The Blue Ridge Academic Health Group Managing Conflict of Interest in AHCs to Assure Healthy Industrial and Societal Relationships Report 10 September 2006 Mission: The Blue Ridge Academic Health Group seeks to take a societal view of health and health care needs and to identify recommendations for academic health centers (AHCs) to help create greater value for society. The Blue Ridge Group also recommends public policies to enable AHCs to accomplish these ends. Report 10 September 2006 The Blue Ridge Academic Health Group Managing Conflict of Interest in AHCs to Assure Healthy Industrial and Societal Relationships Members and participants Me m b e r s Bruce C. Vladeck, PhD, Interim President, Enriqueta C. Bond, PhD, President, University of Medicine and Dentistry of New Burroughs Wellcome Fund Jersey Darryl Kirch, President, Association of Steven A. Wartman, MD, PhD, President, American Medical Colleges Association of Academic Health Centers Catherine DeAngelis, MD, Editor in Chief, Journal of the American Medical Association Invited Participants Haile T. Debas, MD, Executive Director, Claudia Adkison, JD, PhD, Executive Associate Global Health Sciences Institute, Dean for Faculty Affairs, Emory University University of California, San Francisco Mark Barnes, JD, *Don E. Detmer, MD, President and CEO, Partner, Ropes and Gray American Medical Informatics Association; Joseph B. Martin, MD, PhD, Professor Emeritus and Professor of Medical Dean, Harvard Medical School Education, University of Virginia Per Peterson, MD, PhD, Chairman, Research Arthur Garson, Jr. MD, MPH, Vice President and Pharmacology, Johnson & Johnson and Dean, School of Medicine, University of Barbara S. Fox, PhD, Oxford Bioscience Partners Virginia Michael A. Geheb, MD, Division President, Oakwood Hospital & Medical Center/Heritage Staff Hospital Janet Waidner, Executive Administrative *Michael M.E. Johns, MD, Executive Vice Assistant, Woodruff Health Sciences Center, President for Health Affairs; CEO and Director, Emory University The Robert W. Woodruff Health Sciences Center, Emory University Editor Jeffrey Koplan, MD, MPH, Vice President for Jonathan Saxton, MA, JD, Academic Health Affairs, Emory University Special Assistant for Health Policy, Steven Lipstein, President and CEO, BJC Woodruff Health Sciences Center, HealthCare, St. Louis Emory University Arthur Rubenstein, MBBCH, Dean and Executive Vice President, University of Design Pennsylvania School of Medicine Peta Westmaas Design Inc. Fred Sanfilippo, MD, PhD, Vice President and Executive Dean for Health Sciences; Dean, College of Medicine; CEO, Ohio State University Medical Center John D. Stobo, MD, President, University of Texas Medical Branch at Galveston *Co-Chairs Contents Report 10: Managing Conflict of Interest (COI) in AHCs to Assure Healthy Industrial and Societal Relationships Executive Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Part I. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 COI: What is it? Why should we care? 6 Understanding the COI challenge 7 Part II. Findings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .8 Finding #1: COI matters a great deal to the public. 8 Finding #2: COI mostly occurs not as a “headliner” issue but rather in ways that are cumulative, less immediate, and more subtle—and perhaps even more damaging in the long run. 8 Finding #3: The academic, professional, and nonprofit sectors have been slow to address COI policy and implementation. 9 Finding #4: There is a lack of coordination or standardization of COI policies and implementa- tion/enforcement. 9 Finding #5: The academic/nonprofit/government sector has failed to be proactive in educating the public about the many relationships with the private sector and about the measures being taken to protect the integrity of bioscience and health care. 10 Part III. A Growing Pallet of Solutions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . 11 . Transparency and full disclosure 11 New strictures on gifts and remuneration 11 Independent and external oversight or separation methods 12 Special purpose entities 12 Zero financial interest tolerance 12 Part IV. At Stake: Global Health Security . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . .14 From a mine field to a field of dreams 15 Recommendations 17 Appendix 1. Harvard Medical School policy on conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Appendix 2. University of Pennsylvania School of Medicine COI policy for faculty . . . . . . . . . . . . . . 27 Appendix 3. Selected hypothetical examples of difficult conflicts of interest . . . . . . . . . . . . . . . . . . . . 32 Appendix 4. Federation of American Societies of Experimental Biology: Shared responsibility, indi- vidual integrity: scientists addressing conflicts of interest in biomedical research . . . . . . . . . . . . . . . . 33 Appendix 5. Association of American Medical Colleges: Principles for protecting integrity in the con- duct and reporting of clinical trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Reproductions of this document may be made with written permission of The Robert W. Woodruff Health Sciences Center by contacting Janet Waidner, Woodruff Health Sciences Center, Emory University, 1440 Clifton Road, Suite 400, Atlanta, GA 30322. Phone: 404-778-3500. Fax: 404-778-3100. E-mail: blueridge@emory.edu. Managing Conflict of Interest in AHCs to Assure Healthy Industrial and Societal Relationships is tenth in a series of reports produced by the Blue Ridge Academic Health Group. The recommendations and opinions expressed in this report represent those of the Blue Ridge Academic Health Group and are not official positions of Emory University. This report is not intended to be relied on as a substitute for specific legal and business advice. Copyright 2006 by Emory University. The Blue Ridge Academic Health Group Report 10 The Blue Ridge Academic Health Group (Blue Ridge Group) studies and reports on issues of fundamental importance to improving our health care system and enhancing the ability of the academic health center (AHC) to sustain optimal progress in health and health care through sound research—both basic and applied—and health professional education. In nine previous reports, the Blue Ridge Group has sought to provide guidance to AHCs that can enhance leadership and knowledge management capabilities; aid in the adoption and development of Internet-based capabilities; contribute to the development of a more rational, comprehensive, and affordable health care system; improve management, including financial performance; address the cultural and organizational barriers to professional, staff, and institutional success in a value-driven health system; improve the education of physi- cians and other health professionals, lead comprehensive health care reform; and revive med- ical professionalism (Blue Ridge Academic Health Group 1998a, 1998b, 2000a, 2000b, 2001a, 2001b, 2003, 2004, 2005). The Blue Ridge Group has been advocating for a “value-driven” health care system for nearly a decade. A healthy population is a paramount social good. A value-driven health system would manage both individual and population health and promote safety, quality, and efficiency. Through competition and rewards, providers, payers, states, communities and individuals alike would have incentives to achieve improvements in health. Universal and equitable access to evidence-based, effective care would help ensure that population health, information, and data management strategies can be implemented. A value-driven health system also would maintain the highest standards of professionalism and integrity in the pursuit of health and healing. For more information, visit our web site at www.blueridgegroup.org. The Blue Ridge Group has been advocating for a “value-driven” health care system for nearly a decade. A healthy population is a paramount social good. Executive Summary National Institutes of Health (NIH). These govern- In this, our 10th report, the Blue Ridge Group ment agencies would invest heavily in research at reviews the issue of conflict of interest (COI), par- universities and help sustain the strong ties between ticularly in the relationship between academic/non- academic science, industry, and the military that profit/government (ANG) health professionals and had been so successful in aiding the war effort. institutions and their partners and sponsors in the Yet, despite the ensuing large increase in discovery private sector. COI can compromise the integrity and the knowledge base, the process for translat- of research, education, care, and service. Even the ing discoveries and innovations into useful prod- appearance of COI can undermine the public’s trust ucts and services often was slow and inefficient. in and support for this vital work. Yet, the develop- Opportunities were lost. America’s intellectual ment and enforcement of COI policies at universi- property patent and laws were major impediments. ties and AHCs is still very much underdeveloped—a Among other problems, the laws held that the work in progress. To further this work, we describe federal government retained title to any discovery the emerging best approaches for managing COI made with government funds. This discouraged the and recommend action steps to improve COI policy private sector from developing ideas and technolo- and management. Additionally, to address gaps gies created in federally funded labs. and problem areas in COI law and regulation, we Bayh Dole marked the culmination of numerous recommend that the Institute of Medicine (IOM) efforts to reform U.S. patent law, enabling individu- become engaged to conduct a thorough review of als and institutions to claim title to any invention this issue and to recommend updated approaches, or innovation made while supported in whole or in which will further define COI issues in public/pri- part by government funds. And it explicitly encour- vate sector collaboration to meet national and aged academic institutions and other public sector global health goals. owners of such intellectual property to employ private sector partners to translate discoveries and innovations into new products and services. In an part I. economy increasingly based on the development Introduction and exploitation of knowledge, Bayh Dole asks Conflict of interest is an increasingly significant universities to be important engines of economic problem in the complex relationships between ANG development. sector health professionals and institutions and Bayh Dole opened many new pathways for tech- their private sector partners and sponsors. COI can nology transfer, but it did not provide a compre- compromise the integrity of research, education, hensive road map. In the intervening years, there health care, and service. Even the appearance of has been tremendous expansion, innovation, and COI can undermine the public’s trust in and sup- collaboration between the nonprofit and for-profit port for this vital work. For the sake of achieving sectors. Evidence shows real gains for technology optimal progress in advancing health and healing, transfer. However, both the non-profit and for-prof- ANG health professionals and institutions must bet- it sectors have experienced significant challenges in ter understand and manage COI. defining these relationships and in managing the In 1980, Congress passed the Bayh Dole Act resulting conflicts of interest. The challenge is to (Bayh Dole), marking a watershed in public pol- ensure the integrity of patient care, education, and icy designed to facilitate scientific collaboration basic and clinical research, especially in the drug between the public and private sectors (Bayh Dole and device development process. At stake is the 1980). A brief history explains why this even was public trust in AHCs and others in the ANG sector significant. In 1945, having overseen coordination that rely upon that trust in carrying-out their mis- of scientific efforts in the United States (which had sions. played critical roles in the Allied victory in World The Blue Ridge Group believes that university War II), Vannever Bush catalyzed the creation of AHCs and their administrators, researchers, and the National Science Foundation (NSF) and the health professionals have special obligations to protect the public interest by both maximizing industry is only the latest wrinkle in the challenge opportunities for technology transfer and by being of earning and maintaining public trust in the vigilant in ensuring the integrity of public/private integrity of research, training, and clinical care in sector relationships and their work products. the academic and nonprofit sectors. But it is a big wrinkle. Conflict of Interest: What is it? Bayh Dole opened a new and growing array Why should we care? of methods, influences, and situations through COI is best defined as “situations in which primary which secondary interests (including the primary and secondary interests coexist” (Thompson DF interests of for-profit enterprises) can impinge 1993). Such situations can exist for both individu- —or give the appearance of impinging—on the als and institutions. Primary interests within the integrity of academic, professional, nonprofit, and academic environment include facilitating higher governmental activities. While individuals and learning and the search for new knowledge and businesses in the for-profit sector may share many “truth” in the classical sense (AAUP 1954). Within of the goals, values, and missions of non-profits the AHC and the health professions, these are sup- or professionals, the rules and imperatives of sur- plemented by the primary interest of the patient, vival in the market place ultimately while seeking to help him or her, articulated in the impose profit-making as the pri- The public policy Hippocratic Oath: “First, do no Harm”. mary interest. Officers and direc- tors owe a fiduciary duty to the shift to enable Conflicts of interest matter for the AHC for two major reasons. First, they implicate the integrity company and to the shareholders greater collabora- of research and other activities associated with to produce a return on investment. tion with private the environment and conditions for “free inquiry,” ANG individuals and institutions industry is only within which scientists and others search for often fail to fully comprehend the the latest wrinkle knowledge and truth. The search for truth and the implications of their participation infrastructures that support it rely largely on the with the private sector, especially in the challenge public’s trust and popular willingness to support secondary interests that may con- of earning and such free inquiry with public funds. Second, COI flict with primary ANG interests maintaining is of special concern in the clinical research, health and responsibilities. public trust. care, and education environments. Human vulner- Research by Bekelman and ability in light of disease and injury creates a moral colleagues underscores just how imperative for the integrity of caregivers while the extensive are industry ties between reliance of students and trainees on their teachers the public and private sectors in research. and mentors creates a moral imperative for the Approximately one quarter of all U.S. investigators commitment of educators to the best interests of now have private industry ties, and roughly two their students. thirds of academic institutions hold equity in start- COI is not new in the academic or clinical envi- ups that sponsor research performed at the institu- ronments. Long-standing secondary interests and tions (Bekelman, et al. 2003). The financial rewards sources of conflicts requiring management within of industry collaboration can be significant. In academia and the nonprofit sector include hubris, university research alone, total private industry the desire for academic promotion, competition financial contributions now dwarf total public and for sponsored research support and “interesting private foundation support (Moses and Martin cases,” competition to be the first to publish dis- 2001). There is evidence of increasing private sec- coveries, an aspiration for a good reputation and tor support for both basic and clinical research and for higher pay and revenues, and competing com- of increasing returns to universities for their efforts mitments or outside interests. The public policy in patenting and licensing of discoveries and inno- shift to enable greater collaboration with private vations (E&Y 2000). Categories of Faculty Relationships with Industry Exhibit 1: that give rise to COI 1. esearch relationships: Support by industry, R mercializing university- or government-based usually through a grant or contract. research. 2. onsulting relationships: The compensated C 5. raining relationships: In these cases, T provision of advice or information, usually from industries provide support for the research or an individual academic or government scientist educational expenses of graduate students or or administrator, to a commercial organization. postdoctoral fellows, or contract with academic institutions to provide various educational 3. icensing relationships: The licensing of gov- L experiences (such as seminars or fellowships) to ernment- or university-owned technologies to industrial employees. industry, often negotiated and managed by an office of technology transfer located within the 6. ift relationships: Gift relationships are based G government, universities, medical schools, or on the transfer of scientific and nonscientific independent hospitals. resources, independent of an institutionally negotiated research grant or contract, from Equity relationships: The participation by 4. industry to academic or governmental scientists. academic or government scientists in the found- ing and/or ownership of new companies com- (Campbell, et al 2005) Understanding the COI Challenge from consulting or lecture fees to direct or indi- The challenges of identifying and managing rect support of an individual’s research or labora- COI in the academic environment are many. tory and/or other university interests. The entire ANG sector in the Bayh Dole era has All of these relationships can “make sense” in become increasingly entrepreneurial. Faculty in the context of a particular situation or transac- AHCs now are expected not just to pursue dis- tion. Yet each carries varying degrees of “sec- covery and innovation but also upon approach- ondary interest” implications that need to be ing or achieving such milestones to work imme- known—and in many cases managed. Some diately with the institution’s “technology transfer” must be prohibited outright. office to file patents and to seek licensees. Many Much has been written about COI in academia faculty become entrepreneurs themselves and and the nonprofit sector. The sholarly literature on start companies to exploit their own discoveries, the subject spans the fields of health policy, ethics, sometimes employing colleagues and/or stu- law, politics, business, and the professions. And a dents. Many serve in a variety of roles for private popular, journalistic literature—often based on sector companies, including as board members, examples, reports and exposes of poorly managed consultants, and advisers. These roles can range COI—covers these issues often in all the major from participation in basic research to product public and private journalistic and news media. Yet development, from sales and marketing to pro- development and enforcement of COI policies at fessional education. Many types of remuneration universities and AHCs is still very much underde- are employed in these relationships, from direct veloped—a work in progress. payments to grants of stock and stock options, part II. Q urveys S of representative published biomedical Findings research in a number of fields show significant For our purposes, several findings stand out in this statistical relationships between industry sponsor- literature. ship and positive research results (Bekelman, et al. 2003). Finding #1. COI matters a great deal to our public Q here are examples of clinical research studies T COI is a recurrent issue with a clear capacity for where researchers have failed to divulge relevant creating headlines of the type that most individuals industry sponsorship or ties and where reported and institutions would like to avoid. The capacity results have been more positive than would be for headline creation indicates a strong public inter- expected from a random sample (Bekelman, et al. est in the integrity of bioscience policy and practice. 2003). A single tainted study or a lone injured patient is Q rowing evidence indicates that even relatively G sufficient to elicit public notice and outrage. small or “token” gifts, such as some of those pro- In recent years, a number of such scandals as vided by pharmaceutical companies to doctors well as tragic incidents involving research subjects and trainees, act to influence the gift recipients have surfaced, raising important questions about and to stimulate attention to secondary inter- whether investigators and/or their institutions have ests. (Wazana 2000; Dana & Lowenstein 2003). sufficiently identified and mitigated potential or Q tudies and reports of COI reveal causes by the S actual secondary interests in the outcomes of the secondary interests of researchers and profes- studies (Altman LK 2006). Many of these incidents sionals acting as consultants for biotechnology, have occurred at some of our nation’s most pres- pharmaceutical, and financial sector companies tigious medical centers and universities, including (Topol & Blumenthal 2005). Harvard (Leary WE 1989), Johns Hopkins (Levine Q ew light is being shed on the increasing problem N J 1990), the University of Pennsylvania (Vogel G of institutional COI, where the institution has put 2000), and the Cleveland Clinic (Armstrong D itself in the position of having to manage mul- 2005). Scandal concerning COI also penetrated tiple and significant “secondary interests” that can recently to the heart of the conduct and sponsor- otherwise damage its integrity (Johns et al. 2003). ship of federal research at the NIH (Willman D Q Concern is growing about researchers and clini- 2003). And many of the most prestigious medical cians who serve as researchers and consultants to and biomedical research journals also have felt the financial and investment organizations where their effect of COI questions, including the New England advice or scientific judgment can result in signifi- Journal of Medicine (NEJM) (Goozner 2004) and cant, if unintended and unforeseen, COI issues the Journal of the American Medical Association (Bekelman, et al. 2003). (JAMA) (Armstrong D 2006). These examples are just a few of the better-known In addition to this growing body of evidence COI cases. COI revelations and scandals continue concerning ties to the private sector, widespread to strain and damage the public’s trust in academic concern is spreading within academia about how and nonprofit research and clinical care. We can private sector relationships are exacerbating related and need to do better. faculty and staff conflicts, including conflicts with respect to: Finding #2. COI mostly occurs not as a “headliner” Q ommitment and service to home institutions c issue, but in ways that are cumulative, less imme- —e.g., where time involved in private sector diate, more subtle, and perhaps in the longer term relationships conflicts with the commitments even more damaging. required to the institution; More and more is becoming known about the Q entoring and training of students—e.g., where m mechanisms and effects of “secondary interests” students are directed to work for, or on projects for academic and other nonprofit-based individuals of interest to, a faculty member’s new start-up and institutions. company. Q cademic a freedom—e.g., where faculty might employed researchers but only after the Los agree with a private sector sponsor to delay Angeles Times ran a series of articles alleging publication or refuse to share research results improper financial ties between NIH researchers with colleagues and the larger research com- and industry partners (Willman 2003). munity (Blumenthal 2003; Boyd and Bero Equally important, research also shows that 2000). almost no information is available on how or how While the financial ties and conflicts with exter- well COI policies are implemented or enforced nal partners may create the most potential for within universities, professional societies, or the headlines in the popular press that undermine the rest of the nonprofit sector (Boyd et al. 2004). public’s trust, other forms of secondary interest Others are equally convinced that there is a clear and conflict also can have a significant effect on obligation on the part of the research community the integrity of the academy and the missions of to be proactive in ensuring that results from stud- the ANGs. ies involving human subjects are reported so that anyone can learn the results (Sim and Detmer Finding #3. Academic, professional, and nonprofit 2005). sectors have been slow to address COI policy and implementation. Finding #4. There is a lack of coordination or Universities that receive federal funds are standardization of COI policies, procedures, required to establish policies that prevent faculty, implementation, and enforcement across the staff, trainees, and board members from using ANG sector. their positions for private financial gain for them- Most AHCs, professional associations, and selves and their families. The policies also prohibit organizations have developed COI policies (e.g., financial interests in vendors, gifts, gratuities and AAMC 2001, 2002; AMA 2001; ASGT 2002). The favors, nepotism, research, training, and other Uniform Requirements for Manuscripts adopted areas such as political participation and bribery. by the International Committee of Medical Journal These requirements cover more than research con- Editors (ICMJE) requires disclosure to all sub- flicts. (McCrary et al. 2000) jects and to journals of all COIs (ICMJE 2003). However, surveys of academic institutions show The pharmaceutical industry has developed a that a wide variation in the development, content, comprehensive policy concerning COI (PhRMA and enforcement of COI policies. Whereas some 2004). The Federation of American Societies of institutions have developed extensive policies and Experimental Biology (FASEB) has adopted a attendant processes for implementing them, oth- “consensus statement on overarching principles ers have hardly addressed these issues at all. Cho and voluntary standards for the conduct and et al. and McCrary et al. surveyed university COI management of academia/industry interactions policies and found significant variation and gaps from the scientists’ perspective” (FASEB 2005, vi). in COI policy and implementation. The typical The Association of American Medical Colleges institution requires disclosure of faculty financial (AAMC) has adopted “Principles for Protecting interests only annually and fewer than one-fifth Integrity In the Conduct and Reporting Of specified limits or prohibitions on faculty activities Clinical Trials” (Ehringhaus and Korn 2006; see (Cho et al. 2000:2207). In another study, only 1% Appendix 5). of 250 institutions surveyed had policies requiring Yet while some in the AHC community have the disclosure of potential COI information to the called for the adoption of uniform standards relevant institutional review boards (IRBs) or to (Korn 2000; Cho et al. 2000; Campbell, et al. 2005; research subjects (McCrary et al. 2000:1621). The Brennan et al. 2006), “each boat on its own bot- same variation and gaps exist in policies promul- tom” seems to be the overriding philosophy of gated by professional societies (Ibid). leadership in the AHC community. As a result, In the government sector, the NIH recently little sharing of common standards, policies, or conducted a careful review of COI policies for enforcement mechanisms has taken place either within or between universities until recently. And tive in educating its public about its many rela- few organizational and technological resources are tionships with the private sector and about the available to support the promulgation of standards, measures being taken to protect the integrity of data reporting, or monitoring (Boyd et al. 2004). bioscience and health care. Experience shared within the Blue Ridge Group Much of the public and the press only encounter suggests that variation in the culture and manage- COI issues when something goes wrong. The pubic ment of particular AHCs precludes standardization policy imperative to explore this new ground, take of policy and practice in COI management. At the some risks, and develop these relationships is not same time, these myriad separate guidelines, princi- understood. Instead, the public repeatedly finds ples, strictures, and policies —and also their uncer- reason to be skeptical of the capability and commit- tain enforcement—are acknowledged to be sources ment of many in the ANG sector to their primary of risk to institutions and individuals. interests in the face of apparent secondary interests, Schools of medicine at both Harvard and the especially the potential pecuniary rewards of rela- University of Pennsylvania have developed and tionships with the private sector. amended model COI policies over time (see appen- One important implication of these findings is dices 1 and 2). Both of these institutions’ policies that the public trust necessary for sustaining sup- are comprehensive. They cover similar ground port of ANG research and care activities is at risk. and espouse similar principles. Yet, an expectation While there has been sustained support of the NIH remains that each institution will evolve its own budget over many years along with a recent dou- implementation, enforcement, and practices—its bling of this investment, this support was won only own COI culture. As stated in the Harvard policy, after significant efforts. It cannot be taken for grant- “it is expected that a common institutional expe- ed. Most importantly, in the post 9/11 environment, rience in the application of these guidelines will strong competition for public resources to address gradually evolve” (appendix 1). Nevertheless, these national security. Regardless, support for basic and two institutions’ policies are very good models for clinical research funding can erode further. others to use in developing institutional COI poli- The COI issue has had one additional signifi- cies, and we recommend them. cant effect. The lack of proactive attention to COI Finding #5. The ANG sector has failed to be proac- issues has led to a broad spectrum of regulatory For our Public and our Patients Martin and Kasper have suggested that, Q t o be confident that participation in because medicine addresses a basic human the development of new therapies will need, institutions, professionals, and others be safe, with fully informed consent involved in the public, nonprofit sector of obtained at the outset and access to out- health care and research owe their public come data provided during follow-up. the following: Q o know about any potential adverse t effects that might influence their consent Q t o know that the biomedical research to participate in the research. they support will be a search for truth, Q o be assured that neither the decision t uncontaminated by even a perception of to ask patients to participate in a clini- bias. cal trial nor the assessment of the risks Q o see that discoveries with the potential t patients may incur will be prejudiced by to improve health are rapidly translated an investigator’s personal profit motives. into practice through clinical trials. (Martin and Kasper 2000) 10 guidelines and legal enforcement that has steadily New Strictures on Gifts and Remuneration “annexed terrain previously controlled by profes- Brennan et al. have suggested a series of simple sional ethics” (Studdert et al, 2004). This effect is but strong measures to limit the effects of some deeply troubling. The continuing erosion of the common health industry practices currently prac- sphere of professional self-regulation and auton- ticed at some academic health centers. Ample omy undermines medical professionalism itself. It evidence exists that all of these practices can and threatens the social legitimacy and authority that do implicate secondary interests, which affect both is critical to the future of the profession and its physician and trainee behavior and expectations. capacity to guide public policy. The importance of Among the recommendations are: understanding and addressing the erosion of pro- Q prohibition on “all gifts ($0 limit), free meals, a fessionalism was the focus of the last Blue Ridge payment for time for travel to or time at meet- Group Report (BRG 2005). ings, and payment for participation in online Appendix 3 provides hypothetical examples of CME from drug and medical device companies COIs that are becoming more and more prevalent to physicians . . .,” within academic health centers and their medical Q prohibition of all pharmaceutical samples to a schools. Such complex COIs tax the capabilities of physicians to be replaced by a system of vouch- even those institutions with relatively comprehen- ers or similar arrangements for low-income sive COI management commitments (Ehringhaus patients, & Korn (AAMC) 2004). Q the exclusion from hospital and medical group formulary and formulary oversight committees part III. of anyone with a financial relationship with a A Growing Pallet of Solutions drug manufacturer; a prohibition of direct (and A pallet of approaches to managing COI is grow- much indirect) industry support for CME pro- ing within the ANG sector, approaches that should grams and for physician travel, to be replaced by be adopted and further developed. In summary, contributions to university-controlled central they are: funding repositories with open reporting on the uses of such funds, Transparency and Full Disclosure Q prohibition of faculty serving on industry a Almost universally, academic and professional speakers’ bureaus or in other journals, societies, and granting agencies are capacities where the primary The best COI advocating the principles of transparency and full function is purely the market- policy will fail disclosure of industry ties (AAMC 2004, 2006, ing of products, Q prohibition on faculty pub- a if disclosures AMA, NEJM, ASGT 2000). Transparency involves full and timely disclosure of all actual or apparent lishing articles or editorials are not made, secondary interests resulting from private sector or that are “ghost written” by are inaccurate, or other relevant relationships. This element is funda- industry employees, and are insufficiently mental to COI policy. The best COI policy will fail Q new transparency for con- a complete. if disclosures are not made, are inaccurate, or are sulting and research con- insufficiently complete. However, many analysts tracts, including public post- understand that full disclosure by itself often is ing of the terms, along with the requirement insufficient, especially to a lay public or to patients, that such contracts provide for specific deliver- who may be ill-equipped to evaluate the nature ables. Also recommended is that AHCs create or potential impact of such secondary interests. an institutional mechanism to manage industri- Further action is indicated, ensuring that disclo- ally-based funding and fees rather than leaving sure is meaningful to a broad array of the public to this process directly in faculty hands (Brennan whom we are responsible (Weinfurt et al. 2006). et al, 2006). 11 Many of these recommendations would alter or Special Purpose Entities prohibit policies and practices that are routine in Related to the separation method, another impor- most AHCs and are unlikely to stop without insti- tant method for COI management is establishment tutional action. Where once these practices might of “special purpose” institutional entities dedi- be dismissed as insignificant, in the Bayh Dole era, cated to the management of COI. These groups arguably they have become more relevant as COI can include research institutes that a university challenges have expanded dramatically. Industry might create with private or industrial partners. believes that these practices do effectively influ- Prominent examples include the Howard Hughes ence faculty, staff, students, trainees, and even the Medical Institutes’ laboratories at various sites institutions overall. The adoption, with some local and the Whitehead Institute at the Massachusetts adjustments, of the Brennan et al. recommenda- Institute of Technology (Moses and Martin 2001; tions deserves open and active discussion and con- see www.hhmi.org/ Accessed August 10, 2006). sideration. Ohio State University Medical Center (OSUMC) offers another example. OSUMC has developed a Independent and External Oversight nonprofit public benefit corporation called UMC or Separation Methods Partners through which venture investments, start- In some areas of COI, conflicts and secondary up companies, and partnerships with the private interests are unable to be adequately or appropri- sector are structured and managed (see www. ately managed by employees or other individuals umcpartners.org/ Accessed August 10, 2006). with close ties to the parties Another approach is establishment of entities Members of institu- or interests that constitute the that can hold equity and receive royalties on behalf tional review boards COI. This scenario is especial- of faculty, other university employees, or the insti- (IRBs) who review ly true where the institutions tution itself (Moses and Martin 2001). All decisions and oversee stud- themselves have conflicts. For about management and disposal of investments instance, a university may and assets are made by this entity’s independent ies involving human hold licensing agreements financial advisers or board. The entity operates in subjects are never with or own an equity stake a manner similar to a mutual fund, and it may be allowed to profit in one or more start-up bio- structured similarly to those used in clinical prac- from their connection technology, pharmaceutical, tice foundations, common in AHCs (Ibid). with the review. Both or medical supply company, In all of these cases, relationships with the private and the university has need sector are cloistered into dedicated, separate entities law and policy now of a vendor in one of these where COI can be more systematically managed. prohibit IRB mem- areas. In cases like this, where bers from having any the institution itself may have Zero Financial Interest Tolerance financial interest in a conflict, strong arguments Certain positions and situations require a zero- exist for establishing indepen- tolerance financial interest policy for individu- the research they dent review panels (IRPs) con- als. For example, members of IRBs who review review. sisting of nonaffiliated people, and oversee studies involving human subjects are who have the expertise and experience to evaluate never allowed to profit from their connection with and manage real and potential conflicts (Barnes et the review. Both law and policy now prohibit IRB al., 2003; Johns et al. 2003). Additionally, institu- members from having any financial interest in the tions can manage institutional conflicts through research that they review. Johns et al. have called “separation methods,” separating the decision- for a policy that applies to all institutional deci- making in regard to investments from the flow of sions-makers and prohibits financial interests in information from clinical, research purchasing, or research being conducted at the institution (Johns other relevant operations—therefore, one is unable et al. 2003). to influence the other (Johns et al. 2003). 12 AHCs are urged to discuss and subsequently ment of a significant group dedicated to sharing adopt these procedures if transparent discussion at and developing COI policy among AHCs. The the institutional level shows a need for such action. Forum on Conflict of Interest in Academe (FOCI The Blue Ridge Group believes that AHCs must Academe) is a fast-growing organization of lead- devote new and significantly more resources to get- ers within medical schools and AHCs involved in ting control of and managing COI. Each AHC and COI review, management, and policy development. AHCs collectively should consider this entire port- FOCI Academe is dedicated to providing a forum folio of COI management options and strategies for leaders in biosciences and health care to under- and develop a coherent strategy for addressing this stand, develop, and promote the highest levels of challenge. The results of these deliberations should ethical and professional standards and is now affili- be shared with the public. ated with the AAMC (see www.forummeeting.com/ A positive recent development is the establish- Accessed August 2, 2006). Exhibit 1: The Forum on Conflict of Interest in Academe (FOCI Academe) Purpose The purpose of the organization is to provide a forum for leadership in the biomedical arena for those who oversee and manage conflicts of interest to promote the highest ethical and professional standards in the conduct of their institutions as they carry out their missions of patient care, research, education, business, and service. The organization will address the following at the institutional and national level: A. The development and review of policies on COI; B. Consistent best practices in the implementation of these policies; C.Productive academic/industry relationships that benefit the institutions and thereby the public without undue influence of the relationships upon the integrity of decisions made by the institutions; D. Education of the institutional faculty and employees, trainees, and officials and the enhancement of institutional cultures that promote ethical and professional behavior in institutional and personal relationships with industry; and E. Education of the media and the public on COI issues. Through its discussion of and engagement in these focus areas and others, the organization will enhance public confidence and trust in the institutional oversight of conflict of interest matters. --From the Bylaws of FOCI Academe FOCI Academe not only addresses particular environment and a road map for ANG collabora- conflict of interest issues as they arise but also tion with the private sector. it proactively creates a better policy and regulatory 13 part IV. global health threats. As Thomas Freedman has At Stake: Global Health Security noted, the world is essentially flat again (Friedman Extensive and increasing ANG collaboration with 2005). Because of the mobility of people worldwide, the private sector is now integral to almost the localized disease outbreaks can quickly become entire spectrum of biomedical and clinical research global outbreaks. HIV/AIDS, SARS, drug-resistant and health care, and therefore, to medical prog- TB, pandemic “bird flu,” and many other threats, ress. Conflicts of interest in relationships between both natural and man-made, show evidence that ANG and private industry are inevitable and will health security is a paramount issue. Even popu- continue. ANG individuals and institutions must lation health threats that develop more slowly, take aggressive steps to understand, anticipate, and such as the current epidemic of obesity and dia- manage these conflicts. However, since the pas- betes, require unprecedented resources and new sage of Bayh Dole, legal, professional, regulatory, approaches. and administrative activity and policy have taken Experience to date suggests that we are only primarily defensive and reactive stances. As ANG minimally prepared locally, nationally, and interna- and industry sectors explore and forge relation- tionally to confront, prevent, or manage health in ships, “rear-guard” actions that defend and enforce the age of globalization. Public health organizations traditional academic, professional, and organiza- and agencies worldwide are increasingly identifying tional values and ethics are unfolding. While this risks and promoting proactive policies and inter- “defensive” focus is absolutely vital to the integrity ventions. Yet public policy in general, and AHCs of the professions and to public trust in nonprofits, and the medical professions in particular, appears the ANG sector must develop a far more proactive to be insufficiently engaged in understanding and approach. Collaboration with the private sector planning for the levels of resources, capabilities, is likely to become even more extensive and more technological sophistication, and public/private important to the future of health and health care cooperation that may be required to meet foresee- (Emanuel, et al. 1999). able health challenges. The multiple and burgeoning relationships Health security as well as first-rate biomedi- between the ANG and private sectors are producing cal research in its own right—local, national, and unprecedented technologic progress and promise international—requires world-class and worldwide vastly many more. Scientists and clinical investiga- knowledge generation, discovery, innovation, and tors now talk with increasing confidence and cer- entrepreneurialism. Additionally, our global health tainty about the likelihood of new breakthroughs challenges also requires the capital, manufacturing, based on recent rapid advances in genomics, and marketing capabilities of industry as well as the proteomics, nanotechnologies, computational and authority and logistical and budgetary support of systems biology, and a host of other fields of dis- governments worldwide. covery that industry collaboration has accelerated. Above all, achieving the appropriate levels of Similarly, new drugs and devices, ranging from resources and capabilities for our global health chal- cancer therapeutics to drug-infused stents, from lenges requires an extraordinary commitment and remote telemedicine capabilities to robotics and effort on the part of the health professions, espe- extraordinary new developments in imaging and cially the medical profession. Strong and organized nuclear medicine, all reflect the rapid uptake in the leadership in medicine and the other health profes- marketplace of discoveries and innovations. sions is indispensable in defining and marshalling Importantly, both the health care marketplace necessary public and private resources. This process and the discovery and development process are includes explaining the realities of our “flat” world global in scope. Certainly the pharmaceutical to both policymakers and the public and advocat- industry is multinational as are clinical trials. But ing for the resources necessary to health security, globalization means more than just new opportu- including preparedness and intervention. nities. It also introduces new and unprecedented In this context, leadership is critical. The arena 14 of public policy has many competing claims for applications, providing for disclosure of con- allocation of resources. To be treated not simply as flicts by investigators—but not explicitly for the another “special interest,” ANG medical and health management or elimination of conflicts (see professional leadership must bring an unimpeach- www.hhs.gov/ohrp/humansubjects/finreltn/ able integrity, commitment, and track record to finalguid.pdf. Accessed August 8, 2006). marshal necessary resources, capabilities, and com- a. The Public Health Service (PHS) regulations mitments. Important to this challenge is the robust require every investigator to report on any engagement of such leaders in defining and cham- significant financial interests that may rea- pioning appropriate public/private sector relations. sonably appear to be effected by the research before application for funds is submitted From a Mine Field to a Field of Dreams to PHS, including NIH and CDC (DHHS The Bayh Dole Act enabled a broad advance of the 2005). forces of public and private sector collaboration. 5.The False Claims Act, which imposes liability Yet, for more than 20 years, these forces have had for knowingly submitting a false claim for to advance through a difficult minefield, painstak- payment to the federal government, is being ingly and not without significant casualties. It is employed increasingly to prosecute Medicare time to move public policy towards a more friendly and Medicaid fraud (31 U.S.C. §§ 3729-3733 terrain. By drawing on the lessons learned to date, (2004); see Krause JH 2002). the realities of our current environment, and our 6.The NSF has regulations similar to the PHS, projected health care challenges, we should aspire which require entities with more than 50 to create more of a “field of dreams:” a regulatory employees and that receive NSF funds to report and standards-based playing field to which ANG to NSF only COIs that CANNOT be managed and industry will more naturally be drawn for (NSF 2005). appropriate and necessary collaboration. 7.IRB members and process: FDA and PHS regu- Current laws have developed in specific areas of lations provide that no review by an IRB mem- interest and provide a foundation for broad-based ber is allowed of a study in which the member COI regulation and guidance. has a conflicting interest. However, “conflicting interest” is not defined but has been inter- 1.Internal Revenue Service (IRS) and state not- preted as being broader than financial interests for-profit law provides regulations concerning (Barnes M 2005). private inurement, while intermediate sanctions 8. Institutional Animal Care and Use No rules prevent self-dealing by non-profit board Committee (IACUC) member can participate members and executives (see, e.g., www.irs. in review in which member has conflicting gov/charities/charitable/article/0,,id=123298,00. interest (see www.iacuc.org/ and http://grants. html). nih.gov/grants/olaw/olaw.htm Accessed August 2.Federal and state anti-kickback law “curtails 10, 2006). corrupting influences of money on health care 9.Common law cases on COI. There is a growing decisions” (42 U.S.C. § 1320-7a (2004)). body of case law on COI. For example, Moore 3.The so-called “Stark” laws regulate physician v Regents of U California held that “a physician referrals (See: Omnibus Budget Reconciliation who is seeking a patient’s consent for a medical Act of 1989 (P.L. 101-239); Omnibus Budget procedure must, in order to satisfy his fiduciary Reconciliation Act of 1993 (P.L. 103-66); Social duty and to obtain the patient’s informed con- Security Act Amendments of 1994 (P.L. 103- sent, disclose personal interests unrelated to the 432)). patient’s health, whether research or economic, 4.Food and Drug Administration (FDA) regula- that may affect his medical judgment.” (793 tions address objectivity in research and the P.2d 479 (Cal. 1990)) see www.richmond.edu/ soundness of data submitted to support FDA ~wolf/moore.htm. Accessed August 9, 2006). 15 10. he pharmaceutical industry has adopted a T undefined and uncharted in most COIs (Barnes “code on interactions with health care profes- 2005). sionals.” Although voluntary, the code represents COI law and regulation are a complex patchwork an industry-wide standard that reflects current of standards and initiatives that remain ill-defined standards in law and regulation to which the and unfinished and that suffer from significant vast majority of the pharmaceutical industry gaps. As a result, many unsuspecting or unprepared subscribe (PhRMA 2004). individuals and institutions continue to face legal and ethical exposure as they seek to understand and However, substantial gaps exist in the current manage primary and secondary conflicts of inter- regulatory environment for COI in public/private est. Also at risk are the people they serve, including relationships. They include: patients, students, and the public at large. Most 1. OI policies of AHCs often fail to directly C troubling, perhaps, is that no entity or authority is address Stark and anti-kickback law issues. empowered to either chart or implement an overall These laws and regulations apply far beyond the strategy to create more comprehensive and univer- research context. sal standards. 2. on-financial COIs most often fail to be N Despite the reluctance of some to countenance addressed. more global standardization of COI policies, the 3. ather than direct regulation of institutional R Blue Ridge Group believes that such an effort is at COIs, only indirect applications of IRS and state least worth thorough investigation. In our global not-for-profit laws are applied to prevent deal- era, an overarching public interest in national ing in the assets of a nonprofit for the benefit of and global health security is present. To contrib- either insiders or for nonprofit purposes. ute appropriately to this interest, we should come 4. f research is neither used for an application to I together on these issues. Our collective solutions the FDA nor funded by PHS or NSF, no federal will be much better than if an individual ANG enti- rules apply at all on COIs of investigators. ty or each private company pursues only its own 5. RB and IACUC rules are limited. They forbid all I policies and interests concerning COI. National conflicts including those beyond financial con- and global challenges require more systematic and flicts, but the extent of forbidden conflicts fails to coordinated establishment and implementation of be defined. needed policies. 6. emedies, limits, and management strategies are R Most troubling, perhaps, is that no entity or authority is empowered to either chart or implement an overall strategy to create more comprehensive and universal standards. 16 Recommendations: 1. The Blue Ridge Group believes that AHCs must devote new and significantly more resources to getting control of and managing COI within their institutions and their extended family of fac- ulty, staff, and other interested parties. The effective management of COI requires the establishm- net of an institutional culture that starts at the top and works its way through the entire fabric of the institution. Each AHC should consider the entire pallet of COI management options and strat- egies and develop a coherent strategy for addressing this challenge. Sufficient resources must be allocated for management and enforcement of COI, including designated managers and account- ability systems. 2. The Blue Ridge Group recommends that AHCs and other relevant ANG organizations should sup- port the goal of creating, where possible, a common set of standards and practices for managing COI in ANG/industry relationships. Participation in FOCI Academe) is highly recommended as a forum and vehicle for leaders in biosciences and health care to understand, develop, and promote the highest levels of ethical and professional standards. The affiliation of FOCI Academe with the AAMC should greatly enhance this effort’s visibility, reach, and influence (see www.forummeet- ing.com/ Accessed August 2, 2006). 3. The Blue Ridge Group recommends that the Institute of Medicine (IOM) take charge of a review of the current laws, regulations, and relationships between the public and private sectors in tech- nology transfer. The IOM should make recommendations concerning appropriate policies or direc- tions for further policy development, filling current gaps in regulation. This policy could produce more sophisticated and appropriate legal and regulatory frameworks, within which public/private collaborations and relations can be ideally developed. 4. Such public policy guidance must have the input of all stakeholders in the nonprofit, govern- ment, and private sectors. To begin to create the groundwork for more consistent international approaches, laws such as those applying to the European Union and other parts of the world should be examined. The IOM should work with other academies around the world to evaluate, create, and pursue common ground. 5. Leading health and professional organization in the United States, including the AAMC, AAHC, AMA, and equivalent organizations in the other health professions, should review their own approaches to this topic at the local, national, and global level and prepare to offer leadership in developing and implementing revised and enhanced COI policies. Conclusion The challenges of managing COI are significant and require all stakeholders to understand not only the risks to individuals and institutions of failure to adequately address COI but also the risk to the progress of health care. Furthermore, failure to address COI and engage these issue proactively sets us on a collision course with the overarching public interest in national and global health. 17 Appendix 1 AVAILABLE AT: www.hms.harvard.edu/integrity/conf.html. ACCESSED AUGUST 9, 2006. HARVARD MEDICAL SCHOOL POLICY ON CONFLICTS OF INTEREST AND COMMITMENT Introduction 1. that the vast majority of scientists are honest and An important goal of the Harvard Faculty of Medicine conduct their research with the highest standards and is to make scientific discoveries that will benefit the sick integrity, and, and suffering. For many years the Faculty has worked 2. that, for the vast majority of cases, self-regulating hard to achieve this goal. In 1980, the United States structures and processes in science are effective. Congress explicitly sanctioned and facilitated this process with the passage of legislation designed to stimulate the Based on these assumptions, the Faculty of Medicine commercialization of faculty inventions by permitting believes that with clear guidelines and principles, in academic institutions and scientists to benefit financially conjunction with appropriate mechanisms for supervi- if their federally-sponsored research led to commercial sion and monitoring, cooperation between industry and products. Moreover, during the past decade the rate of academic medicine is consistent with the highest tradi- growth of biomedical research has outpaced federal fund- tions of the medical profession and can energize scientific ing, compelling universities and hospitals to develop alter- creativity. native sources of revenue to support the expenses associ- This policy is intended to serve as a guide for faculty ated with their educational, research and clinical missions. members in structuring their relationships with industry In response to these influences, biomedical research and other outside ventures in view of their academic institutions have cultivated a growing variety of relation- responsibilities for teaching, research and patient care. ships with industry which promise to benefit the public as Faculty members are expected to make reasonable inquiry well as the institutions themselves, their faculty and staff, as to whether their relationships and activities fall within and their industrial partners. Over the last several years, the provisions of the policy. It is not the intent of this these relationships have grown substantially, bringing new policy to regulate or eliminate all situations of conflict resources to the support of science and facilitating the of interest, but rather to enable faculty members to rec- translation of knowledge from the laboratory to the bed- ognize situations that may be subject to question and side. The Harvard Faculty of Medicine remains strongly ensure that such situations are properly reviewed and, if committed to continued growth in these innovative and necessary, resolved as applicable. Thus, an integral part mutually beneficial relationships. of the policy is a disclosure mechanism whereby faculty Together with these benefits, the growing partnership members regularly review their activities. The guidelines between for-profit enterprises and the University has are intended to maintain the professional autonomy of created new possibilities for conflicts of interest. These scientists and physicians inherent in the self-regulation conflicts arise from a faculty member’s opportunities to of science. These guidelines should be viewed as comple- benefit financially either from the outcome of his/her menting and elaborating upon the Faculty of Medicine’s research or from the legitimate activities conducted in the Statement on Research Sponsored by Industry.(1) course of his/her responsibilities as a faculty member. In The policy fulfills two other purposes as well. First, light of these possibilities, there is emerging public con- it provides faculty members with meaningful guidance cern regarding the appropriateness of some relationships for the continued development and future structuring of between academic medicine and industry. productive relationships with industry. Second, by virtue Public trust in the enterprise of academic medicine of its explicit nature and provision for full disclosure, the and the legitimacy of its powerful role in society require policy will provide assurance to the faculty, the University, a constant amenability to public scrutiny. Consequently, and most importantly the public, that such relationships it is necessary at this time to ensure the continued con- have been examined and will be conducted in a man- fidence of the public in the judgment of researchers and ner consistent with institutional and public values. It is clinicians and in the dedication of academic research expected that these relationships will allow the University institutions to the integrity of the scientific enterprise. and its affiliated Hospitals to pursue energetically new The strength of this assurance is based on two assump- knowledge in the biomedical sciences and to insure that tions underlying the explicit rules and implicit norms the transfer of such knowledge to the care of patients is governing faculty behavior at the Harvard Medical rapid and cost-effective. School: 18 Types of conflict Another classification (Category III) consists of instances Conflicts of Commitment that will ordinarily be permissible following disclosure With the acceptance of a full-time appointment in the and, where necessary, the implementation of oversight Faculty of Medicine, an individual makes a commitment procedures designed to ensure academic standards, intel- to the University (and Hospital, if part of a hospital- lectual values, and institutional integrity. Lastly, there is a based department or other health-care institution) (2) category of relationships (Category IV) that are thought that is understood to be full-time in the most inclusive to be allowable because they are (a) accepted practices sense. Full-time members of the Faculty of Medicine are and (b) generally minimal in their personal financial expected to devote their primary professional loyalty, impact. time, and energy to their teaching, research, administra- These classifications are not intended to serve as a tive responsibilities and, where applicable, patient care at rigid or comprehensive code of conduct or to define the School and its affiliated Hospitals. Accordingly, they “black letter” rules with respect to conflict of interest. It is should arrange outside activities and financial interests expected that the guidelines will be applied in accordance so as not to interfere with the primacy of these com- with the spirit of the mission of Harvard Medical School mitments. The Faculty of Medicine recognizes that its in education, research and patient care. By this process, it members may engage in outside professional work, and to is expected that a common institutional experience in the the extent these activities serve the Faculty’s interests, as application of these guidelines will gradually evolve. The well as those of the participant, the Faculty of Medicine complexity of the subject matter is such that the current approves of such involvement. However, no more than guidelines and their ensuing interpretations should be twenty percent (20%) of a full-time faculty member’s formally reviewed on a periodic basis. total professional effort may be directed to outside work, The impact of a Faculty Member’s conflict of inter- not to exceed the equivalent of one working day per week. est on student training (including that of post-doctoral Potential conflicts of commitment must be disclosed and fellows and other trainees) is of special concern to the resolved as described in the section on implementation in Faculty of Medicine. Many of the specific issues related Appendix B. to student training have already been addressed in the Members of the Faculty whose appointments are less Faculty of Medicine’s Statement on Research Sponsored than full-time are expected to devote professional loyalty, by Industry. As noted in that policy, students and train- time, and energy to their teaching, research, patient care, ees “should not ordinarily participate in research that and administrative activities, in accordance with their involves confidential information or otherwise con- agreed-upon time commitments. strains their right to publish or communicate freely.” Additionally, as set forth in more detail below, the Faculty Conflicts of Interest is particularly concerned about the content and quality A Faculty Member (3) is considered to have a conflict of the training experience for students whose research is of interest when he/she, any of his/her Family, or any sponsored by a for-profit business and whose preceptors Associated Entity possesses a Financial Interest in an have a personal interest in that business. activity which involves his/her responsibilities as a mem- It is essential that Faculty Members demonstrate at ber of the Faculty of Medicine. Included in these respon- all times their commitment to the highest intellectual sibilities are all activities in which the Faculty Member and ethical standards in all aspects of research, particu- is engaged in the areas of teaching, research, patient care larly research in which opportunities for conflict may and administration. exist. As a corollary, the training experiences of students are expected to incorporate the values of objectivity in Guidelines for conflict of interest research and the importance of public trust. The following is a representative and non-inclusive list Lastly, the rigorous application of the guidelines will of extramural relationships subject to this policy. These be particularly important in the case of persons exercis- examples have been divided into three groupings. ing significant authority. There are those in the Faculty Categories I(a), I(b), I(c), and I(d) consist of relation- of Medicine who have substantial influence over others ships that are generally not allowable, with certain de by virtue of their major role in professional appoint- minimis exceptions. Categories II(a) - (g) consist of rela- ments, promotions, tenure decisions, allocation of space tions that are generally allowable only after disclosure, and determination of salary. Typically these individuals review, and approval with oversight by the University or hold positions such as Chief Executive Officer (CEO affiliated Hospital with advice from a standing commit- or equivalent title) of an affiliated Hospital, Dean or tee of the Harvard Faculty of Medicine when requested. Executive Dean of the Faculty of Medicine, or Heads of 19 Departments. While the guidelines are applicable to all tion of the stock or similar ownership interest and Faculty, these individuals must take particular care not to research to be conducted. Situations that satisfy this become involved in research relationships that would lead requirement include stock or similar ownership inter- to their personal financial gain or that would adversely est acquired in arms-length transactions or by family affect the professional or academic advancement of junior gift sufficiently prior to the beginning of the research faculty members. to assure the lack of a relationship and stock or similar ownership interest acquired by inheritance. In any CATEGORY I (a), (b), (c), and (d) Activities are Generally such situation there must be complete independence Not Allowable. The only exceptions are conflicts that arise between a purchase decision or other acquisition and in extraordinary circumstances such as the recruitment of the research. a new Faculty Member, where a conflict may be allowed While meeting the above criteria excepts a Faculty 4. to continue for a finite time period with disclosure and Member from what would otherwise be an impermis- the approval of the Standing Committee, the Dean and sible Category I (a) or I (b) conflict, it does not except the CEO. a Faculty Member from other conflict categories such as Category II(e) which imposes an obligation to dis- Research Activities close a Financial Interest in the research in any publi- I(a) A Faculty Member Participating in Clinical cation or presentation. Research on a Technology owned by or contractually obligated(4) to a Business(5) in which the Faculty (b) A Faculty Member may consult for a Business in a Member, a member of his/her Family, or an Associated situation which would otherwise create an impermissible Entity has a consulting relationship, holds a stock or Category I (a) conflict only if all of the following condi- similar ownership interest, or has any other Financial tions are met: Interest, other than receipt of University- or Hospital- supervised Sponsored Research support or post-mar- The amount of money received by the Faculty 1. ket royalties under institutional royalty-sharing poli- Member for consulting relationships, fees or hono- cies.(6) raria from a given Business should not exceed $20,000 a year. Consulting relationships include contractual I(b) A Faculty Member receiving University- or relationships with a Business (or from an agent or Hospital-supervised Sponsored Research support other representative of such Business), service on advi- (whether in dollars or in kind) for Clinical Research sory boards and any other relationship whereby the or research which does not involve human subjects, Faculty Member receives, or has the right or expecta- from a Business in which he/she, a member of his/ tion to receive, income from a Business in exchange her Family, or an Associated Entity holds a stock or for services. Honoraria include commissioned papers similar ownership interest. Sponsored Research (and and occasional lectures (no more than four lectures a the prohibition of equity ownership) is considered to year) for which money is received, either directly or have ended when the term of the Sponsored Research indirectly, from a given Business (or from an agent or agreement has ended and publications reporting on other representative of such Business) the research are completed (or the decision made not to publish). It is the Faculty Member’s responsibility to While meeting the de minimis criteria above excepts 2. determine when that time has been reached. a Faculty Member from what would otherwise be a Category I(a) conflict, it does not exempt the Faculty De Minimus Exception to Category I (a) and I (b) Conflicts Member from other possible conflict categories such as (a) A Faculty Member may continue to hold stock or Category II(e) which imposes an obligation to disclose similar ownership interest in a Business in a situation a Financial Interest in the research in any publication which would otherwise create an impermissible Category or presentation. I (a) or I (b) conflict only if all of the following condi- tions are met: External Activities The stock or similar ownership interest must be in a 1. I(c) A full-time Faculty Member is not permitted to publicly held, widely traded Business. take an Executive Position (responsible for a mate- The current value of the stock or similar ownership 2. rial part of the operations of a Business such as Chief interest may not exceed $30,000 at any time. Executive Officer, Chief Operations Officer, Scientific 3. There must be no relationship between acquisi- Director or Medical Director) in a for-profit Business 20 engaged in commercial or research activities of a bio- Administrative Responsibilities medical nature. II(f) A Faculty Member taking administrative action I(d) A Faculty Member who serves on the Board of within the University or any affiliated Hospital which Directors of a Business is not permitted to Participate is beneficial to a Business in which he/she has a in Clinical Research on a Technology owned by or Financial Interest. obligated to the Business regardless of whether he/she has a Financial Interest in the Business and is not Applicants for Public Health Service and/or National permitted to receive Sponsored Research from that Science Foundation Research Funding Business regardless of whether he/she has an equity II(g) Under federal regulations(7) a Faculty Member interest in the Business. This provision does not apply who is an applicant for Public Health Service and/or to a Faculty Member who is a member of a Scientific National Science Foundation funding has a potential Advisory Board and who does not either hold an conflict under the federal regulations, if the Faculty Executive Position or serve on the Board of Directors. member, spouse and/or dependent children have a “significant financial interest,” which could directly CATEGORY II (a) - (g) Activities that May be Allowable and significantly affect the design, conduct or report- Only after Disclosure, Review, and Approval by University ing of the federally funded research. or Affiliated Hospital with Advice from the Standing Committee When Requested: “Significant Financial Interest” for Category II(g) Conflict Research Activities For the purposes of a Category II(g) conflict, as defined II(a) A Faculty Member conducting research exter- above, a “significant financial interest” consists of “any- nally that would ordinarily be conducted within the thing of monetary value” from the Business, including University or Hospitals. salary, consulting fees, honoraria, equity interests and intellectual property rights, with the exception of salaries, Committee Participation royalties and remuneration from University or an affili- II(b) A Faculty Member participating in the consider- ated Hospital, honoraria for presentations sponsored by ation by a committee of the FDA, other governmental public or non-profit entities or income from service on agency, or private insurer of Clinical Research on a advisory or review panels for public or non-profit enti- Technology which is owned by or contractually obli- ties. Also excepted for the purposes of a Category II(g) gated to a Business in which that Faculty Member, a conflict are salary, royalties or other payments that, when member of his/her Family, or an Associated Entity has aggregated for the Faculty Member, spouse and/or depen- a Financial Interest. dent children, are not expected to exceed $10,000 over the subsequent twelve months and equity interests, that, External Activities when similarly aggregated, do not exceed $10,000 in value II(c) A Faculty Member making clinical referrals to a or, if the monetary value cannot be ascertained, 5% own- Business in which such Faculty Member, a member of ership interest in the business. his/her Family, or an Associated Entity has a Financial Interest. Resolution of Category II(g) Conflict II(d) A Faculty Member possessing a Financial Interest Category II(g) conflict as defined above must be A in a Business which competes with the services pro- resolved by management, reduction or elimination, vided by the University or any Hospital with which the prior to the expenditure of funds from the Public Faculty Member is affiliated. Health Service and/or National Science Foundation. Possible resolution of Category II(g) conflicts may Public Disclosure include, but is not limited to, public disclosure of the II(e) A Faculty Member publishing or formally pre- significant financial interest, monitoring of research by senting research results, or providing expert commen- independent reviewers, modification of research plans, tary on a subject, without simultaneously disclosing disqualification from participation in Public Health any Financial Interest in a Business which owns or Service and/or National Science Foundation funded has a contractual relationship to the Technology being research, divestiture of the significant financial interest, reported or discussed or which sponsors the research and severance of relationships that create the Category being reported or discussed. II(g) conflict. 21 CATEGORY III Activities that are Ordinarily Allowable (b) Before embarking on a research project, a trainee Following Disclosure and, Where Necessary, the must be provided by the mentor with a clear descrip- Implementation of Oversight Procedures: tion of 1) the source of funding of the research project, including any corporate support of the research to be Research Activities undertaken, 2) any personal Financial Interest the men- III(a) A Faculty Member Participating in Clinical tor has in a Business, that sponsors the research, or has Research on a Technology developed by that Faculty or is seeking licensing rights in the research or in the Member or a member of his/her Family, unless the Technology being studied, and 3) any restrictions that activity falls under the guidelines of Category I. might be imposed on the scientific communication of the data. III(b) A Faculty Member assigning students, post-doc- toral fellows or other trainees to projects sponsored (c) Written approval must be obtained before a trainee by a for-profit Business in which the Faculty Member, can be assigned to conduct research which is sponsored a member of his/her Family, or an Associated Entity by a Business or which involves a Technology to which has a Financial Interest, unless the activity falls under the Business has licensing rights, and in which the mentor the guidelines of Category I. (See section on Mentor’s has any Financial Interest. Obligation to Students and Trainees below) In the case of graduate students (Ph.D., M.D./Ph.D., 1. M.P.H., and D.M.Sc. candidates), permission must be Board Memberships given by the chairperson (or desiginated Faculty mem- III(c) A Faculty Member serving on the Scientific ber or committee) for the graduate program and by Advisory Board of a Business from which that Faculty the mentor’s department chairperson Member or a member of his/her Family receives In the case of medical and dental students (M.D., 2. University- or Hospital-supervised Sponsored and D.M.D. degree candidates), permission must Research support or with which the University has be given by the mentor’s Medical School depart- a substantial contractual relationship known to the ment chairperson. Additionally, for research in the Faculty Member, unless the activity falls under the Quadrangle departments, permission must be give by guidelines of Category I. See Category I(d) above. the Dean for Academic and Clinical Programs. For research in the Hospital, permission must be given by External Activities the appropriate Faculty Dean. III(d) A Faculty Member assuming an Executive 3. In the case of postdoctoral fellows, permission must Position in a not-for-profit Business engaged in com- be given by the mentor’s Medical School department mercial or research activities of a biomedical nature. chairperson. CATEGORY IV Activities that are Routinely Allowable: (d) A trainee may appeal his/her involvement in any IV(a) A Faculty Member receiving royalties for published industrially Sponsored Research or research which scholarly work and other writings. involves Technology to which a Business has license rights IV(b) A Faculty Member receiving post market royalties when the trainee believes that he or she is being adversely under institutional royalty-sharing policies. affected by any conflict of interest (real or apparent) resulting from the mentor’s relations with the sponsor- MENTORS’ OBLIGATIONS TO STUDENTS AND ing Business or with any Business that may benefit from TRAINEES the trainee’s research or from the Sponsored Research (a) Trainees (medical students, graduate students and agreement. The appeal should be made as appropriate post doctoral fellows) must always be encouraged to con- to the Dean for Academic and Clinical Programs, the duct research in areas that optimize their training. Special Hospital’s Faculty Dean, and or the School’s or Hospital’s care must be taken to assure that a trainee’s research is Ombudsperson. not designed to (and does not appear to) enhance their mentor’s Financial Interest, and is not adversely affected (e) A Faculty Member must also disclose his or her by that interest or by contractual aspects of the Sponsored Financial Interests in a Business that sponsors the Research agreement that inhibit scientific communication research or which has or is seeking licensing rights in the or that commit intellectual property rights to the indus- research or in the Technology being studied, to members trial sponsor. of the research laboratory and/or research team. This includes disclosure to prospective students, trainees, and 22 new faculty before those individuals make a decision to (g) A “Financial Interest” is an interest in a Business join the laboratory or research team. consisting of: (1) any stock, stock option or similar own- ership interest in such Business, but excluding any interest APPENDIX A- OPERATING DEFINITIONS arising solely by reason of investment in such Business (a) An “Associated Entity” of a Faculty Member means by a mutual, pension, or other institutional investment any trust, organization or enterprise other than the fund over which the Faculty Member does not exercise University or any affiliated Hospital over which the control; or (2) receipt of, or the right or expectation Faculty Member, alone or together with his/her Family, to receive, any income from such Business (or from an exercises a controlling interest. agent or other representative of such Business), whether in the form of a fee (e.g., consulting), salary, allowance, (b) “Business” means any corporation, partnership, sole forbearance, forgiveness, interest in real or personal proprietorship, firm, franchise, association, organiza- property, dividend, royalty derived from the licensing of tion, holding company, joint stock company, receivership, Technology, rent, capital gain, real or personal property, business or real estate trust, or any other legal entity or any other form of compensation, or any combination organized for profit or charitable purposes, but excluding thereof. the University, any affiliated Hospital, any Private Medical Practice, or any other entity controlled by, controlling, or (h) “Hospital” means a Harvard Medical School affiliated under common control with the University or an affili- institution, including hospitals and health and research ated Hospital. institutions. (c) “Clinical Research” means any research or procedure (i) “To Participate” means to be part of the described involving human subjects in vivo or the use of human activity in any capacity, including but not limited to serv- samples for the development and evaluation of patient ing as the principal investigator, co-investigator, study therapies such as diagnostic tests, drug therapies, or designer, research collaborator, provider of direct patient medical devices. It includes early clinical studies, evalua- care, or author on a publication of the research study. The tive research, epidemiological studies and clinical trials. It term is not intended to apply to individuals who provide excludes research using commercially obtained de-identi- primarily technical support or who are purely advisory, fied human cell lines as well as commercially obtained with no direct access to the data (e.g., control over its col- de-identified human tissue. It also excludes research that lection or analysis), unless they are in a position to influ- uses human tissue obtained from institutional tissue ence the study’s results or have privileged information banks where the individual identifiers are unknown to as to the outcome. This definition applies to a Faculty the researcher. In general, the term includes all research Member receiving sponsored research or participating in required to be reviewed by an institution’s Institutional non-clinical research in the same way that it applies to a Review Board.(8) Faculty Member participating in clinical research, includ- ing such activities as collaboration, study design, and (d) “Executive Position” refers to any position which authorship. includes fiduciary and other responsibilities for a material segment of the operation or management of a Business. It (j) “Private Medical Practice” means the professional specifically includes the titles of “Scientific Director” and services rendered by a physician, including departmental “Medical Director”. practice plans, and the procedures integral to those ser- vices. (e) “Faculty Member” means any person possess- ing either a full- or part-time academic or fellowship (k) “Sponsored Research” (9) means research, training appointment in the Faculty of Medicine. Full-time and instructional projects involving funds, materials, or Faculty Members on sabbatical or other paid leave are other compensation from outside sources under agree- considered full-time for the purposes of the Policy. Full- ments which contain any of the following. time Faculty Members on approved unpaid leave are not 1.The agreement binds the University or Hospital to considered full-time for these purposes. a line of scholarly or scientific inquiry specified to a substantial level of detail. Such specificity may be indi- (f) The “Family” of a Faculty Member includes his/her cated by a plan, by the stipulation of requirements for spouse, minor/dependent children, and other persons liv- orderly testing or validation of particular approaches, ing in the same household. or by the designation of performance targets. 23 2.A line-item budget is involved. A line-item budget such process, whether by virtue of a Faculty Member’s details expenses by activity, function or project period. refusal to respond or by his/her responding with incom- The designation of overhead (or indirect costs) quali- plete or knowingly inaccurate information, (b) failures fies a budget as "line item." to remedy conflicts, and (c) failures to comply with a 3.Financial reports are required. prescribed oversight plan. Such cases will be forwarded to 4.The award is subject to external audit. the Standing Committee for review. Based on its review, 5.Unexpended funds must be returned to the sponsor the Committee will make recommendations to the Dean at the conclusion of the project. for further action. In all cases, Faculty Members will be 6.The agreement provides for the disposition of either provided the explicit opportunity to respond in person tangible or intangible properties which may result and in writing to the issues raised in the course of such from the activity. Tangible properties include equip- review. Any such written response will be appended to ment, records, technical reports, theses or dissertations. the Committee’s report for review by the Dean and, in Intangible properties include rights in data, copyrights the case of Hospital-based Faculty Members, the Hospital or inventions. CEO. The Committee will also be available to advise affiliated Hospitals on the application of the guidelines to (l) “Technology” means any compound, drug, device, specific cases as disclosed by their Faculty. diagnostic, medical or surgical procedure intended for use in health care or health care delivery. DISCLOSURE PROCESS AND IMPLEMENTATION The Office of the Dean has the ultimate responsibility for STANDING COMMITTEE ON CONFLICTS OF confirming compliance by all Faculty Members with the INTEREST AND COMMITMENT policies of the Faculty of Medicine. Such responsibility The Dean of the Faculty of Medicine will appoint a extends not only to Quadrangle-based Faculty but also to standing committee. This Standing Committee on Faculty based in the affiliated Hospitals. Conflicts of Interest and Commitment will be comprised of representatives from both the clinical and preclinical Submission of Disclosure Forms faculty and will be responsible for reviewing cases which 1. The Office of the Dean is responsible for the dissemi- are brought to its attention by the Office of the Dean. It nation, collection and review of the disclosure forms will review such cases and will make recommendations for members of the Faculty of Medicine. Each Hospital for conflict resolution to the Dean. The Committee will will designate a responsible office or individual to develop procedures for implementing the disclosure and serve as a liaison representative to the Office of the approval process, the establishment of oversight proto- Dean. cols, and the handling of cases involving non-compliance 2. members of the Faculty of Medicine, both full- All and breach, and the designing of appropriate subsequent and part-time, are required to complete and submit disciplinary actions. a disclosure form on a regular basis. Updated forms The Standing Committee is responsible for review- must be submitted throughout the year if changes ing the implementation of the policy on a regular basis arise which the Faculty Member believes may either: and providing oversight to assure that the policy is (a) give rise to a conflict of interest or (b) eliminate a applied consistently to the Faculty including both those conflict previously disclosed. based in the Quadrangle and those based in the affili- 3. Individuals holding fellowship positions are not ated Hospitals. The Standing Committee is responsible required to complete and submit a disclosure form for reviewing cases which may be referred to it where unless they believe that they are involved in or may be the application of the policy to an individual is unclear. involved in a situation which gives rise to a conflict Finally, the Standing Committee will continue to review of interest. The Office of the Dean is responsible for both the policies of other institutions and any govern- sending individuals who hold fellowship positions ment requirements in this area and to recommend chang- appropriate notification of their obligations under the es to the policy when appropriate. policy. The Office of the Dean is responsible for overseeing 4. Disclosure forms should be returned to the Office of the implementation of the policy by all affiliated institu- the Dean for initial review. The Office of the Dean will tions, including the process and mechanism for disclosure be responsible for providing the forms to the designat- and resolution. This Office will review all breaches of the ed Hospital liaison representative for Hospital review. disclosure process, including (a) failures to comply with In consultation with the Office of the Dean, each 24 Hospital will establish its own mechanism for review Establishment of Oversight Protocols of the forms to ensure compliance with the disclosure The hospital CEO (in the case of hospital-based Faculty) process. This mechanism will include written remind- and the Standing Committee (in the case of Quadrangle- ers for Faculty Members to return disclosure forms, based Faculty) are responsible for designing and propos- as well as statements encouraging Faculty Members ing appropriate oversight mechanisms. They are expect- to seek assistance in the event of questions or special ed to seek advice from individuals outside as well as circumstances. Offices providing such assistance will within their institutions in preparing such mechanisms. be designated in each of the Hospitals as well as in the The associated rationale and details must be presented to Quadrangle. Regardless of the mechanism selected, the Office of the Dean for review and approval. disclosure forms which implicate any conflict category should be reviewed regularly by the department head. Implementation Process under Public Health Service The disclosure forms will be considered strictly and National Science Foundation Regulations confidential, and it will be the responsibility of the 1. Disclosure required by the Public Health Service designated offices in the Quadrangle and Hospitals and National Science Foundation regulations should to ensure that the information disclosed in the forms be made on appropriate forms at the time of grant is available only to the individuals duly charged with application submission to the appropriate offices in the responsibility for review. Similarly, offices of the Quadrangle and affiliated institutions. department heads, the Dean and the President will 2. Resolution of impermissible Category I(a) and I(b) be required to establish means for the preservation of conflicts identified in the federal application dis- confidentiality. closure process should be made by the appropriate 5. the case of Faculty Members who hold the posi- In Quadrangle or affiliated Hospital officials. Notice of tions of CEO (or equivalent title) of an affiliated such resolution should be forwarded to the Office hospital, Dean or Executive Dean of the Faculty of for Research Issues in the Office of the Dean. The Medicine, or heads of departments, the regular, as Standing Committee will review these and other reso- well as interim, disclosure and review processes will lutions as appropriate. proceed as follows: 3. Decisions as to the appropriate resolutions of • chairs of the preclinical departments will report Category II(g) conflicts identified in the federal appli- directly to the Dean of the Faculty of Medicine; cation process should be made by the appropriate • chairs of the clinical departments will report direct- Quadrangle or affiliated Hospital officials. Notice of ly to the Hospital CEO, with copies to the Dean; such resolutions should be forwarded to the Office • Dean and Executive Deans of the Faculty of the for Research Issues of the Office of the Dean. The Medicine will report to the University President; Standing Committee will not as a matter of course • hospital CEOs (or individuals with equivalent review such resolution decisions, but reserves the title) will report to the Executive Committee of the right to do so. Board of Trustees of the hospital, with copies to the 4. the case of Public Health Service funding appli- In Dean. cants, appropriate Quadrangle and affiliated Hospital officials are responsible for notifying the Public Review of Disclosure Forms Health Service, prior to the institution’s expenditure Following disclosure and upon receipt of disclosure of any funds under the award, of the existence, but forms from the Office of the Dean, each institution will not the nature, of a conflict and that the conflict review the forms for its Faculty and the Office of the will be managed, reduced or eliminated, at least on Dean will review forms for Quadrangle-based faculty. an interim basis, within 60 days after it is identified. Each institution will notify the Office for Research Issues Such officials are also responsible for informing the in the Office of the Dean of the resolution of identified Public Health Service that corrective action has been Category 1(a), 1(b), I(c), and I(d) conflicts as well as or will be taken when an applicant Faculty Member those instances that may require review and approval by does not comply with the policy. the Standing Committee. 5. the case of National Science Foundation funding In The CEOs and the department heads are expected to applicants, appropriate Quadrangle and affiliated notify the Office of the Dean immediately of any cases Hospital officials are responsible for certifying to that require review by the Standing Committee, no mat- the National Science Foundation that all identified ter when the cases occur. conflicts have been satisfactorily managed, reduced or 25 eliminated prior to the institution’s expenditure of any 4 By license or exercise of an option to license. (go back to funds under the award. source) 5 The definition of ‘Business’ excludes the University, any COMPLIANCE RESPONSIBILITY affiliated hospital, any Private Medical Practice or any enti- The Faculty of Medicine expects its members to com- ty controlled by, controlling, or under common control with ply fully and promptly with the policy, including the the University or affiliated hospital. (go back to source) requirements of disclosure. However, it is anticipated that instances of technical non-compliance will occur. It will 6 The exemption for royalties under institutional royalty- be the responsibility of the Standing Committee to make sharing policies applies to post-market royalties through recommendations to the Office of the Dean for resolution institutional royalty agreements and not to a Faculty of such cases. Member’s share in equity, licensing fees, milestones pay- Instances of deliberate breach of policy, including fail- ments and other payments received by the institution as ure to file or knowingly filing an incomplete, erroneous, part of licensing or other agreements with a Business in or misleading disclosure form, violations of the guidelines which the investigator has a right to share, that are some- or failure to comply with prescribed monitoring proce- times characterized as “royalties”. A Faculty Member’s share dures, will be adjudicated in accordance with applicable in such non post-market royalties should be considered to be disciplinary policies and procedures of the Faculty of personal Financial Interests and subject as such to the provi- Medicine and of the affiliated hospitals. Possible sanctions sions of the Policy. (go back to source) will include the following: 1. Formal admonition; 7 Public Health Service Final Rule 42 CFR Part 50 and 45 2. he inclusion in the Faculty Member’s file of a T CFR Part 94; National Science Foundation Rule 59 FR 3308 letter from the Office of the Dean indicating that and 60 FR 35820. (go back to source) the individual’s good standing as a member of the Faculty has been called into question; 8 In a time of increasing translational research, it is difficult 3. neligibility of the Faculty Member for grant appli- I to arrive at a definition of “clinical research” that precisely cations, Institutional Review Board (IRB) approval, delineates research having a direct and immediate impact or supervision of graduate students; on human health. There may be pre-clinical studies, for 4. Non-renewal of appointment; example some kinds of research in animal models or certain 5. ismissal from the Faculty of Medicine. D translational research, that can have as direct an influence on human health as do clinical studies involving human Adopted by the Faculty Council, March 22, 1990 subjects. While the recommended definition of “clinical Amendments Adopted September 22, 1993 research” does not include such pre-clinical research. Faculty Amendments Adopted September 20, 1995 Members and institutions should recognize the potential for Adopted by the Harvard Medical Center, May 16, 1990 conflict of interest where the Faculty Member has a related Amendments Adopted December 13, 1993 financial interest allowed under Category 1(b). (go back to Amendments Adopted December 18, 1995 source) Amended May 25, 2000 Amended May 26, 2004 9 Adopted from the Harvard University Principal Investigator’s Handbook, 1988. (go back to source) Footnotes: 1 See Statement on Research Sponsored by Industry. (go © 1996 President and Fellows of Harvard College. All rights back to source) reserved. Materials adapted from the paper version of Faculty Policies on Integrity in Science, available from the 2A similar parenthetical insert may be inferred throughout Office for Research Issues, Harvard Medical School, this document. (go back to source) 25 Shattuck Street, Boston, MA 02115. (617) 432-3191. 3A series of operating definitions of terms appearing with initial capital letters is found in Appendix A of this policy. (go back to source) 26 Appendix 2 UNIVERSITY OF PENNSYLVANIA SCHOOL OF MEDICINE II.E.10. Conflict of Interest Policy for Faculty Conflict of Interest in the Allocation of Time and Effort Members AVAILABLE AT: www.upenn. to Extramural Activities edu/assoc-provost/handbook/ii_e_10.html. The University recognizes that its faculty members are Accessed on August 9, 2006. [See also, Human not employees in the usual sense, and that a precise allo- Resources Policy Manual, Policy No. 003 on Use cation of academic time and effort is inappropriate. Their of University Property] (Source: Office of the pursuit of knowledge in their areas of competence is Provost, Almanac, March 8, 1983 revised 1991) presumed to be a lifelong commitment. A limited associa- tion of faculty members with government, professional Introduction agencies, and public or private organizations is appropri- This policy applies in full to all Standing Faculty, Standing ate, especially when it may enhance their competence as Faculty-Clinician-Educators, and all full-time members of scholars. both the Associated Faculty and Academic Support Staff, hereinafter simply designated faculty members. Parts of it Policy on Extent of Extramural Activities. Forms of also apply to those with part-time faculty appointments; extramural activity include part-time engagement for a these cases are noted in the appropriate sections. The fee as a technical or professional consultant or practitio- details of this policy derive from the following general ner and formation or association with business enterpris- obligations: es or non-profit organizations.* In principle, both such associations are approved under the following conditions: a. employees are required to conform to the mores All a. Faculty members should not engage in such extramu- and ethical standards of the University and the rules ral associations to an extent that detracts significantly promulgated to enforce them. from their availability for normal academic duties. b. Employment as a faculty member presumes a primary These commitments in aggregate should not exceed commitment of time and intellectual resources to the one day per seven day week during the academic year. academic mission of the University and its functioning Exceptions to this will be permitted only in unusual as a community. circumstances and require the specific approval of The following sections cite specific types of activity that the president or provost, the academic dean and the have commonly been found to conflict with these obliga- department chair. tions, and the procedures and regulations that have been b. Faculty members shall make known to their depart- devised to identify and resolve such conflicts. They are ment chairs and academic deans the prospect of each intended to serve as examples and not as a comprehen- continuing engagement, including, at least, all engage- sive compilation. Situations not covered by them will be ments expected to extend for a substantial portion of judged in the light of the above general obligations. an academic term. Faculty members should decide to Examples of actions that run counter to the first gen- enter a relationship only if, after discussion with their eral obligation include nepotism, discrimination on the department chairs and academic deans, there is con- basis of irrelevant characteristics, inappropriate use of currence that the proposed engagement will not con- the University’s name, and exploitation of any aspect of flict with the faculty members’ professional obligations association with the University for unacceptable purposes to the University, or with the University’s outstanding or private gain. They are proscribed at all times for all or prospective commitments for teaching and research. faculty members, extending to those in part-time employ- c. addition to the prospective disclosure cited above, In ment as noted in the relevant sections of this document. all faculty members must report on the extent of their Excessive commitment of time or mental effort to extra- extramural activities of all types as detailed below. mural engagements or other non-University activities during the academic year constitutes a violation of the Conflict of Financial Interest between the University second general obligation. As used in this policy, the and Extramural Organizations academic year is defined for each faculty member as that Members of the faculty or of their immediate families portion of the year during which he or she receives a sal- (including parents, children, siblings, spouse) may have ary from the University for services. significant investments or interests or hold official posi- tions in extramural business organizations, whether or 27 not they have undertaken to perform continuing work or business enterprise; and/or services for them. Such economic or official relationships b.Principal investigator or other substantial responsi- are of concern if: bilities for the satisfaction of the engagement. a. The organizations are engaged in activities that parallel activities in which the University is cur- By requiring that each engagement be offered to the rently or prospectively engaged, and in which fac- University, the following ends are served: ulty members play (or might appropriately play) a 1. The disclosure of the type, scope and extent of role in their academic capacity; or extramural activities is achieved, in accord with b. The organizations have a present or prospective University policy; relationship with the University, e.g., as suppliers 2. The decision as to whether an engagement is of goods or services or as parties to research con- appropriately undertaken as a University or tracts, and the conduct of those relationships may extramural activity is shared with the University involve faculty members in their academic capaci- administration, thereby avoiding possible con- ties; or flicts of interest, and the appearance of such c. The engagements undertaken by faculty members conflicts. under the aegis of extramural business organiza- tions might be suitable and appropriate activities Faculty members intending to conduct engagements in for execution within the University. business enterprises with which they are associated shall disclose in writing to their department chairs and deans: Policy on Disclosure of Relationships with a. The nature and terms of the proposed enterprise, Organizations that are Suppliers or Potential and Competitors of the University b. The reasons why it should be conducted as an In any of these situations, faculty members shall be extramural activity. required to report the facts and circumstances to their department chairs and academic deans so that appropri- If the chairs and deans agree that the engagements are ate steps may be taken to avoid conflicts of interest, espe- not appropriate as a University activity, and if they con- cially ones in which faculty members may benefit from a clude that the other conditions of the extramural consult- knowledge of confidential information. ing policies of the University will be met, then they will In the foregoing it assumed that those with part-time advise the faculty members to proceed. Otherwise, they faculty appointments will not normally participate in may require that the engagements be conducted within University decisions that could engender such conflicts the University. of interest for them. Whenever this condition does not obtain, the policy stated above extends to them. Disclosure of University Affiliation in Publications of Furthermore, in any circumstances in which part-time Extramural Organizations faculty members are engaged in externally sponsored Faculty members who form or associate with extramural research projects contracted with the University, or in business enterprises or non-profit organizations should which they stand to benefit from a knowledge of confi- exercise particular care that their University affiliation dential information, full disclosure of their relationships is appropriately cited in publications of such organiza- with relevant extramural organizations and of the facts tions. Problems that can arise from failure to observe this pertaining to any potential conflict is required. injunction include: a. Such an organization, by reason of the participa- Policy on Acceptance of Engagements through tion of faculty members, might be considered to Extramural Organizations have some formal or informal relationship to the Faculty members with positions or connections in extra- University. mural organizations who wish to undertake engagements b. Faculty members by reason of their positions in through those organizations rather than the University such organizations might be expected to discharge are obliged to offer first to the University each such duties and responsibilities for those organizations engagement (grant, contract, client, etc.) in which they that would be inconsistent with their primary duty would assume one or both of the following relationships to the University. to the engagement: a. O ner, executive or other principal decision-mak- w Disclaiming University Relationships. A business ing position responsible for the conduct of that enterprise or non-profit organization, with which a fac- 28 ulty member has a connection, may release to the public interest of the University of Pennsylvania, J. Smith from time to time publications concerning itself and its will resolve such conflict in favor of the University of activities. In all such publications it may be desirable Pennsylvania. and, in many cases, required by law that a faculty mem- ber’s affiliation with the University be disclosed. The Provost shall have the power to require such a The impact of such disclosure will depend on the disclosure in any instance where he or she adjudges it circumstances. At one extreme a faculty member might necessary. serve as a member of the board of directors of an established business or non-profit organization, where Conflict of Interest in Externally Sponsored Research there is not even a remote implication that such orga- Regulations concerning sponsored research may be nization is in any way connected with the University of found in the “Guidelines for the Conduct of Sponsored Pennsylvania. At the other extreme all or a large number Research”. Further details and regulations may be found of the principals of an organization (officers, directors, in the current Research Investigators’ Handbook, avail- promoters and substantial shareholders) may be fac- able from the Office of Research Administration, and ulty members. In such cases, there is a strong implica- Guidelines for Extramural Activities of Faculty of the tion that the organization may be connected with the University of Pennsylvania Medical Center and Health University of Pennsylvania, even that the University System. bears some responsibility for its activities and success. In The University encourages its faculty members, these cases, an express statement of the form, including those in part-time employment, to participate in externally sponsored research projects whether sup- The ___________________ has no connection, directly ported by government agencies, foundations, associa- or indirectly, with the University of Pennsylvania. tions, or other non-profit organizations; or by corpora- tions, partnerships or other for-profit entities. In any in prominent type, should be included in all publica- sponsored project, faculty members are expected to tions released by such organization. The provost shall avoid use of the project for their private financial gain have the power to require such a statement to be includ- other than in the form of salary support or of royal- ed in all organizational publications that refer to faculty ties resulting from commercialization of intellectual members, when it is in his or her judgment necessary. property rights in accordance with University policies. The foregoing rules extend to part-time faculty mem- However, there may be unusual circumstances where the bers, when their association with the University is men- interests of the University would be served if a faculty tioned in an organizational publication. participant in a sponsored project were to assume an Affirmation of Obligations to the University. A entrepreneurial role, as, for example, by direct participa- faculty member may have a position of responsibility tion in a private enterprise providing funds in support (continuing or temporary) with an extramural business of the project. Assumption of such a role would not be a organization. In such cases it should be made clear in violation of these guidelines if approved in advance and any publications of the organization that the obliga- reviewed periodically by the relevant Dean and the Vice tions, in terms of both time and responsibility, of the Provost for Research. Examples of situations from which faculty member to the extramural organization are conflicts of interest may arise include, but are not lim- limited by and subject to the policy of the University of ited to, the following: Pennsylvania. This alerts both the public and the faculty a. ndertaking or orientation of sponsored research U member’s business associates that duties to the extramu- to serve the needs of a private agency or enterprise ral organization are thus limited. This is especially neces- in which a responsible staff member has an interest. sary in the case of corporate officers who are normally b. urchase of major equipment, instruments, P regarded as owing a comprehensive fiduciary duty to the materials or other items for externally sponsored corporation and its shareholders. The suggested format research from any agency or enterprise in which a for such a disclosure is: responsible staff member has an interest. Smith, a vice president of this corporation, J. c. Acceptance of any limitations on the free publica- is a member of the faculty of the University of tion of and access to the results of any sponsored Pennsylvania and as such is subject to limitations by research. Exception may be granted by the provost the University on the time that may be devoted to for privileged information, but only in the form the affairs of this corporation. In any instance where of a delay in the release of such information. The the interest of this corporation may conflict with the delay will only on rare occasions exceed three 29 months. Those wishing to engage in research of a Requirements for Reporting Extramural Activities and kind whose results cannot be so disseminated may Obligations only do so as an extramural consulting activity At the end of each academic year, each faculty member under the conditions previously described. shall submit to his or her department chair and dean a d. ransmission to any private agency or enterprise, T report of his or her extramural activities during that year, use for personal gain, or other unauthorized use containing the following information: of the work product, results, materials, records, or a. Number of days (or hours, if preferred) of extramu- information gathered from sponsored research that ral activities for fee (include consulting, professional is not made generally available through publication practice, outside teaching commitments, lectures for or other free access. honoraria, etc.); e. Acceptance of gratuities or special favors from a pri- b. ames of organizations (government agencies, pri- N vate agency or enterprise with which the University vate firms, partnerships, etc.) for which the extra- conducts business in connection with a sponsored mural activities conducted represented a continuing research project. engagement; c. Number of days (or hours, if preferred) of extramu- Disclosure to Responsible University Officials. Before ral activities on behalf of businb ess enterprises in participating in any sponsored research project, all faculty which they have financial interests or official posi- members must give written notice of their extramural tions. consulting relationships or other sponsored research d. ames of business organizations in which the fac- N projects that may relate in any way to the project to the ulty member is a significant owner, partner, officer, appropriate department chairs and through them to the director, or staff member, etc. deans and vice provost for research. Any significant finan- cial or managerial interests that may relate in any way to The last item shall also be reported by all part-time the project must be disclosed in writing to the vice pro- faculty members for whom any of the following condi- vost. Any faculty members engaged in sponsored research tions obtain: projects must disclose in the same manner any change • The organization is a supplier of the University and in their outside activities or interests. In the light of such the part-time faculty member participates in the disclosures, the University will take appropriate steps to decision to engage its services. neutralize or eliminate potential conflicts of interest. Distribution of Effort. The sponsoring agency sup- •The organization supplies goods or services to the porting research must not be misled as to the amount of University to be used in the performance of exter- intellectual effort that faculty members are actually devot- nally sponsored research projects in which the part- ing to these research projects. A system of precise time time faculty member participates. accounting is incompatible with the inherent character of the work of faculty members, because the various func- •The part-time faculty member is privy to confiden- tions that they perform are closely interrelated and do not tial University information that could be used to the conform to any meaningful division of a standard work business advantage of the organization. week. However, if externally sponsored research agree- ments provide that faculty members will devote a definite •The affiliation of the part-time faculty member fraction of effort to the projects, or if it is agreed that they with the University may be mentioned in any publi- will assume specified responsibilities in relation to such cation of the organization. research, demonstrable relationships between the stated efforts or responsibilities and the actual extent of their Forms for the reporting of extramural activity are involvement are to be expected. Each faculty member, in available from the Office of the Provost. such circumstances, shall confirm the fraction of effort All faculty members must also report on a continuing devoted to the projects in the effort reports required of all and timely basis to the appropriate administrators the rel- faculty members who are so engaged. evant circumstances, as noted in the sections cited, when- Advice and Guidance. Any questions concerning ever any of the following conditions are met: potential conflicts of interest, appropriate distribution of a.They have or wish to initiate a relationship effort, or other problems associated with externally spon- with an extramural business organization that sored research, should be addressed to the office of the is or may become a supplier or competitor of Vice Provost for Research. the University (see section II.E.10 on Policy on 30 Disclosure of Relationships with Organizations employees of the University arising from the family that are Suppliers or Potential Competitors of the relationship, the department chair must outline in writ- University). ing the steps being taken to avoid or manage conflicts of b. hey wish to undertake an engagement (grant, T interest or the appearance of such conflicts, subject to contract, client, etc.) through an extramural approval by the dean. Deans will report such arrange- organization (see section II.E.10 on Policy on ments to the provost in the course of normal adminis- Acceptance of Engagements through Extramural trative oversight. Organizations). No faculty member shall participate in any other c.They intend to participate in a sponsored research decision, including determining the salary, teaching and/ project that may be related to their other spon- or administrative assignments, and space assignments, sored research projects, to any of their extramural directly and individually affecting a member of his or consulting relationships, or to any organization her family on the Standing Faculty or Associated Faculty. in which they have significant managerial or financial interests (see section II.E.10 on Policy on B. Family Members Appointed to Non-faculty Acceptance of Engagements through Extramural Positions Organizations). Faculty members should take care to avoid conflicts Employment of More than One Family Member (Source: of interest or the appearance of such conflicts in the Office of the Provost; Almanac, December 16, 1997) employment of, and in any ongoing University-related professional relationship with, a family member in University policy permits the employment of more a non-faculty position. All decisions regarding such than one member of a family (defined as being related employment should be conducted in strict conformance by blood, marriage and former marriage, or adoption, or with the Human Resources Policy. defined as partners recognized under University benefits policy), whether or not the persons concerned are in C. Reporting the same academic or administrative department. The In the course of normal administrative oversight, depart- University’s primary concern in such cases of appoint- ment chairs or other heads of department will report ment, as in all others, is that faculty or staff members periodically to deans, and deans will report to the pro- are the best candidates with respect to the requisite vost, on steps that have been taken to avoid or manage qualifications for employment. The University has a conflicts of interest or the appearance of such conflicts parallel concern, however, in the avoidance of a conflict among faculty members and/or academic administrators of interest or the appearance of such conflict, where an who are related as family. In each case, the faculty mem- employee’s professional decisions or actions pertaining bers and/or academic administrators who are subject to the performance of his or her job would be colored to such reports shall receive copies of such reports on a by considerations arising from a family relationship with timely basis. another employee. The University also recognizes that These requirements extend to part-time faculty the appointment of two or more family members, espe- appointments whenever such a person may exercise cially within the same department, could generate pres- decision-making power over the employment and/or sures and prejudice among colleagues. To guard against administration of a family member employed by the such conflicts and abuses, the following rules must be University. observed: * Including part-time employment by another academic A. Family Members Appointed to the Faculty institution. Such employment may be inappropriate for No faculty member shall participate in any way whatso- a faculty member whose primary commitment of time ever in the decision to employ, promote, reappoint, or and intellectual resources is to the academic mission of terminate the appointment of a member of his or her the University of Pennsylvania and its functioning as a family on the Standing Faculty or the Associated Faculty. community. A full-time faculty member who consid- Any proposal to employ as a faculty member a person ers employment for research or teaching at another who is related to a member of the faculty or adminis- academic institution during the period of his or her tration must be brought to the attention of the dean employment by the University should treat this prospec- before an offer of appointment is made. In cases where tive employment as a continuing engagement and follow there is a potential conflict of interest in the professional the procedures outlined below. relationships of family members or with respect to other 31 Appendix 3 Selected Hypothetical Examples of Difficult Conflicts of Interest (1) The Chair of the XXX Department has a startup both entities. These duties include: company that proposes to sponsor the research of Dr. Q Duty of reasonable care to the company—to maximize Doe, assistant professor of XXX. shareholder profit. The chair supervises the young faculty member (sal- Q Duty of loyalty to both—to the best interests of the ary, space, resources, promotion). company/institution. Problem 1: Chair’s official status raises this scenario to an Q Duty to follow Doctrine of Corporate Opportunity—to institutional conflict of interest (ICOI). preserve any business opportunities for the corporation. Problem 2: Raises issues of perception by other faculty of Q Duty to avoid conflicts of interest. potential favoritism. Recusal is a safe harbor but only if it is “real;” difficult (2) Department Chair has an extensive consulting rela- for major shareholders. tionship with a company that proposes to sponsor the Several corporate sanctions are available for corporate Chair’s research—an example of a personal COI. officers who breach their duties. The Chair assigns the project to Assistant Professor Doe as the PI to avoid the COI but will remain (7) CASH Co. wants to sell major equipment to the involved. clinical system. To sweeten the deal, it offers to fund Problem: Arguably an ICOI because the authority of fellowships, hospital space, and/or research tied to an Chair could influence the outcome. agreement that all supplies for the equipment will be purchased from CASH. (3) EVP/Dean/COO invests $50K to take institutional Problem: Potential ICOI because funding is a write-off equity in Dr. Smith’s startup company to develop vac- for CASH but has the appearance of being a bribe (always cines (in good, but short-sighted, faith). think of defending against headline news.) Plus, the IRS Problem 1: Company wants to fund research in the insti- sees this practice as “excess benefits, unless extensive fair tution (clinical research—usually a non-starter!) market value studies are documented Problem 2: Dr. Smith wants to pipeline all of his future technology to his company. (8) Dr. Bart receives $50,000/yr in consulting or other personal fees and/or has equity interests (stock, (4) Dr. Smith asks the university to license the vaccine options) in FLOW Co. technology that he generated in his university labora- FLOW proposes to pay Dr. Bart personally (not tory to his company. through the institution) if Dr. Bart will conduct a train- Problem: ICOI because institution has equity in company ing course for FLOW (using FLOW’S devices). FLOW and would receive royalties. Institution has duty to ensure wants Dr. Bart to use the institution’s resources (space, that the technology is transferred in the way that is most personnel, resources, hospital facilities, patients) to likely to benefit the public. teach the course. “Students” could include other physi- cians and fellows or the personnel of BART. (5) Dr. Zee, the Service Chief, routinely recommends Problem 1: This is a personal COI for Dr. Bart. It the surgical sutures, stents, and other devices pur- becomes increasingly serious, depending on the resources chased by the hospital. Dr. Zee is compensated >$10K that are used. It gets most serious if she were to involve each as a consultant and speaker for the suture com- patients. pany and holds >$20K stock in the device company. Problem 2: Institutional COI if FLOW also provides a Problem: ICOI with the institutional vendor policy. “gift” to the Department (e.g. funding for fellows; funds to name a surgery suite). (6) Dr. Lee holds a position as officer (or member of the board of directors) of a company that proposes to sponsor research or do business with institution. Problems: ICOI because Dr. Lee has fiduciary duties to 32 Appendix 4 SHARED RESPONSIBILITY, INDIVIDUAL INTEGRITY: SCIENTISTS ADDRESSING CONFLICTS OF INTEREST IN BIOMEDICAL RESEARCH March 13, 2006 Federation of American Societies of Experimental Guiding principle 9: Investigators shall be aware of and Biology (FASEB) The FASEB Board of Directors adhere to individual journal policies on disclosure of approved this report on December 9, 2005. industry relationships. The guiding principles to aid investigators in address- Guiding principle 10: Consulting and advisory board ing these challenges are: relationships shall be carried out in a transparent and Guiding principle 1: Investigators have a responsibility accountable manner and be disclosed as they are initi- and commitment to conduct scientific activities objec- ated. tively and with the highest professional standards. Guiding Principle 11: When investigators have consult- Guiding principle 2: The primary responsibility of full- ing relationships with an investment firm related to their time investigators is to the institution. Outside activi- area of expertise, all parties shall be aware of the specific ties shall complement, not compromise, institutional circumstances involved. responsibilities. Guiding principle 12: Investigators shall not use federal Guiding principle 3: It is appropriate and beneficial for funds to the benefit of a company, unless this is the academic institutions to develop and enforce their own explicit purpose of the mechanism used to fund the mechanisms of review and oversight of investigator rela- research (e.g., Small Business Innovation Research and tionships with industry. similar grants). Guiding principle 4: The academic community can Guiding principle 13: When investigators own signifi- and shall monitor itself through peer review of industry cant equity in a company with which research is con- relationships. Institutional committees that include peer ducted, all parties shall be aware of the special circum- members from the same institution are appropriate and stances involved. effective in reviewing disclosures of investigators’ indus- Guiding principle 14: When holding a significant role try relationships. in a start-up company, investigators shall be guided by Guiding principle 5: Investigators want and need clear agreed-upon limits to the scope of the relationship. guidance, efficient processes, and adequate support Guiding principle 15: Investigators shall be aware of and mechanisms from their institution throughout their par- adhere to requirements of federal funding related to dis- ticipation in industry relationships. closure of inventions. Investigators shall adhere to patent Guiding principle 6: Investigators shall have access to, law and institutional requirements. and be involved in the analysis and/or interpretation of Guiding principle 16: Investigators shall not seek to all data generated in the research. influence their institution’s technology transfer decisions Guiding principle 7: Mutual understanding of con- for personal gain. straints, principles, and policies regarding access, analy- Guiding principle 17: A mentor’s outside commercial sis, and dissemination of research information, data, and interests shall avoid impeding a trainee’s timely progress materials among investigators and their students and toward his/her degree, restricting a trainee’s right to trainees, institutions, and sponsors is beneficial. publish his/her dissertation research in a timely manner, Guiding principle 8: Investigators shall not enter into compromising a trainee’s career progress, or restricting a agreements with companies that prevent publication of trainee’s freedom of inquiry. research results. Pre-publication review by an industry sponsor shall occur in a timely manner (no more than Guiding principle 18: Mentors and institutions should thirty to sixty days) so as not tounnecessarily delay study make trainees aware of their rights and responsibilities publication. in industry relationships. 33 Guiding principle 19: Investigators shall regard all sig- Approved by AAMC Executive Committee, January nificant financial interests in research involving human 6, 2006 (Excerpt) (Full text available at www.aamc.org/ subjects as potentially problematic and thus requiring research/clinicaltrialsreporting/clinicaltrialsreporting.pdf close scrutiny. Accessed August 10, 2006). Appendix 5 Principles for Protecting Integrity in the Conduct and Reporting of Clinical Trials Issue Public concern is high regarding the timely and intervention” means “any intervention used to modify a complete reporting of clinical trial results, primarily when health outcome”, including “drugs, surgical procedures, the trials are sponsored by the drug, biologicals, or device devices, behavioral treatments, process-of-care changes, industries. Because academic researchers and their insti- and the like.”1 This definition explicitly excludes phase 1 tutions often play a prominent role in such trials, these and early phase 2 studies (but not all late phase 2 studies), concerns challenge the integrity of the academic medical and it includes all phase 3 and 4 clinical trials, including research community as well as the sponsors of the trials. studies of new indications for approved products. Background Despite a number of external initiatives Publications and Public Availability that have heightened standards for reporting clinical trial of Research Results results, the AAMC has been troubled by evidence that sig- nificant variation continues to exist within the academic 1. Researchers and their institutions have an ethical obli- community over the application of appropriate standards gation when conducting human research to seek to make for analyzing and reporting the results of sponsored clini- the results available publicly. cal research, especially clinical trials sponsored by indus- try. Accordingly, the AAMC, in collaboration with the 2. Contracts between sponsors and institutions for con- Centers for Education and Research in Therapeutics and ducting clinical trials should require a good faith effort to the BlueCrossBlueShield Association, has developed a set publish the results of such trials in a peer reviewed jour- of principles, recommendations, and guidelines, rooted nals in a timely fashion. in sound science and sound ethics, to guide the medical schools, teaching hospitals, and professional societies that 3. Contracts for clinical trials should contain a commit- comprise the AAMC’s membership and be broadly dis- ment of adequate funding to cover the full costs of the seminated in the professional community. Assuming that analysis defined in the protocol and the costs associated broad consensus is reached within academic medicine, with publishing the results. This principle applies even the sponsors will work to win acceptance of the principles when the study is terminated for any reason prior to by industry, the FDA and NIH, non profit meeting its pre-specified objectives. sponsors of clinical trials, patient advocacy groups, and ultimately, the entire medical community. 4. All trials meeting the ICMJE requirements2 for regis- tration should make their results publicly available, by Consensus Principles The following principles means of a link to any peer reviewed publications and should apply to all clinical trials conducted in academic by posting the results in an online accessible repository, medical institutions regardless of the source of funding. within 18 months of submission of a manuscript for pub- They encompass single site as well as multisite studies, lication. although operationalization of the principles may differ across study types and sizes. For purposes of these princi- 5. After publication of the results, the sponsor, the inves- ples, “clinical trials” should be defined by reference to the tigators, and their institutions should adopt a model for ICMJE definition: “Any research project that prospectively public sharing of the data underlying publications similar assigns human subjects to intervention and comparison to that of NIH, which permits exceptions for confidential groups to study the cause-and-effect relationship between or proprietary information. a medical intervention and a health outcome.” “Medical 34 Registration of Clinical Trials require that the sponsor of the study perform its analysis of trial data in a defined period of time. The commit- 6. Within 21 days of initiating enrollment of par- tee (or PI) should be able to conduct its own analysis ticipants, any clinical trial covered by these principles through an expert selected by it, to the extent it deems should be fully registered pursuant to the ICMJE this necessary. Whenever feasible, the expert should be requirements4 for registration. Registration must agreed upon by the P&A committee and the sponsor. include the assignment of a unique identifying number to each clinical trial. 13. The sponsor should share with the P&A committee all analyses called for by the study that the sponsor con- 7. Registration should be accomplished either in clinical- ducts of any biological materials it receives during the trials.gov or in another public, non-profit, international course of the study. registry and should include all the elements required by that registry. 14. The P&A committee or PI should make a good faith effort to disseminate the results of the study through 8. Insofar as is feasible, trial registration data should peer reviewed mechanisms. be regularly updated to include a link to all published reports associated with the study. Individual Publication Lead Investigator and Steering Committee 15. Site-specific publications in multisite trials have an unavoidable potential for bias. Because they are 9. A multisite clinical trial, at the outset, should identify almost never part of the original analytic plan, they are a lead or principal investigator and a steering committee often misleading, and should be strongly discouraged. to represent the full body of investigators. However, to respect an academic institution’s commit- ment to academic freedom, site-specific analyses should Publication and Analysis Committee nonetheless be permitted with conditions. Accordingly, an individual site investigator in a multisite trial should 10. A multisite clinical trial, at the outset, should estab- be free to analyze and publish data from the individual lish a publication and analysis committee [hereinafter site, consistent with sound principles of science and P&A committee]. It is essential that the P&A committee analysis, but only after review and comment by the P&A be independent of the sponsor’s control, have access to committee and only after publication of the study as a the full data set, understand and implement the pre- whole, or, in the absence of acceptance of the full publi- specified analysis plan, and have the resources and skills cation, within 2 years from the specified end points or both to interpret that analysis and perform additional earlier termination of the study. analysis if required. In order to prevent any appearance of undue influence by the sponsor, the P&A committee Authorship should contain a majority of participating, non-spon- sor-employed investigators, with appropriate skills in 16. Ghost or guest authorship is unacceptable. analysis and interpretation of clinical trials. The P&A Authorship implies independent, substantial, and fully committee and the steering committee may have the disclosed participation in the study and in the prepara- same membership. tion of the manuscript. It is acceptable for employees of the sponsor to participate in drafting and publication 11. The P&A committee in multisite clinical trials (or the activity, but only if their roles are fully disclosed. principal investigator of single site studies), through a qualified expert of its choosing, preferably a member of 17. Institutions conducting clinical trials should adopt that committee, should have the right to access any data as policy the standards of authorship defined by the generated during the study that the committee deems ICMJE. necessary to ensure the integrity and validity of the study and its full reporting. 18. Where applicable, investigators should use the CONSORT principles5 as guidance for publication of 12. 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Seattle Sandberg WS, Carlos R, Sandberg EH, Roizen MF. The Times, March 11-14, 2001:1-14. effect of educational gifts from pharmaceutical firms on medical students’ recall of company names of products. Acad Med, 1997;72:916-18. 39 40 Blue Ridge Academic Health Group Report Ordering Information If you would like to order copies of this publication—or any of the others listed below—please contact Janet Waidner Woodruff Health Sciences Center Emory University 1440 Clifton Road, Suite 400 Atlanta, GA 30322 Phone: 404-778-3500 Fax: 404-778-3100 blueridge@emory.edu When requesting publications, please refer to the report number and title and provide your full name, organization name, business address, city, state, zip, telephone, and email. Report 10: Managing Conflict of Interest in AHCs to Assure Healthy Industrial and Societal Relationships Report 9: Getting the Physician Right: Exceptional Health Professionalism for a New Era Report 8: Converging on Consensus? Planning the Future of Health and Health Care Report 7: Reforming Medical Education: Urgent Priority for the Academic Health Center in the New Century Report 6: Creating a Value-driven Culture and Organization in the Academic Health Center Report 5: e-Health and the Academic Health Center in a Value-driven Health Care System Report 4: In Pursuit of Great Value: Stronger Leadership in and by Academic Health Centers Report 3: Into the 21st Century: Academic Health Centers as Knowledge Leaders Report 2: Promoting Value and Expanded Coverage: Good Health Is Good Business Report 1: Academic Health Centers: Getting Down to Business 41 42