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Conflict of Interest in Medical Research, Education, and Practice 3 Policies on Conflict of Interest: Overview and Evidence Current conflict of interest policies and practices have evolved over more than four decades of increasing relationships with industry in medical education, research, and practice. The increase has been accompanied by intensifying discussions about how the risks and the expected benefits of these relationships should be evaluated and balanced. Since 1995, the U.S. Public Health Service (PHS) has required most research grantees to establish policies and procedures to ensure that the design, conduct, or reporting of research funded by PHS grants not be “biased by any conflicting financial interest of an Investigator” (42 CFR 50.601). The regulations, which are included in Appendix B, allow grantees considerable discretion in formulating policies and procedures. To provide more specific and comprehensive guidance to academic institutions on conflict of interest policies, the Association of American Medical Colleges (AAMC, 2001, 2002, 2008c), the Association of American Universities (AAU, 2001), AAMC and AAU jointly (AAMC-AAU, 2008), and the Council on Government Relations (COGR, 2002) have issued several reports with recommendations. The Federation of American Societies for Experimental Biology (FASEB) created a conflict of interest tool kit that offers extensive online resources and guidance for academic institutions, researchers, academic and professional societies, journal editors, and industry (FASEB, 2008). In 2008, the trade associations representing major pharmaceutical and medical device companies revised their codes on company interactions with health care professionals (AdvaMed, 2008; PhRMA, 2008). In addition, a number of academic medical centers, professional societies, medical journals, and other institutions have revised their policies in recent years. Criticisms of current policies and their application come from different directions. Some object that policies requiring the disclosure of financial
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Conflict of Interest in Medical Research, Education, and Practice interests can be carried too far, encouraging “readers to make ad hominem judgements” (Rothman, 2001, p. 1275) or shifting “attention away from the merits of the work and toward the biography of its author” (Jansen and Sulmasy, 2003, p. 40). Another critic describes disclosure policies as a kind of “new scientific McCarthyism” that assumes that researchers with industry ties are “tainted and untrustworthy” (Whelan, 2008, p. A19). One researcher has criticized “conflict of interest vigilantes” who “search for evidence that doctors have failed to disclose corporate connections in publications or in presentations” (Stossel, 2007, p. 59). He has also argued that continuing medical education disclosure policies mainly serve to protect bureaucrats rather than students, are based on ideology rather than evidence, and “are deeply disrespectful of physicians and researchers” (Stossel, 2008, p. 476). (See Chapter 1 for additional criticisms.) Others, however, argue that conflict of interest policies—when they exist—are often weak, inconsistent, and inadequately administered and enforced. For example, the American Medical Student Association (AMSA) assessed the conflict of interest policies of medical schools and concluded that the policies of the majority of the schools that responded either lacked important elements or were unlikely to influence behavior (AMSA, 2008b).1 Whether or not one agrees with how AMSA rated the policies, the actual texts of the policies (available at or through the AMSA website) reveal considerable variability, which is consistent with the findings of this report. Members of the U.S. Congress have strongly criticized physicians and researchers who have failed to report substantial financial relationships with industry, as they were required to do, and have proposed that pharmaceutical and medical device companies be required to report publicly their payments to physicians (see, e.g., Grassley [2008b, 2009]). Also in response to concerns about the nature of financial ties between physicians and industry and the lack of disclosure of such ties, Massachusetts enacted legislation in 2008 that requires companies to report payments to physicians, researchers, and medical societies and further provides for a marketing code of conduct 1 In AMSA’s assessment, 9 medical schools received a rating of A and 19 received a rating of B for their policies; 44 schools received a rating of F (18 for the contents of the policies that they submitted, 9 for their refusal to submit policies, and 17 for their lack of a response after repeated requests). Another 46 schools had policies under revision. (The numbers of schools are based on the ratings listed as of February 13, 2009, at http://www.amsascorecard.org/.) The project’s methodology, included the rating system, is available at http://amsascorecard.org/methodology and states that “[e]ach policy was graded by two independent assessors, blinded to the institution of origin. Any differences in scoring between the two assessors were resolved by a consensus process. The assessors received formal training in the use of the scoring system, independently evaluating and coming to a consensus on five training policies before beginning to evaluate the medical school policies.”
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Conflict of Interest in Medical Research, Education, and Practice that will prohibit or limit certain of these payments (Wallack, 2008; Lopes, 2009). This chapter outlines the basic elements of conflict of interest policies, reviews empirical data about the characteristics and consequences of those policies, and concludes with recommendations. Much of the research and descriptive information located by the committee examined the policies of academic institutions and medical journals; but the recommendations apply broadly to all institutions engaged in medical research, medical education, clinical care, or practice guideline development. The specific elements of the policies may vary according to the size, complexity, and other characteristics of different types of institutions (e.g., academic medical centers, professional societies, patient advocacy groups, and nursing homes). The focus in this chapter is on policies affecting individuals, primarily physicians and biomedical researchers (as explained in Chapter 1). Chapter 8 examines and makes recommendations about policies that govern institutional conflict of interest, which is defined to include the interests of senior institutional officials. OVERVIEW OF CONFLICT OF INTEREST POLICIES Most conflict of interest policies include the basic elements of the disclosure of financial relationships, the prohibition of certain relationships, and the management of conflicts of interest that have been identified. All of these elements are sometimes described under the general rubric of managing conflicts of interest.2 Other common elements of conflict of interest policies include definitions, specification of who is subject to the policies, enforcement provisions, and identification of which officials or units within an organization are responsible for administering and monitoring conflict of interest policies and procedures. Depending on the circumstances and the type of institution, the person responsible for reviewing initial disclosures may be a department chair, the chair of a professional society committee developing practice guidelines, the editor or deputy editor of a journal, or the chair of a continuing medical education program. When an initial review identifies a possible conflict of interest, the case may be referred to a conflict of interest committee or a more senior official for further evaluation and response. Building on Chapter 2, Box 3-1 outlines a conceptual model of the 2 PHS rules refer to procedures to “identify and manage, reduce, or eliminate conflicting interests.” Federal government policies for its employees are sometimes described in terms of the “‘three-D’ method of conflict of interest regulation, that is: disclosure, disqualification and divestiture” (Maskell, 2007, p. 3). Disqualification includes recusal from participation in a specific decision.
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Conflict of Interest in Medical Research, Education, and Practice BOX 3-1 Model of Steps Used to Identify and Respond to a Conflict of Interest Step 1 Obtain the disclosure of information about financial and other relationships that could constitute a conflict of interest. No relationships reported: stop. Relationships disclosed: go to Step 2. Step 2 Evaluate the disclosures—in light of the individual’s responsibilities or specific activities (e.g., research, teaching, and patient care)—to determine whether a conflict of interest exists. If necessary, collect additional information to assess the likelihood of undue influence and the seriousness of possible harms. No conflict exists: stop. Conflict exists: go to Step 3. Step 3 Determine whether the relationship is one prohibited under institutional or other policies or whether the risks of the relationship are so serious that the individual should either eliminate it or forgo participation in the activity put at risk by the relationship. Conflict elimination necessary: go to Step 5. Elimination not necessary: go to Step 4. Step 4 If management is appropriate, devise and implement a plan to manage the conflict. Go to Step 5. Step 5 Monitor conflict elimination or management plan and assess adherence. Plan followed. Plan not followed: go to Step 6. Step 6 Determine the nature of the noncompliance and the appropriate response (e.g., education, penalty, or revision of the plan) and implement the response. steps that institutions with a comprehensive conflict of interest policy and implementation strategy might follow when determining whether an individual has a conflict of interest and, if so, how to respond. It shows the elimination of an identified conflict of interest as an early step, although the committee’s experience suggests that the elimination of a conflicting relationship is often considered a last option. A given individual may be covered by several conflict of interest policies. For example, a medical school faculty member may have to understand and follow the policies not only of the medical school but also those of
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Conflict of Interest in Medical Research, Education, and Practice several other institutions. Depending on his or her activities, these other policies might include those of a medical journal, a provider of continuing medical education, a professional society, or a federal advisory committee. If a faculty member is engaged in research to support an application for marketing approval of a medical product by the Food and Drug Administration (FDA), the researcher can expect the study’s sponsor to ask for the disclosure of his or her financial interests related to the company and the investigational product so that the sponsor can submit the required information to the FDA (FDA, 2001). (A recent report by the Office of the Inspector General [OIG] of the U.S. Department of Health and Human Services criticized the administration of these policies and indicated that they were deficient in several respects [OIG, 2009].) Private organizations that fund research, such as the Howard Hughes Medical Institute, also may have conflict of interest policies, which they may oversee directly rather than following the practice of the National Institutes of Health (NIH) of delegating most administrative responsibility to the research institution (Cech and Leonard, 2001). In addition, the faculty of public institutions will likely be covered by state conflict of interest policies.3 The committee found few reviews or studies documenting and comparing the conflict of interest policies of institutions engaged in medical research, medical education, or clinical care. It found even less information about the implementation and effects of these policies. Most studies examine the policies of academic institutions, medical and scientific journals, or government agencies. Journal articles or news stories sometime report on individual professional societies and patient or consumer groups. In addition, through its literature review, public meetings, and other information-collecting activities, the committee identified various examples of institutional policies.4 Although these examples are not necessarily representative, they helped the committee better understand the nature of policy variability and, in some cases, the rationale for policy differences. Institutions differ considerably in the conflict of interest policy information that they make public on their websites; and even if they are available, online information is not necessarily comprehensive, clear, or current. Since the committee began work, a number of medical schools, professional societies, and other groups have announced changes in their conflict of interest 3 The state of Washington recently changed its policies on the use of certain university resources for outside work for faculty and some other university employees to “encourage the ethical transfer of technology for the economic benefit” of the state (University of Washington, 2008). 4 During the study, the committee benefited from initiatives by AMSA and the Institute on Medicine as a Profession to make medical center policies available online. These databases have been useful, although they are not complete, and many schools have indicated that they are updating their policies.
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Conflict of Interest in Medical Research, Education, and Practice policies and practices. Thus, even relatively recent overviews of conflict of interest policies may be somewhat out of date. DISCLOSURE: AN ESSENTIAL BUT INSUFFICIENT ELEMENT OF POLICY Disclosure—that is, revealing to others information that may otherwise be private or confidential—is a frequent response to concerns about conflicts of interest in various sectors of society. Disclosure by physicians and researchers to their academic or other institution is essential because institutional officials cannot evaluate and respond to individuals’ relationships with industry if they are not aware of them. Consistent with the conceptual framework outlined in Chapter 2, disclosures should provide sufficient information about the nature, scope, duration, and monetary value of relationships to allow institutions to assess the risk that secondary interests might unduly influence judgments about research, clinical care, education, or other primary interests. The committee distinguished disclosure to the physician’s or researcher’s institution from disclosure beyond the institution, for example, to patients, research participants, or the public.5 One rationale for disclosure—especially public disclosure—is the deterrence of questionable or inappropriate relationships. As Supreme Court Justice Louis Brandeis (1914) famously expressed it, “sunshine is said to be the best of disinfectants.” In a similar vein, the code of ethics of the American College of Physicians suggests that physicians considering the acceptance of gifts or other relationships with companies should ask themselves what their patients, the public, or their colleagues would think about the arrangement (Snyder and Leffler, 2005; see also Chapter 6). The Nature publishing group urges authors to avoid “any undeclared competing financial interests that could embarrass you were they to become publicly known after your work was published” (NPG, 2008). Disclosure should have beneficial consequences if it leads physicians to avoid gifts, the use of industry-controlled presentations, and other relationships that create a risk of compromising their decisions and their professional independence. It could also have harmful consequences if physicians or researchers react by avoiding relationships that promote im- 5 Some analyses refer to the provision of information to institutional officials as “reporting” and reserve the term “disclosure” for the revelation of information to members of the public (e.g., journal readers or patients) (see, e.g., AAMC ). In contrast, some policies refer to reporting of information to external groups. This report follows the common usage (including in federal policies and guidance) and applies the term “disclosure” to the provision of information to internal parties as well as to external parties.
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Conflict of Interest in Medical Research, Education, and Practice portant societal goals and that are accompanied by adequate measures to protect objective judgment. What Is Known About Disclosure Policies, Practices, and Consequences This section first reviews information about the characteristics of disclosure policies and practices. It then turns to evidence about the effectiveness of disclosure. Presence and Scope of Disclosure Requirements Medical schools The most recent comprehensive study of medical school conflict of interest policies reports on a 2003 AAMC survey of member schools (response rate of 82 percent) that was designed to characterize their policies and assess the extent to which they were consistent with the association’s 2001 recommendations on conflict of interest in clinical research (Ehringhaus and Korn, 2004).6 It found considerable variation. Almost all (95 percent) of the respondents reported that their policies covered all research involving human participants regardless of the funding source.7 Sixty-eight percent of the schools used the PHS threshold ($10,000)8 for individuals to disclose certain financial interests to the institution, whereas 27 percent reported a lower threshold. For elements not required by the PHS regulations, more than 60 percent of the respondents requested disclosure to the institution of equity in nonpublicly traded companies, regardless of the percent share (61 percent) or the estimated valuation (64 percent). The majority requested the disclosure of royalty income either above a certain threshold (38 percent) or regardless of the amount (33 percent). In addition to requiring disclosure to the institution, policies may also require that financial relationships or conflicts of interest be disclosed to individuals who might be affected by the relationship. These might include research colleagues, research participants, journal readers, students, or 6 The committee also reviewed several earlier studies for additional context and understanding of policy evolution (see, e.g., Cho et al. , Lo et al. , and McCrary et al. ). 7 In 2004, the Government Accountability Office reported that 79 percent of universities responding to their survey said that they had a single conflict of interest policy that covered all research. This is consistent with the recommendation of the AAU Task Force on Research Accountability that “all research projects at an institution, whether federally funded, funded by a non-federal entity, or funded by the institution itself, should be managed by the same conflict of interest process and treated the same” (AAU, 2001, p. 5). 8 The PHS regulations state that individuals do not need to report “salary, royalties or other payments that when aggregated for the Investigator and the Investigator’s spouse and dependent children over the next twelve months, are not expected to exceed $10,000” (NIH, 2008a, question C6, emphasis added). A similar rule applies to the disclosure of equity interests.
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Conflict of Interest in Medical Research, Education, and Practice TABLE 3-1 Percentage of Medical Schools Requiring Further Disclosures for Researchers with a Significant Financial Interest in Their Research Further Disclosure Required Percentage of Medical Schools To research participant in informed consent forms 74 To sponsors or funders of the research 65 To editors of journals to which papers or reports of research are submitted 64 In oral presentations of research results 60 In multicenter trials, to investigators, sponsors, and other institutional review boards participating in the trial 42 Other 23 SOURCE: Adapted from Ehringhaus and Korn, 2004. patients. Again, the AAMC survey showed variation in medical school policies (Table 3-1). A study by Weinfurt and colleagues (2006b) also reported on variations in disclosure policies. Forty-eight percent of medical schools had policies that mentioned the disclosure of researchers’ financial conflicts of interest to research participants. The policies varied in what information was to be disclosed. Medical and scientific journals The International Committee of Medical Journal Editors (ICMJE) has proposed Uniform Requirements for Manuscripts Submitted to Biomedical Journals that include explanations and provisions about conflicts of interest (ICMJE, 2008). The ICMJE website lists several hundred journals that follow these requirements, but the group does not verify the extent to which a journal does so. The World Association of Medical Journal Editors (WAME) has also made recommendations on conflict of interest policies (WAME, 2008). Even journals that adopt conflict of interest policies may not apply them equally to industry-funded journal supplements that present papers from a conference or collections of papers on a particular topic. These supplements are generally not peer reviewed and have been criticized for including articles of lower quality (Bero et al., 1992; Rochon et al., 1994). The National Library of Medicine will not cite and index articles from certain types of sponsored supplements unless they include specific disclosures about “any financial relationship the guest editors and authors have with the sponsoring organization and any interests that organization represents, as well as with any for-profit product discussed or implied in the supplement and/or individual articles” (NLM, 2007, unpaged). Journals may also vary their policies for review articles and editorials
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Conflict of Interest in Medical Research, Education, and Practice or may not apply their policies to review articles and editorials, which arguably offer more room for bias than original research articles. For example, a 2004 editorial in the Journal of the American College of Cardiology stated that the editors generally decline publication of review articles disclosing industry input out of concern for external influence and subtle bias (DeMaria, 2004). Editors of another journal initially declared that they would not accept review articles written by authors with conflicts of interest and then decided that it would accept such articles if the conflicts were not significant (e.g., they involved payments that were less than $10,000) (Drazen and Curfman, 2002). Two recent analyses found considerable variability in the conflict of interest policies of medical and scientific journals. Cooper and colleagues (2006b) found that 93 percent of biomedical journals reported that they had conflict of interest policies applicable to authors, 46 percent reported that they had policies applicable to reviewers, and 40 percent reported that they had policies applicable to editors. Fifty-seven percent reported that they published disclosures for all articles. Earlier studies reported that the percentage of biomedical journals with disclosure policies was lower (see, e.g., McCrary et al.  and Krimsky and Rothenberg ). Ancker and Flanagin (2007) were able to locate online conflict of interest policies for only 33 percent of 84 “high-impact, peer-reviewed” journals in 12 scientific disciplines, but a subsequent survey found that 80 percent of the 49 responding journals reported that they had policies in place. Journals vary in whether they give specific guidance to authors regarding what financial relationships or conflicts of interest must be disclosed. Ancker and Flanagin (2007) found that 68 percent of journals provided examples of conflicts of interest and 46 percent defined the term. The committee’s review of a convenience sample of journal policies revealed differences in the specificities of the policies. One journal advises simply, “[a]uthors are required to disclose any sponsorship or funding arrangements relating to their research and all authors should disclose any possible conflicts of interest” (AJN, 2008). In contrast, the New England Journal of Medicine states that disclosures are to include “all of the authors’ relationships with companies that make products studied or discussed in the article, companies that make related products, and other pertinent entities with an interest in the topic” (NEJM, 2008). Some journals ask authors about several specific types of relationships and also ask them to indicate explicitly if they have no relationships. One journal’s manuscript agreement form asks authors to certify that their manuscript has not been sponsored by a commercial entity and that if their manuscript includes no acknowledgments, it means that nonauthors have made no substantial contribution to it (AFMI, 2008).
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Conflict of Interest in Medical Research, Education, and Practice Professional societies and patient advocacy groups The committee found no published reviews of the disclosure policies of professional societies. It examined a convenience sample of professional society documents and websites and found considerable variation in the content and accessibility of those policies. (Unlike professional society codes of ethics or codes of conduct, disclosure policies do not apply to members generally but are limited to individuals holding positions of responsibility, for example, officers or members of policy-making committees.) Some societies had disclosure forms with a simple, open-ended question about relevant relationships, whereas other forms included specific categories of relationships and required that respondents either report such a relationship or check a box stating that they had none. The policies of some professional societies that develop clinical practice guidelines are discussed further in Chapter 7. The committee did not attempt to conduct a systematic review of the policies of patient advocacy and disease-specific groups. It found little information on such policies in its initial search of organizational websites and other resources. To the extent that these groups engage in activities such as the development of clinical practice guidelines or the provision of accredited continuing medical education, many of the recommendations in Chapter 7, in this chapter, and elsewhere in this report will apply. Disclosure by Companies of Payments to Physicians District of Columbia, Maine, Massachusetts, Minnesota, Vermont, and West Virginia require pharmaceutical manufacturers to report their financial relationships with physicians; and a number of other states are considering such requirements (Wallack, 2008; Lopes, 2009; MedPAC, 2009). Minnesota and Massachusetts make the information public. Vermont requires the state’s attorney general to make an annual public report based on the information that the pharmaceutical manufacturers have disclosed. Two states also require the reporting of payments by pharmaceutical manufacturers to hospitals and nursing homes. One state requires medical device companies as well as pharmaceutical companies to report payments to physicians. In general, state policies are relatively new, and their implementation and effectiveness have not been formally assessed. Some pharmaceutical and device companies have voluntarily acted to disclose publicly certain of their payments to physicians (see Chapter 6). The specific details of company plans vary and appear to be evolving as the discussion of public reporting of payments continues. Several companies have been required to make such public disclosures as a condition of settlements with the U.S. Department of Justice (Demske, 2008; see Chapter 6 for additional discussion). In 2007, bills were introduced in the U.S. Congress to establish a requirement for companies to report publicly
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Conflict of Interest in Medical Research, Education, and Practice their payments to physicians (S. 2029 and H.R. 5605, 110th Congress). As discussed in the final section of this chapter, the Medicare Payment Advisory Commission (MedPAC), which advises the Congress on a range of Medicare policy issues, has recommended a more comprehensive policy for company reporting of payments (MedPAC, 2009). Time Frame for Disclosure For employees and others who are involved with an institution for an extended period, disclosure policies generally require an initial disclosure and then periodic (e.g., yearly) disclosures as well as interim disclosures when new relationships arise or when specific events occur (e.g., the submission of a new grant proposal or an application to license intellectual property). For researchers, policies may require the disclosure of financial ties before a study begins (e.g., to university administrators and institutional review board members), during a study, (e.g., to the research team, students, or research subjects), and after the study is completed (e.g., to journal editors when papers are submitted for publication in peer-reviewed journals). The conflict of interest policies that the committee reviewed varied considerably in the time periods for which disclosure is required. Typically, policies require the disclosure of relationships that are current or that occurred during the previous year. Some policies ask about relationships that are pending, in negotiation, or expected in the next 12 months. The PHS regulations for grantees do not specify a reporting period, except that in determining whether financial relationships exceed the $10,000 threshold for reporting, researchers must consider individual and family financial relationships projected for the next 12 months. Some organizations require disclosure for periods longer than the previous year (e.g., the American Thoracic Society requires disclosure for the previous 3 years [ATS, 2008] and the Journal of the American Medical Association requires disclosure for the previous 5 years [Flanagin et al., 2006]). The requirements may vary by type of relationship. For example, the policy of the American Society of Clinical Oncology specifies disclosure within 2 years for certain relationships (e.g., honoraria and consulting arrangements) but not for others (e.g., research funding) (ASCO, 2007). Administrative Burden of Disclosure Policies Disclosure to multiple organizations with various policies can clearly be burdensome for individuals who have received multiple grants, write many papers, serve on various committees and advisory panels, and make many continuing medical education presentations. The committee found little em-
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Conflict of Interest in Medical Research, Education, and Practice Policy Dissemination and Education Strategies AAMC has advised academic medical centers to provide education and training about their conflict of interest policies to all faculty, staff, students, and trainees (AAMC, 2001). In 2002, NIH reported that the policies of some research institutions were difficult to locate and were sometimes interspersed in various other institutional policies on issues such as ethics, purchasing, and consulting. It recommended that institutions present their conflict of interest policy “as a complete, self-contained document with citations and web links to supporting policies, procedures, and Federal and state regulations, as appropriate” (NIH, 2002, unpaged). The Office of Extramural Research at NIH recently created an online tutorial on conflict of interest and other materials intended to help investigators understand and comply with NIH policies (the tutorial is available at http://grants.nih.gov/grants/policy/coi/). The IOM committee’s review of the policies and other information on conflict of interest from academic medical centers and universities showed that they vary considerably in the informational resources that they make available to their faculty and staff. Some schools provide online resources that are intended to help people easily find relevant institutional policies and resources (including individuals who can answer questions about the policies). Examples include the University of Minnesota, which has a web-based training module on conflict of interest (University of Minnesota, 2008), and Stanford University, which has frequently asked question units on conflict of interest and related university policies, as well as a quiz and other resources (Stanford University, undated). A professional society may publicize its policies by publishing them in the society’s journal(s). It may also make the policies accessible to the public on its website. Compliance and Enforcement The earlier discussion of compliance with and the enforcement of disclosure policies reviewed information about compliance with and the enforcement of policies as they apply to individuals. The discussion in this section focuses on the extent to which research institutions follow applicable PHS rules. A 2002 review of a sample of grantee policies undertaken by the NIH Office of Extramural Research found that institutional policies often did not reflect the requirements of the PHS regulations (NIH, 2002). In 2007, NIH reported on 18 targeted site reviews regarding grantee compliance with PHS conflict of interest policies. It found no instances of intentional noncompliance and concluded that the institutions that it visited generally
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Conflict of Interest in Medical Research, Education, and Practice had “implemented the Federal regulation thoughtfully and with diligence” (NIH, 2007). It did, however, report some problems with timely and consistent reporting and suggested the need for improvements in several areas, including educational and enforcement procedures, the clarity of the forms used to report conflicts of interest, and definitions. A 2008 report by the OIG of the U.S. Department of Health and Human Services criticized NIH’s oversight of grantee institutions (OIG, 2008). Although NIH accepted some of the report’s suggestions, it rejected taking a more active oversight role, particularly requiring and reviewing detailed conflict of interest reports from institutions. Doing so would “effectively, if not legally, transfer the locus of responsibility for managing [financial conflicts of interest] from the grantee institution to the Federal Government” (Zerhouni  in OIG [2008, pp. 20–21]). The OIG disagreed that collection of the information would usurp grantee responsibilities, and it argued that without some details about the nature (and not just the existence) of the conflicts that were identified, NIH lacks important information that it needs to oversee and enforce PHS regulations. Also in 2008, NIH announced the development of and began testing an electronic reporting and tracking tool that that would allow grantee institutions to prepare and submit required conflict of interest reports and search past reports. Consistent with one of the OIG report’s recommendations, the tool would also provide a central web-based location for grantee conflict of interest reports received across NIH (Bravo, 2008; see also NIH [2008b]). In addition, NIH has initiated procedures and training to ensure proper NIH staff oversight of conflict of interest issues involving grantees. The IOM committee identified some publicly reported instances of NIH enforcement of PHS policies. For example, in October 2008, after congressional inquiries and reports of apparent major inaccuracies in a researcher’s financial disclosures to Emory University, NIH suspended a $9 million grant for a study led by the researcher and instituted special conditions for the institution’s other studies conducted with the support of NIH grants (Harris, 2008; Kaiser, 2008). Subsequently, the university removed the individual from his post as department chair and significantly restricted his outside activities (Shelton, 2008). RECOMMENDATIONS Empirical data on conflict of interest policies are limited, have methodological shortcomings, and tend to focus on academic institutions. Some institutions do not make their policies easily accessible. Institutions also revise their policies, which limits the usefulness of older studies. Nonetheless, the available evidence points to substantial variations in institutional requirements for the disclosure of financial relationships or conflicts of interest.
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Conflict of Interest in Medical Research, Education, and Practice Variations exist in who is required to report on a conflict of interest, when reporting is required, and what relationships and what details about these relationships are to be reported (e.g., the exact amounts of payments rather than payments above a threshold or within dollar categories). Variations also exist in what relationships are prohibited, what criteria are considered in evaluating financial relationships, what strategies are employed when a conflict of interest is identified, and what is done to monitor and promote adherence to policies. These extensive variations raise concerns that some institutions may not have sufficient data to make determinations about the extent and the nature of an individual’s financial relationships or to judge the severity of a conflict of interest. Some institutions may also lack adequate procedures for evaluating and eliminating or managing identified conflicts. The committee expects that there are many explanations for the variations in policies, including the press of other issues demanding attention, a reluctance to propose changes that may spark controversy and dissension, and cultural traditions that vary in how restrictions on the pursuit of personal gain are viewed. Absent outside pressures and oversight, variation in conflict of interest policies may encourage an unhealthy competition among institutions to adopt weak policies and shirk enforcement. It may also aid investigators who want to avoid restrictions on their pursuit of secondary financial interests. The recommendations presented in this chapter and in this report are intended to discourage such undesirable institutional and individual behavior but not to damage beneficial collaborations. If institutions do not act voluntarily to strengthen their conflict of interest policies, such inaction may prompt government regulation. (The recommendations below focus on individual conflicts of interest. Chapter 8 presents recommendations on conflicts of interest at the institutional level.) Adopting Conflict of Interest Policies The committee’s first recommendation deals with institutional basics: the adoption of a policy and the creation of a conflict of interest committee. The details of the policies may vary, depending on an institution’s mission and other characteristics, but certain features are fundamental to credible and meaningful conflict of interest policies. RECOMMENDATION 3.1 Institutions that carry out medical research, medical education, clinical care, or practice guideline development should adopt, implement, and make public conflict of interest policies for individuals that are consistent with the other recommendations in this report. To manage identified conflicts of interest and to
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Conflict of Interest in Medical Research, Education, and Practice monitor the implementation of management recommendations, institutions should create a conflict of interest committee. That committee should use a full range of management tools, as appropriate, including elimination of the conflicting financial interest, prohibition or restriction of involvement of the individual with a conflict of interest in the activity related to the conflict, and providing additional disclosures of the conflict of interest. Recommendation 3.1 calls on all institutions that conduct medical research, offer medical education, provide clinical care, or develop practice guidelines to adopt comprehensive conflict of interest policies for their employees. These policies should cover all those whose decisions and judgments affect their institution’s missions and primary interests. Consistent with the committee’s charge, the recommendation refers only to relationships with pharmaceutical, medical device, and biotechnology companies. In practice, individual institutions will design their policies to cover other relevant relationships. These might include consulting or speaking arrangements with health insurance companies, leadership positions with professional organizations, teaching at other institutions, and service on government advisory committees. (As described in Chapter 2, some of these relationships may present conflicts of commitment.) So that those who rely on academic medical centers, medical journals, professional societies, patient advocacy groups, and other institutions may assess an institution’s conflict of interest policies, the policies should be publicly available, for example, on the institution’s website. Although the details will vary, it is also important for institutions to disseminate and explain their policies to those who are subject to them. Strategies might include the provision of an education module and the inclusion of a set of frequently asked questions. Recommendation 3.1 also calls on academic medical centers and other institutions to create conflict of interest committees to manage conflicts of interest involving individuals. This reiterates a recommendation of AAMC, which found in its 2003 survey that not all medical schools reported that they had such committees. Professional societies and other institutions would also benefit from conflict of interest committees that would implement their policies. For example, a conflict of interest committee for a professional society would review conflicts that arise in different aspects of the society’s work, including the development of clinical practice guidelines and the conduct of society meetings and educational programs. (For some very small institutions, the formation of a formal committee may not be necessary if the relevant responsibilities are clearly defined and assigned to appropriate staff or, possibly, volunteers.) A conflict of interest committee should bring experience and consistency to evaluations of financial relation-
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Conflict of Interest in Medical Research, Education, and Practice ships with industry and decisions about those relationships, although the specific details (e.g., how risks and potential benefits are assessed and what management options are considered) may vary, depending on the activity in question. The recommendation mentions monitoring as an activity of the conflict of interest committee, but in practice, the details of monitoring may best be handled by an administrative unit, with the conflict of interest committee providing more general oversight. Improving Information for Identifying and Evaluating Conflicts of Interest Disclosure as an Element of Policy The disclosure of financial relationships with industry is only one part of a comprehensive conflict of interest policy, but it is nonetheless an essential step. Unless institutions know about these relationships, they cannot assess them and determine whether additional steps—such as the elimination or management of a relationship—are necessary. Recommendation 3.2 identifies key features of policies on disclosure. Recommendations in Chapters 4, 5, 6, and 7 provide guidance about the elimination or management of conflicts of interest in the contexts of medical research and education, patient care, and practice guideline development, respectively. RECOMMENDATION 3.2 As part of their conflict of interest policies, institutions should require individuals covered by their policies, including senior institutional officials, to disclose financial relationships with pharmaceutical, medical device, and biotechnology companies to the institution on an annual basis and when an individual’s situation changes significantly. The policies should request disclosures that are sufficiently specific and comprehensive (with no minimum dollar threshold) to allow others to assess the severity of the conflicts; avoid unnecessary administrative burdens on individuals making disclosures; and require further disclosure, as appropriate, for example, to the conflict of interest committee, the institutional review board, and the contracts and grants office. Conflict of interest policies should cover individuals who have discretion in the conduct of research and educational activities, the provision of clinical care, and the development of clinical practice guidelines. (Senior officials are also covered by Recommendation 8.1 in Chapter 8, which examines institutional conflicts of interest.) Disclosures should be made
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Conflict of Interest in Medical Research, Education, and Practice at least annually and more often if an individual’s situation changes. They should also be updated during the year if an individual’s situation changes significantly, for example, because an existing relationship expands (e.g., a faculty member who is a company consultant is also appointed to the company’s governing board) or because a new relationship (e.g., a new consulting arrangement) is created that is relevant to a specific activity (e.g., participation in a panel developing a clinical practice guideline). In addition to requiring disclosure of conflicts of interest to the institutional review board and the other entities listed in the recommendation, policies may also cover additional disclosures, for example, to entities responsible for continuing medical education program oversight. Elements of a disclosure policy may vary depending on the institution, but the disclosures should be sufficiently specific to support the identification of conflicts of interest and an evaluation of their severity. For example, if information on the dollar value of relationships is reported in categories rather than specific amounts, the highest categories should reach into the hundreds of thousands of dollars. The committee recommends the elimination of minimum thresholds for individual reporting of financial relationships. As discussed earlier in this chapter, the 1995 PHS regulations specify a $10,000 threshold, which applies to the individual and his or her spouse and dependent children. Most PHS grantees have adopted this threshold, although approximately one-quarter require reporting regardless of the dollar value of the relationship. The committee recognizes that elimination of the minimum threshold would add to the burden both for those reporting and for those reviewing relationships but believes that it is important to increase the accuracy of reporting and provide institutions with a more complete picture of an individual’s financial relationships across different reporting categories (e.g., consulting, advisory committee service, and speaking). The committee also notes research that suggests that even small payments may put an individual at risk of unconscious bias. In their joint report on conflict of interest in human subjects research, AAMC and AAU also recommended removing minimum (de minimis) thresholds (AAMC-AAU, 2008). NIH should seek revisions in the PHS regulations to eliminate the threshold, but NIH grantees should act without waiting for such revisions. Greater Consistency in Disclosure Policies The committee recognizes that the objective of achieving sufficient specificity in disclosures may sometimes be in tension with the objective of minimizing the administrative burdens of disclosure. To the extent that the consensus process proposed in Recommendation 3.3 is successful, it may help resolve these tensions by promoting greater consistency across institutions. Greater consistency should simplify the demands on those who
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Conflict of Interest in Medical Research, Education, and Practice must understand and comply with the disclosure requirements of multiple institutions. RECOMMENDATION 3.3 National organizations that represent academic medical centers, other health care providers, and physicians and researchers should convene a broad-based consensus development process to establish a standard content, a standard format, and standard procedures for the disclosure of financial relationships with industry. To achieve greater consistency in institutional disclosure requirements, Recommendation 3.1 calls for a broad-based national consensus development process. This undertaking would be convened by national organizations representing academic medical centers, other health care providers, physicians, and researchers and would also include representatives of professional societies; consumer and patient advocacy groups; accreditation, certification, and licensing agencies; medical journals and organizations of medical journal editors; health plans and insurers; government agencies, including NIH and the FDA; and organizations with expertise in database development and management. The process used by AAMC to develop its recent recommendations on relationships with industry in medical education offers one model for the process, although the task would be narrower and more detailed in its focus on definitions of the financial relationships to be disclosed, reporting formats, and similar matters. The committee appreciates that different disclosures may be required for different purposes. For example, the information that a medical journal needs from the authors of a manuscript differs from the information that a government agency may require for members of an advisory panel. For similar institutions (e.g., for medical journals as a category and for similar government advisory panels as a category), the objective would be to develop a consensus on a common format. A major task for the consensus development process would be to agree on the categories of relationships that need to be disclosed and the type of information about each relationship that is needed to evaluate it. Consulting is an example of a category that needs further specification. That term can cover relationships that range from the provision of promotional or marketing support to a company to the offering of objective technical advice on scientific advances, products in development, or research study design. The institution of standard categories, definitions, and similar agreements should reduce confusion, misunderstandings, and misinterpretations. In technical terms, the task for the consensus group would be to specify the elements for a relational database, including the definitions and attributes of these elements. Once the elements are specified, the expectation is that software developers would create programs that physicians and
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Conflict of Interest in Medical Research, Education, and Practice TABLE 3-3 Candidate List of Categories of Financial Relationships with Industry to Be Disclosed Research grants and contracts Consulting agreements Participation in speakers bureaus Honoraria Intellectual property, including patents, royalties, licensing fees Stock, options, warrants, and other ownership (excepting general mutual funds) Position with a company Company governing boards Technical advisory committees, scientific advisory boards, and marketing panels Company employee or officer, full or part time Authorship of publications prepared by others Expert witness for a plaintiff or a defendant Other payments or financial relationships researchers could use on their computers to enter, store, and update information on their financial relationships. The software would then format the information as needed for disclosures for various purposes (e.g., submission to an academic medical center or a medical journal). It would be similar to reference software that allows authors to format references to meet the specifications of different journals. As a starting point, Table 3-3 presents a candidate list of basic categories of the relationships to be disclosed. Each requires further definitions, and some might require subcategories. The committee did not propose a specific format for the provision of information about these relationships. It is important, however, that any format promote completeness and specificity, for example, by requiring individuals to check one box if they have a particular relationship, to check another box to declare explicitly that they do not have the relationship, and to provide certain details about an indicated relationship (e.g., its value, the company involved, and the nature of the work). In addition to the categories of relationships to be disclosed, the consensus process needs to address several other key questions. For example, what details of relationships need to be reported (e.g., the amount of income and the name of the company)? How should amounts be reported? Would it be preferable to have individuals making disclosures check a box indicating the range of income from a relationship or should they provide specific dollar amounts? Will a single time frame (e.g., the relationships in existence during the previous 12 months) be adequate for all purposes? How should the financial relationships of close family members (e.g., spouses or domestic partners, dependent children, and parents) be considered?
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Conflict of Interest in Medical Research, Education, and Practice Company Reporting of Payments to Individuals and Institutions Recommendations 3.2 and 3.3 involve disclosures by individuals to organizations. The next recommendation proposes requirements for companies. Several state laws and proposals for additional state or federal rules reflect concerns about inaccurate and incomplete disclosures. As discussed earlier, these laws and proposals vary, for example, in the types of companies and payments or relationships that they cover and in provisions for public reporting. In response to proposals for additional state and national legislation, several industry groups and individual companies have supported some form of company disclosure while seeking to minimize the administrative burdens of such reporting and to protect information that might reveal business strategies to competitors (Finance Committee, U.S. Senate, 2008). Recommendation 3.4 calls for a broad national reporting program. RECOMMENDATION 3.4 The U.S. Congress should create a national program that requires pharmaceutical, medical device, and biotechnology companies and their foundations to publicly report payments to physicians and other prescribers, biomedical researchers, health care institutions, professional societies, patient advocacy and disease-specific groups, providers of continuing medical education, and foundations created by any of these entities. Until the Congress acts, companies should voluntarily adopt such reporting. A national law covering company payments to physicians, researchers, and medical institutions would be a useful supplement to policies that require individual physicians, researchers, and others to disclose financial relationships to institutions. It should provide that company-reported payments be readily available on a searchable public website that allows the aggregation of all payments made to an individual or organization, although some personal identifying information might be restricted to protect individuals against, for example, identity theft. Such a database could help institutions and potentially others to monitor adherence to institutional disclosure policies. It would not substitute for institutional conflict of interest policies. It also would not eliminate conflicts of interest. One objective of drafting and implementing legislation and explaining it to the public and those affected would be to discourage the inference that all reported relationships are bad and to avoid harm to constructive collaborations. The committee did not investigate program options and administration in detail, but it generally supports the approach to company reporting discussed by MedPAC during several public sessions in 2008 and presented in MedPAC’s March 2009 report (MedPAC, 2008a,b,c,d, 2009). Consistent
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Conflict of Interest in Medical Research, Education, and Practice with the committee’s recommendation but in contrast to state policies and some other proposals for federal policy, MedPAC’s proposal covers not only payments to physicians but also payments to a range of organizations, including medical schools, professional societies, and providers of continuing medical education. The committee’s proposal would add payments to biomedical researchers. The MedPAC recommendation would add payments to pharmacies and pharmacists, health plans, and pharmacy benefit managers as well as payments by medical supply companies. Companies could include clarifying details about the context of a payment (e.g., specifying whether the payment is a research grant that covers all project costs and not just the investigator’s salary). The committee considers these to be reasonable provisions for a company reporting program. Implementing regulations would need to specify clear definitions and exact categories for the reporting of payments. The consensus-building activity proposed in Recommendation 3.3 could contribute to this specification and promote consistency with institutional disclosure policies. As proposed by MedPAC, the database of company-reported information would be public, but the physician’s National Provider Identifier (NPI) would not be given.18 The entire database would be available to researchers who enter into confidentiality and data use agreements with the secretary of the U.S. Department of Health and Human Services. The database would be searchable by manufacturer; recipient name, location, and specialty (if applicable); type of payment; name of related product (if applicable); and year. The MedPAC report did not include an estimate of the costs to the government of creating and maintaining the systems but notes that the costs would be higher than those of state systems, only one of which makes the data public, but not in a searchable database. In MedPAC’s proposal, company reporting would be required annually, but reporting for a clinical trial could be delayed until the trial was publicly registered or until FDA approval related to the development of a new product was granted (but not later than 2 years after the payments were made). The national policy would preempt state policies, to the extent that they cover the same categories of payments and recipients, and would provide for civil penalties for noncompliance. Legislation introduced in the U.S. Congress in 2009 includes similar provisions on these points (Grassley, 2009). In addition to the proposal on company reporting, MedPAC has also proposed that the Congress require hospitals and other providers to report (and the government to post on a public website) on physicians’ direct 18 The NPI is a unique number mandated by the U.S. government for most U.S. physicians that is available in a publicly accessible database that links it to the physician’s name, practice location, business office location, license numbers, and other identifiers.
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Conflict of Interest in Medical Research, Education, and Practice or indirect ownership shares in the facility (MedPAC, 2009; see further discussion in Chapter 6). The provision of recommendations on conflicts of interest arising from physician ownership of facilities was outside this committee’s charge. The reporting program proposed by MedPAC would make considerable additional information available to researchers, patients, and others. A discussion of the pros and cons of establishing a broader system of disclosure is presented in Appendix F. Recommendations in the Following Chapters The recommendations in this chapter call for institutions to adopt conflict of interest policies consistent with the recommendations in this report and for individual and cooperative institutional efforts and legislative actions to strengthen policies on the disclosure of individual and institutional financial relationships with industry. The next four chapters of this report offer additional recommendations related to policies and practices in the specific areas of medical research, medical education, patient care, and the development of clinical practice guidelines. Chapter 4 calls for institutions to generally bar researchers with a conflict of interest from conducting research with human participants except when the investigator’s expertise is essential to the safe and rigorous conduct of the research. Chapters 5 and 6, among other recommendations, call for physicians and researchers to forgo and institutions to prohibit or end certain relationships with industry that present unacceptable risks of undue influence over professional decision making or a loss of public trust. Chapter 7 includes recommendations for reducing industry influence in the development of clinical practice guidelines and increasing the levels of disclosure of organizational and individual financial relationships. Chapter 8 recommends that institutions establish policies at the board level to identify, limit, and manage institution-level conflicts of interest. The final chapter calls for a range of organizations to develop incentives to promote the institutional adoption and implementation of the policies recommended here. It also calls for the development of a research agenda to evaluate and guide improvements in conflict of interest policies and procedures.