicine is the legitimacy of interactions between industry sponsors of research and investigator-authors who communicate the information and the journals/editors who review and ultimately determine publication of the material. In this age of transparency, disclosure of COIs has assumed great prominence in medical journals. However, transparency is not always clear, disclosure policies are varied, and their implementation (by journals and medical societies) is asymmetric and biased. This commentary examines some prominent recent actions by consultants to plaintiffs' attorneys and a series of publications in 3 top-tier general medical journals that illustrate selective and incomplete disclosure of conflicts—both financial and otherwise. In my view, these events call into question actions by a medical specialty society with one of the consultants and, more broadly, the editorial practices at the journals concerning COIs. Specific recommendations are offered to address the latter. In April 2008, the Journal of the American Medical Association (JAMA) published a “research” article by Ross, Hill, Egilman, and Krumholz16Ross JS Hill KP Egilman DS Krumholz HM Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation.JAMA. 2008; 299: 1800-1812Crossref PubMed Scopus (337) Google Scholar that was based on materials obtained through legal discovery; the authors claimed that Merck & Co, Inc (Whitehouse Station, NJ) previously hired professional writers (termed ghostwriters) to draft papers concerning clinical trials of rofecoxib (Vioxx) and invited academic physicians to accept authorship of them (without acknowledgment of the compensated writing) to increase their credibility. These guest authors supposedly made little contribution to the research, analysis, or interpretation of the data, an unacceptable practice. Many of the articles were from the mid- to late 1990s. JAMA issued press releases and an accompanying editorial17DeAngelis CD Fontanarosa PB Impugning the integrity of medical science: the adverse effects of industry influence [editorial].JAMA. 2008; 299: 1833-1835Crossref PubMed Scopus (205) Google Scholar that berated medical product companies broadly for manipulating clinical research, with resulting widespread media coverage. Some other journals opposed JAMA's posture.18Nature Publishing Group Nothing to see here: based on one company's past poor publishing practices, a top-tier medical journal misguidedly stigmatizes any paper from industry [editorial].Nat Biotechnol. 2008; 26: 476Crossref PubMed Scopus (2) Google Scholar Several direct responses to JAMA by authors of publications listed in the article pointed out lapses in the report by Ross et al and mistaken inclusion of their publications in the analysis, with predictable rejoinders by the authors and editors.19Fitzgerald GA Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 900-901Crossref PubMed Scopus (1) Google Scholar, 20Patrono C Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 901Crossref PubMed Scopus (1) Google Scholar, 21Hawkey CJ Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 901Crossref PubMed Scopus (1) Google Scholar, 22Ferris S Galasko D Kirby L Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 901-902PubMed Google Scholar, 23Ong HT Cheah JS Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 903-904Crossref PubMed Google Scholar, 24Ross JS Egilman DS Harlan M Krumholz HM Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter reply].JAMA. 2008; 300: 904-905Crossref PubMed Scopus (1) Google Scholar, 25DeAngelis CD Fontanarosa PB Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter reply].JAMA. 2008; 300: 905-906Crossref Scopus (3) Google Scholar One letter23Ong HT Cheah JS Guest authorship, mortality reporting, and integrity in rofecoxib studies [letter].JAMA. 2008; 300: 903-904Crossref PubMed Google Scholar suggested that “an author's declaration of financial dealings with industry is only meaningful if the monetary value received from each company over a preceding period (perhaps the past 2 years) is clearly stated,” a point to which I will return. I have worked in both academia and industry, including more than 17 years through 2006 at Merck, primarily in clinical drug development. From 2001 to 2006, this included management of a department of medical writers, support staff, and statisticians who worked with Merck scientists and external investigators to publish many (although not all) articles related to mid- and late-phase clinical trials sponsored by Merck. We adhered to the authorship criteria of the ICMJE (International Committee of Medical Journal Editors) and acknowledged lesser contributions to manuscripts by persons who did not meet those criteria. (The ICMJE states that, “Authorship credit should be based on (1) substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; (2) drafting the article or revising it critically for important intellectual content; and (3) final approval of the version to be published. Authors should meet conditions 1, 2, and 3.”)26International Committee of Medical Journal Editors Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication: updated October 2008. ICMJE Web site.www.icmje.orgGoogle Scholar These criteria are widely used in biomedical research, although by no means universally. Speaking only for myself, and in no way as a spokesperson, this is not a defense of Merck or of actions related to Vioxx. However, readers may have a different perspective concerning the report of supposed authorship misconduct by Merck when they learn what was not disclosed by Ross et al or by JAMA. That article16Ross JS Hill KP Egilman DS Krumholz HM Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation.JAMA. 2008; 299: 1800-1812Crossref PubMed Scopus (337) Google Scholar (and the others discussed subsequently) illustrates the far-reaching influence of the American tort bar,27Berenson A Trial lawyers are now focusing on lawsuits against drug makers.New York Times. May 18, 2003; (Accessed July 8, 2009.)http://www.nytimes.com/2003/05/18/us/trial-lawyers-are-now-focusing-on-lawsuits-against-drug-makers.htmlGoogle Scholar now impacting the content of important medical journals to further its litigation interests, abetted by journal editors who appear biased against industry. Consider today's environment. There is a politically correct herd mentality that ascribes to the concept that objectivity is forsaken by medical companies that seek profit (and by their employees) because of “conflict of interest.” A COI has been defined as “a set of conditions in which professional judgment concerning a primary interest (such as a patient's welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain).”28Thompson DF Understanding financial conflicts of interest.N Engl J Med. 1993; 329: 573-576Crossref PubMed Scopus (625) Google Scholar Previously, the president of the Association of American Medical Colleges emphasized that the term indicates a state of affairs and not a behavior, that COIs are ubiquitous, and that despite their inaccurate portrayal by the media, COIs do not indicate the occurrence of any improper behavior, much less scientific misconduct, analogous to a state of potential energy.29Cohen JJ Trust us to make a difference: ensuring public confidence in the integrity of clinical research.Acad Med. 2001; 76: 209-214Crossref PubMed Scopus (40) Google Scholar The editors of JAMA also wrote, “Conflicts of interest represent the potential for biased judgment, but are not [emphasis added] an indicator of the likelihood or certainty that such judgments or compromises will occur.”30DeAngelis CD Fontanarosa PB Flanagin A Reporting financial conflicts of interest and relationships between investigators and research sponsors [editorial].JAMA. 2001; 286: 89-91Crossref PubMed Scopus (107) Google Scholar Indeed, in its recently published report on COI in medical research, education, and practice, the Institute of Medicine defined COI as “A set of circumstances that creates a risk [emphasis added] that professional judgment or actions regarding a primary interest will be unduly influenced by a secondary interest.”31Conflict of interest in medical research, education, and practice.in: Institute of Medicine of the National Academies Web site. National Academies Press, Washington, DC2009http://www.iom.edu/CMS/3740/47464/65721.aspxGoogle Scholar Editors at The Lancet and the British Medical Journal (BMJ) similarly noted that finance is only one of many issues that can lead to COI; other factors such as publication pressure, prestige, scientific reputation, career advancement, and even religion can be more potent than dollars in potentially biasing a researcher.32Horton R Conflicts of interest in clinical research: opprobrium or obsession?.Lancet. 1997; 349: 1112-1113Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 33Smith R Conflict of interest and the BMJ: time to take it seriously [editorial].BMJ. 1994; 308: 4-5Crossref PubMed Scopus (34) Google Scholar Yet today there is a McCarthyesque reaction to the term, conflict of interest, with an unstated presumption of guilt until proven innocent. What led to this? The reputation of the pharmaceutical industry, once among the highest ranked by the public, has plummeted and is now similar to that of financial and insurance companies and lower than that of the automotive industry.34Harris Interactive The 9th annual RQ: reputations of the 60 most visible companies: a survey of the US general public. HarrisInteractive Web site.www.harrisinteractive.com/news/mediaaccess/2008/HI_BSC_REPORT_AnnualRQ_USASummary07-08.pdfGoogle Scholar A small number of highly publicized incidents occurred in the mid-1990s and early 2000s that involved frankly egregious attempts to manipulate publication of clinical research in ways that would favor the sponsor's product. These included blocking publication by contractual means,35Dong BJ Hauck WW Gambertoglio JG et al.Bioequivalence of generic and brand-name levothyroxine products in treatment of hypothyroidism.JAMA. 1997; 277: 1205-1213Crossref PubMed Google Scholar, 36Rennie D Thyroid storm [editorial].JAMA. 1997; 277: 1238-1243Crossref PubMed Google Scholar withholding study data from a principal investigator,37Kahn JO Cherng DW Mayer K Murray H Lagakos S Evaluation of HIV-1 immunogen, an immunologic modifier, administered to patients infected with HIV having 300 to 549 × 106/L CD4 cell counts: a randomized controlled trial.JAMA. 2000; 284: 2193-2202Crossref PubMed Scopus (155) Google Scholar and reporting a 12-month study as a 6-month trial that provided a misleadingly favorable profile of the drug without explanation of the changed reporting period.38Silverstein FE Faich G Goldstein JL et al.Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: a randomized controlled trial.JAMA. 2000; 284: 1247-1255Crossref PubMed Scopus (3092) Google Scholar, 39Hrachovec JB Mora M Reporting of 6-month vs 12-month data in a clinical trial of celecoxib [letter].JAMA. 2001; 286: 2398Crossref PubMed Scopus (27) Google Scholar In 2001, the ICMJE published a policy/editorial, “Sponsorship, Authorship, and Accountability,” that specified principles for investigators working with industry to ensure investigator access to study data and control of the decision to publish study results.40Davidoff F DeAngelis CD Drazen JM et al.Sponsorship, authorship, and accountability [editorial].Ann Intern Med. 2001; 135: 463-466Crossref PubMed Scopus (46) Google Scholar Less than 3 years later, reports appeared of a sponsor allegedly suppressing publication of placebo-controlled clinical studies that failed to demonstrate efficacy of a selective serotonin reuptake inhibitor antidepressant in adolescents; the studies also raised questions (difficult to quantify) about possible adverse effects of the drug/drug class on suicidal ideation.41The Lancet Depressing research [editorial].Lancet. 2004; 363: 1335Abstract Full Text Full Text PDF PubMed Scopus (41) Google Scholar, 42Martinez B Spitzer charges Glaxo concealed Paxil data.The Wall Street Journal. June 3, 2004; (Accessed July 8, 2009.): B1http://www.moralgroup.com/NewsItems/Drugs/p3.htmGoogle Scholar These events led to the ICMJE's initial call for mandatory clinical trial registration in September 2004.43DeAngelis C Drazen JM Frizelle FA et al.Clinical trial registration: a statement from the International Committee of Medical Journal Editors [editorial].Lancet. 2004; 364: 911-912http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=15364170&dopt=AbstractAbstract Full Text Full Text PDF PubMed Scopus (233) Google Scholar Merck voluntarily withdrew Vioxx from the market later that month; although close in timing, the 2 events were unrelated. On December 8, 2005, an “Expression of Concern” was published online by The New England Journal of Medicine (NEJM), suggesting incomplete reporting of serious adverse cardiovascular events in a gastrointestinal safety outcome study of rofecoxib originally published in 2000,44Curfman 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. 2000;343:1520-8 [editorial].N Engl J Med. 2005; 353 (Epub 2005 Dec 8.): 2813-2814Crossref PubMed Scopus (118) Google Scholar although the validity of those concerns as well as circumstances and timing of the NEJM statement have been challenged.45Bombardier C Laine L Burgos-Vargas R et al.Response to expression of concern regarding VIGOR study [letter].N Engl J Med. 2006; 354 (Epub 2006 Feb 22.): 1196-1199Crossref PubMed Scopus (30) Google Scholar, 46Reicin A Shapiro D Response to expression of concern regarding VIGOR study [letter].N Engl J Med. 2006; 354 (Epub 2006 Feb 22.): 1198-1199Google Scholar, 47Armstrong D 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.”.The Wall Street Journal (East Ed). 2006; (A10.): A1Google Scholar All these events doubtless contributed to passage of Title VIII (Section 801) of the Food and Drug Administration Act of 2007, known as FDAAA,48US Department of Health and Human Services. Food and Drug Administration Food and Drug Administration Amendments Act of 2007, P.L. 110-85.http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=110_cong_public_laws&docid=f:publ085.110Google Scholar, 49Hirsch L Trial registration and results disclosure: impact of US legislation on sponsors, investigators, and medical journal editors.Curr Med Res Opin. 2008; 24 (Epub 2008 May 6.): 1683-1689Crossref PubMed Scopus (22) Google Scholar making it federal law to register most interventional clinical trials at outset and to disclose trial results (for marketed products) by 12 months after study completion, on www.clinicaltrials.gov. Other studies have reported that industry sponsorship of clinical research is related to a higher frequency of positive outcomes that favor the sponsor's intervention50Bekelman JE Li Y Gross CP Scope and impact of financial conflicts of interest in biomedical research: a systematic review.JAMA. 2003; 289: 454-465Crossref PubMed Scopus (1453) Google Scholar, 51Lexchin J Bero LA Djulbegovic B Clark O Pharmaceutical industry sponsorship and research outcome and quality: systematic review.BMJ. 2003; 326: 1167-1170Crossref PubMed Scopus (1623) Google Scholar or positive conclusions,52Kjaergard LL Als-Nielsen B Association between competing interests and authors' conclusions: epidemiological study of randomised clinical trials published in the BMJ.BMJ. 2002; 325: 249Crossref PubMed Google Scholar although it is difficult to see how the latter can be assessed in a neutral manner. Publication bias (preferential publication of studies with positive outcomes vs trials with negative, neutral, or ambiguous outcomes) has been reported for more than 2 decades,53Montori VM Smieja M Guyatt GH Publication bias: a brief review for clinicians.Mayo Clin Proc. 2000; 75: 1284-1288Abstract Full Text Full Text PDF PubMed Scopus (121) Google Scholar and industry is frequently criticized for contributing to this phenomenon. However, one analysis showed that large randomized trials with pharmaceutical sponsorship that were presented at a major oncology meeting were published sooner than those sponsored by cooperative groups or those in which sponsorship was not indicated54Krzyanowska MK Pintilie M Tannock IF Factors associated with failure to publish large randomized trials presented at an oncology meeting.JAMA. 2003; 290: 495-501Crossref PubMed Scopus (271) Google Scholar; publication bias clearly extends to government- and nonprofit-funded research.55Chan AW Krleza-Jerić K Schmid I Altman DC Outcome reporting bias in randomized trials funded by the Canadian Institutes of Health Research.CMAJ. 2004; 171: 735-740PubMed Google Scholar, 56Hirsch L Randomized clinical trials: what gets published, and when?.CMAJ. 2004; 170: 481-483PubMed Google Scholar A different type of publication bias, whereby only selected outcomes within study protocols are reported in the published article (ie, positive outcomes are elevated and negative or border-line results demoted or neglected), has been described.57Chan AW Hróbjartsson A Haahr MT Gøtzsche PC Altman DC Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.JAMA. 2004; 291: 2457-2465Crossref PubMed Scopus (1402) Google Scholar This analysis also failed to show any relationship between funding source and reporting of biased results.57Chan AW Hróbjartsson A Haahr MT Gøtzsche PC Altman DC Empirical evidence for selective reporting of outcomes in randomized trials: comparison of protocols to published articles.JAMA. 2004; 291: 2457-2465Crossref PubMed Scopus (1402) Google Scholar Nevertheless, it is not difficult to understand a degree of extra scrutiny of industry-sponsored research by reviewers and editors, but the extent and the method of doing so are important to ensure that work deserving publication is not censored. About 4 years ago, JAMA started requiring that only for papers describing industry-sponsored studies that were analyzed by a company statistician, the sponsor had to provide the raw data to an “independent” academic biostatistician (paid by the sponsor of course) to confirm the analyses, before it would consider the paper for publication.58Fontanarosa PB Flanagin A DeAngelis CD Reporting conflicts of interest, financial aspects of research, and role of sponsors in funded studies [editorial].JAMA. 2005; 294: 110-111Crossref PubMed Scopus (116) Google Scholar Reaction to this policy was almost uniform: statistical societies and industry organizations alike protested the unspoken but clear demeaning of industry scientists' integrity,59Loew CJ Conflicts of interest and independent data analysis in industry-funded studies [letter].JAMA. 2005; 294: 2575Crossref PubMed Scopus (8) Google Scholar, 60Molenberghs G Imrey P Drake C Conflicts of interest and independent data analysis in industry-funded studies [letter].JAMA. 2005; 294: 2575-2576Crossref PubMed Google Scholar with no change by JAMA.61Fontanarosa PB DeAngelis CD Conflicts of interest and independent data analysis in industry-funded studies [letter reply].JAMA. 2005; 294: 2576-2577Crossref Google Scholar Prominent editors and biostatisticians strongly criticized the policy.62Rothman KJ Evans S Extra scrutiny for industry funded trials: JAMA's demand for an additional hurdle is unfair—and absurd.BMJ. 2005; 331: 1350-1351Crossref PubMed Scopus (24) Google Scholar A number of companies stopped submitting manuscripts to JAMA because of the policy. In an editorial revealingly titled, “The Influence of Money on Medical Science,”63DeAngelis CD The influence of money on medical science [editorial].JAMA. 2006; 296 (Epub 2006 Aug 7.): 996-998Crossref PubMed Scopus (71) Google Scholar the JAMA editor stated that any company doing so “… risks not only the perception that the company may have something to hide, but the reputation of any researcher willing to accede to such a company demand.” The pejorative implications of this policy rationalization were clear. At Merck, the situation was discussed with investigators, who per company guidelines had final authority over manuscript submission decisions, and they fully supported pursuing publication of some major clinical trials elsewhere than JAMA—there were no company “demands.” Colleagues at other companies reported identical experiences (personal communications). In the end, JAMA's policy is a clear example of bias in manuscript review and provides no real benefit to its readers. Medical journals today differ widely in their approach to disclosures of COI. Requests for uniform COI disclosure policies have been made,64Goozner M Caplan A Moreno J Kramer BS Babor TF Cowles Husser W A common standard for conflict of interest disclosure. Center for Science in the Public Interest Web site.http://www.cspinet.org/new/pdf/20080711_a_common_standard_for_conflict_of_interest_disclosure__final_for_conference.pdfGoogle Scholar, 65Califf R The changing academic landscape. Presented at: 4th Annual Meeting of the International Society for Medical Publication Professionals; Philadelphia, PA.http://www.ismpp.org/pdf/4th%20Annual%20Meeting%20Highlights%20Newsletter%20FINAL.PDFDate: April 28-30, 2008Google Scholar without noticeable impact. JAMA is one of the most stringent in enacting its policy for disclosure of financial COI, which appears to apply especially to any type of paid relationship with industry. For example, in 2006 JAMA published an important National Institutes of Health (NIH) observational study that showed benefits of continued antidepressant use in pregnant women.66Cohen LS Altshuler LL Harlow BL et al.Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment.JAMA. 2006; 295: 499-507Crossref PubMed Scopus (758) Google Scholar After news reports that JAMA's COI disclosure rules had not been followed, JAMA forced public apologies and corrected disclosures from the authors regarding their financial relationships with multiple manufacturers of antidepressants (which the authors thought irrelevant because of the NIH sponsorship and observational nature of the study).67Cohen LS Nonacs R Viguera AC et al.Antidepressant treatment and relapse of depression during pregnancy [letter reply].JAMA. 2006; 296: 166-167Crossref PubMed Scopus (3) Google Scholar JAMA also requested what it called corrective actions by deans of the authors' medical schools.68Armstrong D Financial ties to industry cloud major depression study: at issue: whether it's safe for pregnant women to stay on medication: JAMA asks authors to explain.The Wall Street Journal (East Ed). July 11, 2006; (A9) (Acccessed July 8, 2009.): A1http://research.unm.edu/coi/private/Articles/WSJ%202006.07.11%20Fin%20Ties%20Industry.pdfGoogle Scholar, 69Armstrong D JAMA to tighten rules on author disclosure.The Wall Street Journal. July 12, 2006; (Accessed April 18, 2009.)http://online.wsj.com/article/SB115266504840504116-search.html?KEYWORDS=david+armstrong&COLLECTION=wsjie/6monthGoogle Scholar Yet, JAMA's editor simultaneously affirmed that the publication was still valid because it had passed peer review,63DeAngelis CD The influence of money on medical science [editorial].JAMA. 2006; 296 (Epub 2006 Aug 7.): 996-998Crossref PubMed Scopus (71) Google Scholar raising questions about the intense reaction to the supposed “infractions.” In March 2009, a similar situation ensued. According to multiple reports in the Wall Street Journal, 2 editors of JAMA allegedly threatened and intimidated a neuroanatomist at a small university medical center and the dean of the school because the professor posted a letter on the Web site of BMJ70Leo J Lacasse J Clinical trials of therapy versus medication: even in a tie, medication wins [letter].http://www.bmj.com/cgi/eletters/338/feb05_1/b463#208503Google Scholar that raised questions about the reporting of a trial's results and about undisclosed financial COI by authors of the article originally published in JAMA, 5 months after bringing this to the attention of the JAMA editor.71Armstrong D The Wall Street Journal Health Blog. JAMA editor calls critic a “nobody and a nothing.”.http://blogs.wsj.com/health/2009/03/13/jama-editor-calls-critic-a-nobody-and-a-nothing/Date: March 13, 2009Google Scholar JAMA demanded that the author retract the letter in BMJ.72Armstrong D Medical journal decries public airing of conflicts.The Wall Street Journal. March 22, 2009; (Accessed July 8, 2009.)http://online.wsj.com/article/SB123776823117709555.html#articleTabs%3DarticleGoogle Scholar Nonprofit groups normally critical of industry called for investigations of the editors, and JAMA's editorial oversight committee was reportedly doing so.73Armstrong D Nonprofit hits JAMA editors, urges inquiry.The Wall Street Journal. March 27, 2009; (Accessed July 8, 2009.)http://online.wsj.com/article/SB123810131860651487.htmlGoogle Scholar, 74Armstrong D Medical group seeks probe of its journal.The Wall Street Journal. March 28, 2009; (Accessed July 8, 2009.)http://online.wsj.com/article/SB123819137827260883.htmlGoogle Scholar The cause of the uproar? Modest honoraria (about $3000) that had been accepted 4 years previously for 2 talks, apparently forgotten by the lead author,75Robinson RG Re: Clinical trials of therapy versus medication: even in a tie, medication wins [letter reply].http://www.bmj.com/cgi/eletters/338/feb05_1/b463#208503Google Scholar from the company that markets the drug studied (the company had no role in the design, conduct, or analysis of the NIH-funded study). JAMA responded by issuing online a new policy on COI disclosures, requiring whistle-blowers to essentially agree to be gagged until JAMA completes its investigation of alleged COI.76DeAngelis CD, Fontanarosa PB. Conflicts over conflicts of interest [published online ahead of print March 20, 2009] [editorial]. JAMA doi:10.1001/jama.2009.480.Google Scholar Other editors criticized this approach, one calling the new policy “a dangerous position.”72Armstrong D Medical journal decries public airing of conflicts.The Wall Street Journal. March 22, 2009; (Accessed July 8, 2009.)http://online.wsj.com/article/SB123776823117709555.html#articleTabs%3DarticleGoogle Scholar In July 2009, JAMA updated its policy on addressing unreported COI, saying that it will “explain” to the person raising such allegations the value of maintaining confidentiality while JAMA's investigation is under way,77DeAngelis CD Fontanerosa PB Resolving unreported conflicts of interest [editorial].JAMA. 2009; 302: 198-199Crossref PubMed Scopus (28) Google Scholar as opposed to requiring it. According to the Wall Street Journal, the change came about after the JAMA editorial oversight committee presented recommendations to the board of the AMA (American Medical Association). 78Armstrong D. Medical journal eases rule silencing filers of complaints. July 7, 2009. The Wall Street Journal.com http://online.wsj.com/article/SB124700923018308521.html. Accessed July 13, 2009.Google Scholar Both JAMA and the AMA declined to comment; the AMA said “…it is an internal matter…”78Armstrong D. Medical journal eases rule silencing filers of complaints. July 7, 2009. The Wall Street Journal.com http://online.wsj.com/article/SB124700923018308521.html. Accessed July 13, 2009.Google Scholar In any case, this is far from the supposed mission of medical journals to communicate scientific information and educate their readers on new advances in biomedical research, while providing informed commentary on such developments. JAMA issued a strident editorial in 2008 that accompanied the rofecoxib-related ghostwriting article by Ross et al16Ross JS Hill KP Egilman DS Krumholz HM Guest authorship and ghostwriting in publications related to rofecoxib: a case study of industry documents from rofecoxib litigation.JAMA. 2008; 299: 1800-1812Crossref PubMed Scopus (337) Google Scholar (and a second article in the same issue, also based on materials from legal discovery, that concluded that Merck had failed to properly report mortality data to the Food and Drug Administration [FDA] in certain rofecoxib clinical trials79Psaty BM Kronmal RA Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment: a case study based on documents from rofecoxib litigation.JAMA. 2008; 299: 1813-1817Crossref PubMed Scopus (142) Google Scholar). JAMA declared “…all journals must disclose all pertinent relationships of all authors with any for-profit companies”…, “must seriously consider funding sources and authors' disclosed financial conflicts of interest and financial relationships when deciding whether to publish a study or review,” [emphasis added] and, “For-profit companies… should not be solely or primarily involved in collecting and monitoring of data, in conducting the data analysis, and in preparing the manuscript reporting study results.”17DeAngelis CD Fontanarosa PB Impugning the integrity of medical science: the adverse effects of industry influence [editorial].JAMA. 2008; 299: 1833-1835Crossref PubMed Scopus (205) Google Scholar The latter proviso is prejudiced and untenable for any company that is developing a new drug, biologic, or device because the company must reach á priori agreement with the FDA on all aspects of study design, conduct, data collection, end point adjudication (if applicable), data analysis, and reporting. In other words, companies need close involvement in all these important clinical trial functions for preregistration studies. Sponsor function in postregistration trials varies; it may be minimal for some investigator-initiated studies or substantial for other company-initiated research. Blanket mandates regarding sponsor involvement in clinical trials are not useful.