ScienceWeek

SCIENCE POLICY: ON DISCLOSURE IN REGULATORY SCIENCE

The following points are made by D. Michaels and W. Wagner (Science 2003 302:2073):

1) There is substantial divergence between the scientific community's standards for ensuring research integrity and the ad hoc protections for researcher independence tolerated by federal regulatory agencies. The biomedical community's concern about potential conflicts of interest is addressed in the widespread (1,2) policy of journals to require that authors of submitted articles disclose financial relationships so that editors and readers can judge whether conclusions might have been influenced by those financial ties. The editors of 13 leading biomedical journals have gone further and declared that they will no longer publish articles based on studies done under contracts in which the investigators did not have the unfettered right to publish the findings (1).

2) With the increased involvement of universities in commercial enterprises and collaborations, conflicts-of-interest concerns at academic institutions have grown in importance. In response, many institutions have implemented policies that attempt to ensure independence and protect the ability of researchers to share data with fellow scientists and the public (3-5).

3) Research independence is also of great importance to regulators. Federal agencies charged with protecting the public's health rely out of necessity on scientific evidence submitted by private parties in determining the hazardous characteristics of products and wastes. At the same time, there is growing evidence of conflicts of interest in private research submitted for regulation. For example, there are reports of a "funding effect", with sponsorship associated with favorable findings (3). There are also accounts of improper sponsor control over the design and reporting of results, and sponsor suppression or termination of research showing adverse effects.

4) Except for limited prohibitions against the suppression of adverse effects, however, the quality and independence of private research used for regulation is subject to considerably less oversight than corresponding federally funded research. Most significantly, private research submitted for regulatory purposes escapes external scrutiny if the research or the chemical under study is claimed to be confidential business information. Most of the applications submitted to the U.S. Environmental Protection Agency (EPA) to market new chemicals, for example, contain science-relevant information that industry claims is confidential. Many of these trade secret claims do not appear to be justified. Yet without this information, it is not possible to evaluate the regulators' decisions.

5) Even when sponsored research is not protected as trade secrets, the data underlying privately submitted research used for regulation need not be made publicly available, as is required for its federally funded counterpart. Also in contrast to public research, private research is not subject to the scientific misconduct regulations promulgated by the U.S. Office of Research Integrity. Finally, even the "Data Quality Act", which ostensibly is an attempt to improve the quality of regulatory science through a formal complaint process, exempts a great deal of private research from its coverage.

6) Despite the evident value of transparency about sponsorship in regulatory science, the disclosure of sponsor influence is generally not required or even requested by federal regulatory agencies. The EPA, the Occupational Safety and Health Administration, the Mine Safety and Health Administration, the Consumer Product Safety Commission, and the National Highway Traffic Safety Administration have no formal mechanisms to identify potential conflicts of interest, nor do they provide any incentive to encourage the conduct of research that is free of sponsor control.

References (abridged):

1. Uniform Requirements for Manuscripts Submitted to Biomedical Journals, www.ICMJE.org (October 2001)

2. F. Davidoff et al., JAMA 286, 1232 (2001)

3. S. Krimsky, Science in the Private Interest: Has the Lure of Profits Corrupted the Virtue of Biomedical Research? (Rowman & Littlefield, Lanham, MD, 2003)

4. U.S. General Accounting Office, "Biomedical research: HHS direction needed to address financial conflicts of interest" (GAO-02-89, Government Printing Office, Washington, DC, 2001)

5. M. K. Cho et al., JAMA 284, 2203 (2000)

Science http://www.sciencemag.org

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FINANCIAL TIES AND CONFLICTS OF INTEREST BETWEEN PHARMACEUTICAL AND TOBACCO COMPANIES

The following points are made by B. Shamasunder and L. Bero (J. Am. Med. Assoc. 2002 288:738):

1) Financial ties between companies producing addictive tobacco products and companies producing drugs to treat or alleviate the addiction are a potential conflict of interest. Several types of financial ties can exist. For example, one company could be the sole supplier of a product that is needed by another company. Or, a company could be financially dependent on sales from another company. Corporate diversification also results in financial ties between companies.

2) Corporate diversification leads to a network of holding companies, parent companies, and subsidiaries that are financially connected but operate seemingly independently.(1-2) Diversification can contribute to financial stability, but it also allows corporate negotiations to occur with little public knowledge and can hide financial ties that are potential conflicts of interest.

3) The diversification of the tobacco industry is well-documented.(3-4) The tobacco industry has systematically acquired companies that manufacture unrelated consumer products such as cookies, macaroni and cheese, candy, and pharmaceuticals. The tobacco industry has used its financial ties to pressure a variety of industries to oppose tobacco control.(5) The pharmaceutical industry also maintains diversified interests and is involved in the sale of multiple products such as chemicals, pesticides, plastics, and pharmaceuticals.(2) Thus, corporate diversification has resulted in financial ties between pharmaceutical companies that market nicotine replacement therapies (NRTs) and the tobacco industry.

4) In summary: Corporate diversification allows for well-hidden financial ties between pharmaceutical and tobacco companies, which can cause a conflict of interest in the development and marketing of pharmaceutical products. In their investigation of tobacco company documents released and posted on the Internet as a result of the Master Settlement Agreement, the authors report they have found that these financial ties have fostered both competition and collaboration between the tobacco and pharmaceutical industries. The authors present 3 case studies. One shows how tobacco companies pressured pharmaceutical companies to scale back their smoking cessation educational materials that accompanied Nicorette. The second shows how they restricted to whom the pharmaceutical company could market its transdermal nicotine patch. In the third case, the authors show how subsidiary tobacco and pharmaceutical companies of a parent company collaborated in the production of a nicotine-release gum. The authors suggest that because tobacco cessation product marketing has been altered as a result of these financial conflicts, disclosure would serve the interest of public health.

References (abridged):

1. Markides CC. To diversify or not to diversify. Harvard Business Review. 1997;75:93-99

2. Krantz A. Diversification of the drug discovery process. Nat Biotechnol. 1998;16:1294

3. Blum A. Diversification in the tobacco industry. NY State J Med. 1985:328-334

4. Joossens L. Diversification is the future for many tobacco farmers. Tob Control. 1996;5:177-178

5. Landman A. Push or be punished: tobacco industry documents reveal aggression against businesses that discourage tobacco use. Tob Control. 2000;9:339-346

J. Am. Med. Assoc. http://www.jama.com

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