October 22, 2014

1. Guidelines for Minimizing the Effects of Conflicts of Interest in Genetic Research on AddictionThomas F. Babor and Katherine RobainaUniversity of ConnecticutSchool of Medicine October 22, 2014

2. Industry involvement in genetic research: tobacco • Council for Tobacco Research (CTR), the main tobacco-industry-funded research body, ran a $20 million a year research program which focused on genetics 1954 -1999 • CIR was among the largest sponsors of medical research in the United States and had given close to $225 million to around 1000 researchers. • Research was directed at identifying familial cancers, the role of genetic factors in cancer formation, and the identification of oncogenes responsible for causing lung cancer • Promoted the idea that a gene both leads people to smoke and predisposes them to cancer.

3. Industry involvement in genetic research: alcohol ABMRF Ernest Gallo Clinic and Research Center BoD: John Dr. Luca, President and CEO of the Wine Institute; Joseph Gallo, President and CEO of E. & J. Gallo Winery; and Mary Gallo, widow and member of the Gallo Winery Advisory Board Research designed to identify the genetic components of susceptibility to alcohol abuse and alcoholism • Analysis of funding portfolio (2008–2010) indicated that more than half of all grants (58%)were given for biomedical research, including genetics • None went to environmental or public health research

4. Institute for Research onPathological Gambling and Related Disorders at the Division on Addictions • Received more than $7 million from the NCRG from 1996–2009 • supported the idea that an addictive personality, rooted in genetics, puts a small number of people at risk • thematic analysis of 45 projects listed on the NCRG’s website found that neuroscience received 32% of its funding, behavioral sciences 51%, and mental illness 17%, with all research focused on the pathological gambler • None addressed the environmental contributions to gambling problems

5. Conflict of Interest A conflict of interest is a situation or relationship in which professional, personal, or financial considerations could be seen by a fair-minded person as potentially in conflict with independence of judgement (FARM 1997). A conflict may be personal, commercial, political, academic or financial • Personal conflicts include “pet” theories, validation of one’s own ideas, achieving publishable results, and gaining recognition for a discovery • “Financial” interests may include employment, research funding, stock or share ownership, payment for lectures or travel, consultancies, and company support for staff (COPE 2001) • Conflict of interest is not in itself wrongdoing (FARM 1997)

6. Definitions

7. Types of funding and COI • Directsupport to Universities for investigators’ salaries and center endowments; declared consulting fees, travel, other monetary awards • Apparent • Ernest Gallo Clinic and Research Center at the University of California) • Unapparent • Undeclared funding • Indirect support from “independent” research funding organizations (e.g., alcohol and tobacco companies set up organizations that give research grants to young investigators – • European Research Advisory Board (ERAB) • ABMRF)/ Foundation for Alcohol Research • National Center for Responsible Gaming (NCRG)

8. Sources of influence • Tobacco industry • Alcohol industry • Pharmaceutical industry • Gambling industry • Government agencies • Other funding bodies • Other interest groups • Our own biases

9. Overview: Effects of COI • Conflicts of interest (COIs) in science and medicine have come under increasing scrutiny in recent years. Failures to disclose COIs have become and a major embarrassment to publishers, editors, and professional societies. • A positive association between COIs and the outcomes of research has been documented in a substantial body of research covering a variety of fields • Virtually all of this research has focused on financial COIs, in part because these conflicts are more easy to report and to document.

10. ISAJE Annotated Bibliographies(www.isaje.net) • Research on competing interests in science, medicine and addiction studies (64 articles) • The Alcohol Industry and Competing Interests (38 articles) • The Gambling Industry and Competing Interests (10 articles) • The Tobacco Industry and Competing Interests (36 articles)

11. “Corporate Social Responsibility” Strategies of Addictive Consumption Industries • Increase the social and psychological availability of product • Improve public perceptions of the industry (e.g., responsible drinking”, gaming, etc.) • Narrow the focus to a small subset of the population (i.e., binge drinkers) and emphasize personal responsibility, while minimising industry responsibility • Highlight irresponsible users as the problem, rather than the product itself. • Exaggerate the health or recreational value of product.

12. Examples of strategies used by addictive consumption industries • Vulnerability of “special populations” to the adverse effects of alcohol consumption is “generally not psychological or due to social or economic conditions,” but is “instead, a biological predisposition [which] makes them especially susceptible.” –International Center for Alcohol Policies (ICAP) • “[Genetic research]…primarily a means of attracting researchers to areas of scientific inquiry not being addressed and, in particular, were focused on satisfying the needs of lawyers involved in defending the tobacco industry in litigation” –Legacy Tobacco Documents

13. Consequences of COI • Stigma • Dissention among colleagues • Research bias • Agenda setting by commercial interests • Bureaucratic regulation • Legitimacy for commercial interests

14. Research Bias • Impact of financial contributions and gifts is often unconscious • Self-interest asan automatic response and “viscerally compelling” • Deliberate fudging of data or interpretation of findings in order to maintain funding stream is rare but damages science when it occurs • Subtle bias motivated by norm of reciprocity

15. Research bias • Evidence supports the claim that industry-funded research produces industry-favourable results: • Alcohol (McCambridge & Hartwell 2014), • Pharmaceutical (Als-Nielson et al., 2003) • Tobacco (Wallace, 2009; Barnes and Bero, 1998)

16. Implications • Effect on clinical decision-making and public policy • Loss of credibility and trust in science • Impact on collegiality

17. Agenda Setting • To the extent that funding for a particular research question is dictated by commercial reasons, it is likely to alter the research agenda of the recipient organisation or an individual. • Industry funding for tobacco and alcohol has been criticised because it often supports topics that are considered favorable to an industry’s commercial interests (Babor, 2009).

18. How to minimize conflicts of interest (COI) Regulatory bans, Ethical analysis, total bans

19. Three Approaches to COI • 1) “Hands-on” approach • 2) “Hands-off” approach • 3) Moral jeopardy analysis linked to guidelines developed by expert committees

20. 1) “Hands-on Approach” • Engage in dialogue with industry representatives, set conditions for the acceptance of industry funding for programs and research, and participate as “partners” in industry-funded scientific activities, based on the assumption that the industry is acting as a “good corporate citizen” and will spend the money anyway. • Government cuts to funding for public health campaigns are a reason for partnerships with the industry.

21. Rationale for questioning hands-on approach • Industry motivated primarily by shareholders’ emphasis on bottom line • Industry representatives have no expertise in research and research priorities • Potential for research bias, agenda-setting, etc. • Precedents set by tobacco, pharmaceutical, alcohol and gambling industries • “Partnerships” tend to be one-way and one-sided, with industry have equal role in agenda-setting when researchers are not invited to set the industry’s agenda.

22. 2) A “hands-off” position • Investigators and organizations are advised not to engage in communication or collaboration with addictive consumption industry representatives. • Based on the assumption that the commercial interests are incompatible with the values and aims of health promotion, disease prevention and scientific research.

23. Clarion Declaration, 2008 • The alcohol industry is …involved in disseminating information, collecting industry statistics, research and development activities, legislative and regulatory lobbying, information and education programmes, media relations, marketing, and scientific research; and the development of social aspects organisations which are funded by the alcohol beverage industry to manage issues from the industry’s point of view ostensibly from a neutral position • The industry's research-related activities often question or compete with social policy or public health views about alcohol problems and related policy options, particularly the need for effective strategies to prevent alcohol problems. • Industry-supported research activities are used to enhance a false perception of corporate citizenship and thus gain political legitimacy for the industry. Industry involvement in research is therefore an efficient way for the industry to influence politics in ways that are favourable to the industry's commercial interests.

24. Clarion Declaration, 2008Conclusions • The twin aims of protecting the public from alcohol related harm and the alcohol industry’s mission to promote and sell as much alcohol as possible are inherently incompatible • Therefore to protect the integrity and legitimacy of alcohol research, and the reputation of academic institutions in the field of alcohol research, as well as public health no funding relationships with the alcohol industry should be entered into.

25. Limitations of hands-off approach • Funding sources differ in extent of moral jeopardy • Many researchers already accept funding • Opposition to control and independence

26. 3) Regulatory Guidelines COI declarations required by journal editors, professional associations, government agencies, and international organizations EXAMPLE: The World Health Organization and the Pan American Organization are currently developing guidelines for UN Member States to manage interactions, including research, between dangerous consumption industries (food, soda, alcohol, tobacco) and governmental health agencies. Moral jeopardy analysis linked to guidelines developed by expert committees

27. PERIL Analysis (Adams, 2007) • Purpose • Are the purposes of the funding and recipient organizations divergent or consistent? • Extent • To what extent does the recipient rely on this source of funding?   • As the proportion of income increases, it becomes more difficult to separate from the source’s expectations. • Relevant harm • What is the harm associated with the product or service provided by the organization?. • Identified • Does the funding organization benefit from being identified with the researcher’s reputation or organization?   • Is there a visible association with public good activities for the purposes of positive branding. Can this be used for political or commercial purposes. • Link • What is the Link between funder and researcher?  The more direct the link, the stronger the influence and the more visible the association.

28. Guidelines for individuals • Be informed about the risks associated with all funding sources • Support institutional policies regarding industry funding of research by dangerous consumption industries • Adopt a hands-off or moral jeopardy approach to industry funding • Declare all real, apparent or potential conflicts of interest to journal editors and other responsible sources. • Advocate for the creation of funding sources that are independent of commercial interests in the conduct of addiction research

29. Guidelines for organizations • Develop COI declaration procedures and ask all candidates for membership or election to a leadership position to provide information about financial and non-financial conflicts • Make COI declarations a condition for certifying scientific journals in the context of ethical standards • Develop policies for professional societies, non-governmental organizations, government agencies, and international organizations.

30. Primumnon nocere