Study on failures to disclose conflicts of interest in Environmental Health Perspectives.

The Center for Science in the Public Interest (CSPI) recently investigated conflict of interest disclosures in a cross-section of leading scientific and medical journals, including EHP, to determine adherence to their own policies.

EHP's conflict of interest disclosure policy (EHP 2003) outlines a comprehensive list of "competing financial interests" that an author must disclose along with a published article. They include "grant support, employment (recent, present, or anticipated), ... travel, consultancies, advisory board positions, patent and royalty arrangements, stock shares, ... and the like." It limits disclosure to situations where an author "may gain or lose financially through publication." The editors also eschew any effort at enforcement, relying instead on the veracity of authors. EHP encourages its readers to scrutinize disclosure statements and offers to publish letters that address alleged inaccuracies.

During the study period of December 2003 through February 2004, EHP published 37 scientific studies. Only 2 of the studies indicated they were funded by industry, and only these 2 studies included conflict of interest disclosure statements for at least some of the authors.

The CSPI investigated the first and last authors involved in the 35 studies who did not disclose conflicts of interest. Our investigation revealed at least 3 articles (8.6%) where either the first or last authors should have disclosed conflicts in accordance with the disclosure policy.

First, a Procter and Gamble (P&G) scientist, William Owens, was identified only as a representative of the Organisation for Economic Co-operation and Development. The article (Yamasaki et al. 2003) validated an assay that may be used on P&G products. Owens did not disclose his corporate affiliation in this article, despite having disclosed his P&G employment in a previous EHP article (Owens and Koeter 2003).

Second, a Quebec, Canada, group led by Pierre Ayotte of CHUQ-Laval University Medical Center studied the effects of organochlorines and methyl mercury on a remote coastal population (Bilrha et al. 2003). Although there was no disclosure of a conflict of interest, the study was funded in part by the Canadian Network of Toxicology Centers, which is funded in part by the Canadian Chemical Producer Association, an industry trade group. Several of Ayotte's previous studies were funded in part by the Canadian Chemical Producer Association and the Canadian Chlorine Coordinating Committee, although Ayotte was not directly compensated for this work.

The third group of authors who did not disclose conflicts of interest are scientists at Macquarie University who investigated the sources of lead in children near a zinc-lead smelter (Gulson et al. 2004). Brian Gulson, a professor in Macquarie's graduate school of the environment, did not disclose that he is listed as an adviser on the website of a consulting group that advised Pasminco Ltd. (Laboratory Quality Management Services Pty Ltd. 2003), the company that ran the smelter. In a subsequent e-mail communication, Gulson informed the CSPI that one of his coauthors, Karen Mizon, was the wife of the owner of the consulting group.

In each of those cases, at least one of the authors of a study may gain financially from publication of the article, thus meeting the test of the EHP policy. Owens was directly employed by a company that might be affected by his findings. Gulson's colleagues stood to gain financially from a company directly affected by the subject matter of their articles.

Ayotte's study, although a borderline case, should have contained a disclosure statement because he had collaborated on industry-funded studies in the past and the study in question was funded by an industry-supported group. When a field of research is so closely tied to an industry, future funding for research may involve the goodwill of that industry. The spirit of conflict of interest disclosure is best served by full disclosure in such cases.

A fourth case of nondisclosure was not included in our results. In February 2004, EHP published a study funded by the National Institutes of Health that claimed polychlorinated biphenyls (PCBs) inhibit a receptor involved in clearing foreign substances from humans (Tabb et al. 2004). One of the authors, Bruce Blumberg, of the Department of Developmental and Cell Biology at the University of California, Irvine, is listed as a co-inventor on a patent granted in 2002 on the gene for an unrelated receptor in frogs. The use claimed for the frog gene is that it may be useful in identifying compounds that affect the receptor.

Should Blumberg disclose that patent as a potential conflict of interest? In an e-mail communication, he defended his failure to disclose by asking, "Do you seriously believe that a patent for a Xenopus (frog) nuclear receptor has any bearing on a paper about a mammalian receptor with an entirely different function?" Strict conflict of interest policies would argue "yes," because it is impossible to predict how the information in the new study will affect the use of previous knowledge or what inventions considered irrelevant today may be extremely useful (and lucrative) in the future. Even though EHP's policy (EHP 2003) says "may gain," we did not count his nondisclosure in our statistics.

Judging from the findings of our limited survey, a significant percentage of articles published in EHP (8.6%) fail to disclose relevant conflicts of interest of authors. We cannot determine whether authors are not disclosing the relevant information to EHP, or if they are providing the information but EHP is not publishing the disclosures. Considering the importance of providing readers with such information, it would seem that EHP needs to develop mechanisms to minimize failures to provide "full disclosure of competing financial interests" (EHP 2003). One possible mechanism for improving compliance would be for EHP not to accept for 3 years any papers submitted by authors who failed to disclose information about conflicts of interest.

I look forward to your response.

The author is employed as the director of the Integrity in Science Project at the Center for Science in the Public Interest.

REFERENCES

Bilrha H, Roy R, Moreau B, Belles-Isles M, Dewailly E, Ayotte P. 2003. In vitro activation of cord blood mononuclear cells and cytokine production in a remote coastal population exposed to organochlorines and methyl mercury. Environ Health Perspect 111:1952-1957:

EHP. 2003. Instructions to authors. Available: http://ehp. niehs.nih.gov/docs/admin/edpolicy.html [accessed 11 June 2004].

Gulson BL, Mizon KJ, Davis JD, Palmer JM, Vimpani G. 2004. Identification of sources of lead in children in a primary zinc-lead smelter environment. Environ Health Perspect. 112:52-60.

Laboratory Quality Management Services Pty Ltd. 2003. Brian L. Gulson--Consultant. Available: http://www.lqms.com.au/ information/expertise/brian.asp[accessed 11 June 2004].

Owens W, Koeter HBMW. 2003. The OECD special program to validate the rat uterotrophic bioassay: an overview. Environ Health Perspect 111:1527-1529.

Tabb MM, Kholodovych V, Grun F, Zhou C, Welsh WJ, Blumberg B. 2004. Highly chlorinated PCBs inhibit the human xenobiotic response mediated by the steroid and xenobiotic receptor (SXR). Environ Health Perspect 112:163-169.

Yamasaki K, Sawaki M, 0hta R, 0kuda H, Katayama S, Yamada T, et al. 2003. OECD validation of the Hershberger assay in Japan: phase 2 dose response of methyltestosterone, vinclozolin, and p,p'-ODE. Environ Health Perspect 111:1912-1919.

Merrill Goozner

Integrity in Science Project

Center for Science in the Public Interest

Washington, DC

E-mail: [e-mail]

Conflicts of Interest Owens' Response

To clarify comments from Goozner and the Center for Science in the Public Interest (CSPI), I would like to provide the pertinent facts on my compliance with EHP's policy on competing financial interest disclosure.

First, I was on loan or "seconded" from Procter & Gamble (P&G) to the Organisation for Economic Co-operation and Development (OECD) in Paris. The secondment was arranged at the request of the OECD, and I was officially under contract and employed by them from October 2002 through October 2003. I offer the former manager of the department, Herman Koeter; the current manager, Andrew Wagner; and their manager, Robert Visser, as references for these points.

Second, in this approximate period, I was a corresponding or contributing author on 11 relevant publications on assays that were either undergoing formal validation at the OECD or were being developed along similar lines for endocrine mechanisms (Ashby et al. 2002a, 2002b, 2003, 2004; Fang et al. 2003; Kanno et al. 2001, 2003a, 2003b; Owens and Ashby 2002; Owens and Koeter 2003; Owens et al. 2003; Yamasaki et al. 2003). In all cases but one, my P&G address was used.

Third, the one exception involved the article questioned by Goozner (Yamasaki et al. 2003). Kanji Yamasaki of the Chemical Evaluation and Research Institute in Japan was the corresponding author in this case. Because work on this manuscript (Yamasaki et al. 2003) occurred while I was at the OECD, Yamasaki used the OECD affiliation when submitting the manuscript to EHP. I simply did not notice the affiliation. If I had, I would have changed it to use my P&G affiliation to be consistent with the other 10 publications during this period.

Last, neither I nor P&G have any financial interest in the publications or their subject matter. Rather, this work was done to progress both development and validation work on safety tests that have potential for use to serve a diverse range of parties, including regulators, industry, and the public. Therefore, I do not see how allegations of a competing financial interest are valid in this case, even considering the oversight on the affiliation.

I hope this fully clarifies the record on this matter and lays the CSPI allegations to rest.

The author is employed by The Procter and Gamble Company.

REFERENCES

Ashby J, Lefevre PA, Tinwell H, Odum J, Owens W. 2004. Testosterone-stimulated weanling rats as a replacement for castrated rats in the Hershberger anti-androgen assay. Regul Toxicol Pharmacol 39:229-238.

Ashby J, Owens W, Deghenghi R, Odum J. 2002a. Concept evaluation: an assay for receptor-mediated and biochemical antiestrogens using pubertal rats. Regul Toxicol Pharmacol 35:393-397.

Ashby J, Owens W, Lefevre PA. 2002b. Concept evaluation: androgen-stimulated immature intact male rats as an assay for antiandrogens. Regul Toxicol Pharmacol 35:280-285.

Ashby J, Owens W, Odum J, Tinwell H. 2003. The intact immature rodent uterotrophic bioassay: possible effects on assay sensitivity of vomeronasal signals from male rodents and strain differences. Environ Health Perspect 111:1568-1510.

Fang H, Tong W, Branham W, Hung H, Xie Q, Moland CL, et al, 2003. Structure-activity relationships of 202 natural, synthetic and environmental chemicals for binding to the androgen receptor, Chem Res Toxicol 16:1338-1358.

Kanoo J, Onyon L, Haseman J, Fenner-Crisp P, Ashby J, Owens W. 2001. The OECD program to validate the rat uterotrophic bioassay to screen compounds for in vivo estrogenic responses: Phase 1. Environ Health Perspect 109:785-794.

Kanno J, Onyon L, Peddada S, Ashby J, Jacob E, Owens W. 2003. The OECD program to validate the rat uterotrophic bioassay. Phase 2: coded single dose studies. Environ Health Perspect 111:1550-1558.

Kanno J, Onyon L, Peddada S, Ashby J, Jacob E, Owens W. 2003. The OECD program to validate the rat uterotruphic bioassay. Phase 2: dose-response studies. Environ Health Perspect 111:1530-1549.

Owens JW, Ashby J. 2002. Critical review and evaluation of the uterotrophic bioassay for the identification of possible estrogen agonists and antagonists: in support of the validation of the OECD uterotrophic protocols for the laboratory rodent. CRC Crit Rev Toxicol 32:445-520.

Owens W, Koeter HBMW. 2003. The OECD special program to validate the rat uterotrophic bioassay: an overview. Environ Health Perspect 111:1527-1529.

Owens W, Ashby J, Odum J, Onyon L. 2003. The OECD program to validate the rat uterotrophic bioassay. Phase 2: dietary phytoestrogen analyses. Environ Health Perspect 111:1559-1567.

Yamasaki K, Sawaki M, Ohta R, Okuda H, Katayama S, Yamada T, et al. 2003. OECD validation of the Hershberger assay in Japan: phase 2 dose response of methyltestosterone, vinclozolin, and p,p'-DDE. Environ Health Perspect 111:1912-1919.

J. William Owens

The Procter and Gamble Company

Central Product Safety

Cincinnati, Ohio

E-mail: [e-mail]

Conflicts of Interest Ayotte's Response

Goozner contacted me by e-mail on 24 June 2004, and I promptly, honestly, and to the best of my knowledge answered questions regarding his claim that I did not disclose a conflict of interest while publishing our article (Bilrha et al. 2003) in EHP. Although I thought I made it clear that he was wrong in his allegations, he nevertheless chose to go ahead and include my name in a report published on the Center for Science in the Public Interest's (CSPI) website (CSPI 2004) and in his letter to EHP. Here are the facts.

In our 2003 manuscript (Bilrha et al. 2003), we acknowledged funding from the Canadian Network of Toxicology Centers (CNTC). As the corresponding author, I read the conflict of interest statement and indicated that I had nothing to declare, neither for me nor for the coauthors. I did not know at that time that the Canadian Chemical Producer Association was partly funding the CNTC. On their website (CNTC 2004), the CNTC indicates being funded mostly by public sources (90%) and does not mention the identity of private sources. In any case, had I known this at the time of publication, it would not have changed anything, because I never personally received any funds (or compensation of any sort, or stood to gain financially) from the Canadian Chemical Producer Association or the Canadian Chlorine Coordinating Committee. Goozner is wrong when he mentions that several of my previous studies were funded by these interest groups. I was a coauthor on two articles published previously in EHP, in which funding from these interest groups was acknowledged, along with other sources of funding (Sandau et al. 2000, 2002). I collaborated in the work, but I was not the recipient of funds obtained from the Canadian Chemical Producer Association or the Canadian Chlorine Coordinating Committee. Funds from these organizations went to the principal investigator at Carleton University, and not a penny was transferred to me.

I truly believe that the authors of scientific manuscripts should disclose relevant conflicts of interest, and I support enforcing disclosure by appropriate means. However, because Goozner elected to choose the easy way by conducting an Internet-based research, without actually talking to me, he wrongly associated my name with scientific misconduct. I am presently seeking legal advice on this matter.

The author declares he has no competing financial interests.

REFERENCES

Bilrba H, Roy R, Moreau B, Belles-Isles M, Dewailly E, Ayotte P. 2003. In vitro activation of cord blood mononuclear cells and cytokine production in a remote coastal population exposed to organocblorines and methyl mercury. Environ Health Perspect 111:1952-1957.

CNTC. 2064. Canadian Network of Toxicology Centres. Available: http://www.uoguelph.ca/cntc/ [accessed 21 July 2004].

CSPI. 2004. Unrevealed: Non-Disclosure of Conflicts of Interest in Four Leading Medical and Scientific Journals. Washington, DC:Center for Science in the Public Interest. Available: http://cspinet.org/new/pdf/unrevealed_final.pdf [accessed 15 July 2004].

Sandau CD, Ayotte P, Dewailly E, Duffe J, Norstrom RJ. 2000. Analysis of hydroxylated metabolites of PCBs (OH-PCBs) and other chlorinated phenolic compounds in whole blood from Canadian Inuit. Environ Health Perspect 108:611-616.

Sandau CD, Ayotte P, Dewailly E, Duffe J, Norstrom RJ. 2002. Pentachlorophenol and hydroxylated polychlorinated biphenyl metabolites in umbilical cord plasma of neonates from coastal populations in Quebec. Environ Health Perspect 110:411-417.

Pierre Ayotte

Public Health Research Unit

CHUQ-Laval University Medical Center

Quebec, Canada

E-mail: [e-mail]

Conflicts of Interest Gulson's Response

We commend the Center for Science in the Public Interest (CSPI) for their investigation into conflicts of interest statements in leading scientific and medical journals, but we take exception to our inclusion (Gulson et al. 2004) as an example of providing misinformation to EHP.

Goozner's sweeping statement that my colleague had previously received research funding, compensation, or stood to gain financially from Pasminco Ltd. is highly inaccurate. We received no research funding, compensation, or financial gain from the company to undertake this study. In fact, if Goozner had read even the abstract of our article, he would have noted that the findings were detrimental to the company, as the dominant source of lead in the environment and children probably derived from smelter emissions. Furthermore, the smelter closed in September 2003 and the company no longer exists. With respect to the association of my colleague, Karen Mizon, to her husband's company and the (consulting) work undertaken for Pasminco Ltd., the work [an International Organization for Standardization (ISO) Guide 25 accreditation assessment of the company's on-site laboratory (ISO/International Electrotechnical Commission 1990)] was undertaken by the owner for the accreditation body while he was employed by a federal government research organization, and he was not paid for this audit.

The author declares he has no competing financial interests.

REFERENCE

Gulson BL, Mizen KJ, Davis JD, Palmer JM, Vimpani G. 2064. Identification of sources of lead in children in a primary zinc lead smelter environment. Environ Health Perspect 112:52-60.

ISO/International Electrotechnical Commission. 1990. ISO Guide 25: General Requirements for the Competence of Calibration and Testing Laboratories. 3rd ed. Geneva: International Organization for Standardization.

Brian Gulson

Graduate School of the Environment

Macquarie University

Sydney, New South Wales, Australia

E-mail: [e-mail]