A problem of unheralded proportions
Psychiatry—and academic psychiatry in particular—is facing a credibility problem of unheralded proportions that is being played out publicly in the pages of ‘The New York Times’ and ‘The Wall Street Journal’ and in the US House of Congress.
The issue is the relationship between psychiatry and the pharmaceutical industry. While the spotlight of public disapprobation has focused upon a small number of leading figures, it is an issue for all psychiatrists. Furthermore, though certainly an issue for the entire medical profession, it would appear that psychiatry has become particularly enmeshed, despite claims of an unreasonable focus on this discipline.
The stakes are high. Psychiatry has always been on tenuous scientific ground because of the limited understanding of the aetiological processes underlying mental illnesses, leading to debates over theories and therapies that are often based largely on polemic rather than reason or evidence. It has been vulnerable to the influential, persuasive, and mellifluous voices—be they of pharmacological or psychological bent. For a discipline whose repute has been under attack from various quarters, it is essential that it gets its house in order—not only for the sake of patients and their families, but also for the credibility of the profession. This is a timely wake-up call for psychiatry worldwide (Freedman et al. 2009).
Public and media concern about this relationship
The recent highly publicized ‘outing’ of the details of the relationship between medical practitioners and the pharmaceutical industry has largely arisen from two sources: US Senator Charles Grassley (Republican of Iowa), and a series of articles in the medical press, particularly the British Medical Journal and Nature, with frequent communications by the Australian medical journalist Ray Moynihan (amongst others).
Grassley’s senatorial enquiries have claimed exorbitant and opaque relations between some senior US psychiatrists and industry. Some of the high-profile clinicians implicated include Charles Nemeroff of Emory University (Harris 2008b, a; Wadman2008), Joseph Biederman of Harvard (Editorial 2008; Biederman, 2008), Frederick Goodwin (Harris 2008a), and Alan Schatzberg, the president-elect of the American Psychiatric Association (Carey and Harris 2009). The allegations against Nemeroff and Biederman relate to failure to accurately disclose to their respective universities their amount of earnings from the pharmaceutical industry; the allegations against Nemeroff have led to his standing down as Chair of the Department of Psychiatry at Emory. The allegation against Goodwin related to transparency of disclosure of industry funding for programmes on his US radio show ‘The Infinite Mind’. For Schatzberg, the issue has been transparency over his financial holdings in a company that has developed a therapeutic compound upon which he has researched and reported.
In March 2008, Grassley and another US Senator (Kohn) introduced the ‘Grassley-Kohn Physician Payments Sunshine Act of 2008’ to mandate disclosure of remuneration to doctors. This has yet to be passed. It should be noted though, that such disclosure is already legislated in the US states of Maine, Minnesota, Vermont, and West Virginia.
Ray Moynihan is a journalist who had worked with the Australian Broadcasting Commission where he initiated investigative reporting into the relationship between the medical profession and the pharmaceutical industry. Receiving a Harkness Fellowship to pursue this line of work based at Harvard, Moynihan has published both formal research (Moynihan et al. 2000; Moynihan and Sweet 2000) and commentaries (Moynihan 2003a; Moynihan et al. 2000) on this topic. In late 2008, he was interviewed on this matter in Nature Neuroscience (Bjorn 2008). One of Moynihan’s areas of focus has been on ‘disease mongering’, i.e., the creation of new poorly-defined concepts of illness that are in the commercial interests of industry. Furthermore, he was a key player in recent legal action in Australia which compelled the pharmaceutical industry in that country to register on-line details of all pharmaceutical industry sponsored educational events (<http://www.medicinesaustralia.com.au/pages/page136.as>). Other targets for Moynihan have included industry sponsorship of professional scientific meetings such as that of the Royal Australian and New Zealand College of Psychiatrists (Moynihan 2008a), and the ‘independence’ of so-called ‘opinion leaders’ (Moynihan 2008b).
Institutional concern: The example of the National Institutes of Health
Even prior to the Grassley inquiries, there had been major concerns at the US National Institutes of Health (NIH). In the most highly publicized individual case (Bhattacharjee 2007), Trey Sunderland, once chief of the geriatric psychiatry branch at the National Institute of Mental Health in Bethesda, Maryland, was found guilty of failing to report more than US$600,000 in consulting fees from Pfizer while providing spinal fluid samples to the company for Alzheimer’s studies. In late 2006, he was convicted of violating US federal conflict-of-interest laws and sentenced to two years of probation, 400 hours of community service, and an obligation to repay US$300,000 of his earnings. The broader concern at NIH led to a formal Conflict-of-Interest Inquiry being instigated by the NIH Director Elias Zerhouni, which found that 44 current and former employees had violated conflict-of-interest rules (Steinbrook 2004; Weiss, 2005). This inquiry resulted in changes in NIH rules related to financial interests in pharmaceutical companies, with senior NIH staff being required to divest all stocks in relevant companies, and (for all staff) a blanket prohibition on both consulting and other activities with medical and pharmaceutical companies (Hooper 2005).
Aims of this chapter
This chapter will explore the nature of, and reasons for, the growing aberrations in this relationship, focusing both on the broader relationship between medicine and the pharmaceutical industry, and on the relationship with psychiatry in particular. It will examine recent proposals—from academia, professional bodies, and the pharmaceutical industry itself—for ‘normalizing’ and regulating this relationship. This chapter will work to the premise that it is not the relationship per se that is the problem, but how that is enacted at both high and low levels within psychiatry. Whilst some argue that the medical community should divorce itself completely from industry, this is unrealistic. Very few effective compounds have been developed without private industry. Even the introduction of lithium into clinical practice required the expertise of private industry to finally gain FDA approval (Johnson and Gershon 1999). There is no doubting, however, that the relationship between the medical profession and industry is currently dysfunctional. The challenge is how this association can become one based on integrity and transparency.
The nature of the relationship between the medical profession and the pharmaceutical industry
There are few, if any, analogies for the relationship between the medical profession and the pharmaceutical industry. Industry develops medicines to be used by patients, but (in most cases) is unable to directly advertise or sell to these patients, rather marketing via ‘intermediaries’—the doctors who prescribe and the pharmacists who dispense.
Moynihan (2003a, b) provides the analogy of: ‘Twisted together like the snake and the staff, doctors and drug companies have become entangled in a web of interactions as controversial as they are ubiquitous’. He argues forcefully for recognition of such ‘entanglement’ and the imperative for ‘disentanglement’. Somewhat more extreme and polemical, the UK academic psychiatrist Moncrieff (2006) has argued in ideological terms. She contends that the ‘politics of neoliberalism’ underlie the drive to formulate anxiety and inadequacy in terms of disrupted biochemistry requiring psychotropic therapies, thereby driving individuals to become more accepting of ‘pressured working conditions’ and more likely to ‘inhibit social and political responses’.
However, as thoughtfully discussed by Komesaroff (Komesaroff and Kerridge 2002): ‘medical practitioners and the pharmaceutical industry serve interests that sometimes overlap and sometimes conflict’. In other words, there are substantial (in their terms) ‘dualities of interests’ between the profession and industry, as well as the potential for major conflict of interests, which have led to the current parlous situation.
There is a critical need to develop guidelines for developing a healthy adult relationship between the profession and industry. The major ‘duality of interest’ is the need to develop improved treatments that will reduce morbidity and mortality rates for the many medical conditions for which current therapies are either inadequate or non-existent. The challenge is how to do this without compromising the integrity of the professional bodies themselves (Moynihan et al. 2008).
General literature on the relationship of doctors to industry
Contact between the medical profession and the pharmaceutical industry is extensive (Blumenthal 2004). In the US, Campbell et al. (2007) reported on doctor–industry relationships in a survey of 1,662 physicians conducted by the Institute of Medicine as a Profession (IMAP). Most physicians (94 per cent) reported some type of relationship with industry, most commonly receiving food in the workplace or drug samples. More than one third received reimbursement for costs associated with professional meetings or continuing medical education (CME), while more than one quarter received payments for consulting, giving lectures, or enrolling patients in trials. Cardiologists were much more likely to receive payments than family practitioners.
In a highly-cited review of studies on the relationship between the pharmaceutical industry and the medical professional (subtitled ‘Is a gift ever a gift?’), Wazana (2000) examined all relevant publications that had been published since 1993, identifying 29 suitable data-based reports. These studies found that physicians generally endorsed the propriety of having relationships with industry. Such contacts usually began during medical school, and continued at a rate of about four times per month. Wazana found that having meetings with pharmaceutical representatives was significantly associated with both requests from physicians for adding drugs to hospital formularies, and to changes in their own prescribing practice. Drug company-sponsored CME activities preferentially highlighted the sponsor’s products compared to other CME programmes. Attending sponsored CME events and accepting funding for travel or lodging for educational symposia was associated with increased prescription rates of the sponsor’s medication. Attending presentations given by pharmaceutical representative speakers was also associated with such prescribing. Wazana recommended that this clear evidence of the impact of such contacts on prescribing and professional behaviour needed to be addressed at the level of policy and education.
In the same year as Wazana’s review, Angell (2000) wrote an editorial in the New England Journal of Medicine, raising major concerns about the growing links of academia with industry. She commented: ‘Academic institutions and their clinical faculty members must take care not to be open to the charge that they are for sale’. Further, in an aside of pertinence to this current chapter focusing on psychiatry, she stated: ‘ … as we spoke with research psychiatrists about writing an editorial on the treatment of depression, we found very few who did not have financial ties to drug companies that make antidepressants’.
Research on the various types of clinician relationships with industry
In the only qualitative study of this relationship, Doran et al. (2006) reported on the outcome of in-depth interviews with 50 Australian medical specialists. The authors categorized medical specialists into three types: confident engagers, ambivalent engagers, and avoiders. ‘Confident engagers’ (the majority of those interviewed) described themselves as engaging with industry in the belief that the relationship between themselves and the pharmaceutical industry was essentially sound and beneficial and could be effectively managed to maintain benefits to both parties. ‘Ambivalent engagers’ (the next largest group) included specialists who described engaging with industry but felt uneasy in this engagement. They described an interaction coloured by wariness of having their autonomy compromised and creating a conflict of interest. ‘Avoiders’ (the minority) described a tendency to avoid contact with industry as much as possible, though they found this difficult in light of the proliferation of industry promotional objects and advertisements.
Specific ‘points of contact’ between the profession and industry
‘Gifts’ may vary from the simple (pens, pads, or cheap meals such as pizza), to provision of educational books and equipment (such as stethoscopes or weighing machines), to tickets for sporting or cultural events, through to sponsorship to attend major national or international meetings (usually involving at least business-class travel and accommodation at five-star hotels). As reviewed by Wazana (2000), meals are more an issue for junior staff, whereas sponsorship to attend meetings or payment for speaking at industry-sponsored events (honoraria) is more likely to be offered to specialists. Furthermore, such offers to consultants are more likely to be given to those with research links to industry, or to those on industry advisory panels.
In one of the few studies to document the extent and nature of the giving and receipt of gifts, McNeill et al. (2006) surveyed 823 Australian medical specialists. They found that a high proportion of specialists received offers of food (96 per cent), items for the office (94 per cent), personal gifts (51 per cent) and journals or textbooks (50 per cent). Most were invited to product launches, symposia, or educational events (75–84 per cent) and 52 per cent received offers of travel to conferences. A high proportion of offers were accepted (over 65 per cent), excepting for lower acceptance rates for invitations to product launches (49 per cent), sponsored symposia (53%), and offers of travel including partners (27 per cent). Fifteen percent of specialists had requested financial support, for example to attend conferences. Most gifts and requests complied with national professional and industry guidelines, but some did not, including personal gifts, tickets to sporting events, entertainment, and travel expenses for partners.
Brennan et al. (2006) in a broad discussion on the relationship between industry and US academic centres, emphasized the impact of receipt of even small gifts. Drawing from social science research (Dana and Loewenstein 2003), he commented on the general human impulse to ‘reciprocate’ for even small gifts, and that those receiving such gifts are often unable to remain objective as they ‘reweigh information and choices in light of the gift’. Further, he stated that ‘… the expectation of reciprocity may be the primary motive for gift-giving’. In the Taskforce Report of the Association of American Medical Colleges in 2008 (AAMC 2008) this issue is expanded upon: ‘Thus, although strong motivation and altruistic intent exist in most physician-industry interactions, the interaction may be unwittingly undermined when innate reciprocity mechanisms are engaged’.
Key opinion / thought leaders
Key opinion leaders are senior doctors (usually academics) whose opinions are considered influential in determining both diagnostic and therapeutic practice. As quoted by a retired industry sales representative in a confronting commentary by Moynihan (2008b): ‘Key opinion leaders were salespeople for us, and we would routinely measure the return on our investment, by tracking prescriptions before and after their presentations’. Undoubtedly, significant resources are lavished on this group, and those targeted by Grassley’s inquiries would be considered within this category. This has led to calls for public disclosure of earnings received from industry, a call currently not headed by professional guidelines, but ironically a call that recently has been acceded to by industry itself, with Eli Lilly, GSK, Merck, and Pfizer promising in late 2008 and early 2009 to disclose all remuneration to medical practitioners. Healy (2006) has also discussed the potential influential role of such opinion leaders in the development of so-called ‘independent’ clinical practice guidelines.
Moynihan et al. (2000) have found that in media reports on new medications in which an expert was cited, 50 per cent of such experts had financial ties to industry, and in only one-third of these cases were those ties acknowledged. This blurring of roles by some opinion leaders (in Moynihan’s provocative terms, ‘Independent experts or drug representatives in disguise?’ (Moynihan et al. 2008)) coincides with reduced budgets for quality health journalism by many media outlets, meaning less scrutiny by journalists of press releases from industry and their associated public relations companies. Furthermore, there have been calls for registries of ‘untied’ experts and the publication of such a list in the BMJ (Lenzer and Brownlee 2008). The interested reader is referred to the BMJ ‘Head to Head’ commentary on the pros and cons of the industry utilization of key opinion leaders (Buckwell 2008). These disturbing revelations highlight the need for senior clinicians to be transparent about any potential conflicts of interest in media releases or in contributions to clinical practice guidelines.
Advisory boards / speakers bureaux
Industry advisory boards may be national or international. Little has been written about these, as they are somewhat opaque to the outside world. While ostensibly established to provide independent scientific advice to industry, they vary enormously in actual practice. In my own experience, many do act with integrity and professional independence, providing helpful ‘sounding boards’ to industry, even to the point of frank and skeptical responses to in-house industry research or marketing programmes. Others are almost obsequious in their relationship with the companies, focusing largely on marketing strategies and the provision of ‘friendly’ speakers for new product launches—be they speaking on specific products or on relevant clinical issues—thereby providing ‘academic credibility’ to the company and product.
There has been considerable recent debate about the acceptability of company speaker bureaux, with the Association of American Medical Colleges (AAMC 2008) recently proscribing this practice for US academics—a stance not accepted by a number of industry representatives on that guideline panel. While many speakers use such opportunities for quality product-independent continuing education, others are less scrupulous, sometimes unquestioningly using company-developed presentation material with minimal alteration, or agreeing to edit material to be consistent with the ‘company line’ (a form of ‘ghostwriting’—see below). Remuneration may be considerable, particularly for those involved in company-sponsored ‘satellite’ symposia linked to major conferences, or those on international speaking ‘tours’. In the US, this has led to a formal regulated distinction between meetings supported by ‘untied educational grants’ over which industry has no editorial control, and those for which the ‘educational’ content is are clearly product-related.
These circumstances highlight the need for open disclosure of earnings by the clinician speakers, especially in view of the considerable potential influence of eminent academic figures. A related, and not unreasonable concern, is the time distraction of such speaker bureau activities for academics and senior clinicians from their primary research, teaching, administrative, and clinical responsibilities.
The related broader issue is that of industry involvement in continuing medical education (Moynihan et al. 2008). At present it is believed that 80–90 per cent of CME activities are currently funded and/or organized by industry. Certainly, there has been a concomitant major decline over recent decades in CME auspiced by professional and academic bodies.
Trainees, medical students, nurses, and consumers
Industry contact with these groups has increased in recent years. A number of academics (Rogers et al. 2004; Mohl 2005) and media commentators (Moynihan 2003b) have written on the relationship between industry and trainees or medical students. All emphasize the need for training and awareness of these vulnerable groups on how to relate to industry. There is a curious contradiction in student and trainee attitudes. In general, they are worried about others (such as consultants) accepting gifts, but are themselves unconcerned about the effect of (and may even feel entitled to) gifts such as meals or pens. Some student groups, such as the American Medical Student Association have actively campaigned about these issues (e.g. the student organization ‘PharmFree’). More recently, students at Harvard organized major demonstrations on the influence of industry on academics at that institution (Wilson 2009), and have published a ‘report’ on various medical schools, with those (such as Harvard) who receive large amounts of industry sponsorship being given an ‘F’ (for failure) (Kluger 2009).
An important issue in the training of students and trainees is the ‘hidden medical curriculum’, i.e. the ‘true’ attitudes and behaviour of consultants towards industry that are observed by junior staff, rather than the rhetoric the senior staff espouse. Other vulnerable (and currently more naïve) groups include non-medical clinicians (particularly nurses) and consumer or carer organizations.
This is a fraught and complex area (Moynihan et al. 2008). There was a recent public furor related to the 2008 annual conference of the Royal Australian and New Zealand College of Psychiatrists, whereby the chair of the scientific committee resigned over that College’s refusal to reject industry sponsorship. In the UK, at least one major college conference has declined any industry sponsorship (Moncrieff et al. 2008). However, the issue is not straightforward, as many national and international conferences would require prohibitive registration fees if no industry sponsorship was available. There have been calls for the provision of industry sponsorship of such meetings untied to advertising or exhibition space. While such calls are commendable, it is unrealistic to expect substantial industry commitments without the quid pro quo of such opportunities for marketing. In this light, the announcement in early 2009 by the American Psychiatric Association (Steenhuysen 2009) of a cessation to the practice of allowing industry-sponsored symposia as a major means of earnings for the APA annual scientific conference is striking, and very likely to be seen as a precedent for other major national and international meetings. Furthermore, the APA has decided to phase out industry-sponsored meals at those conferences.
International psychiatric organizations and their relationship to industry
Over the last few decades there have been sotto voce concerns about a lack of probity in the relations between some international clinical organizations and industry, with the worries mainly focusing on the ethics of the bodies themselves, rather than industry. Such concerns appear to have resulted in improved governance of these bodies, tighter financial control, independent auditing procedures, and the reduction in influence of some individuals.
It is important to reiterate that few innovative compounds which have been developed by the public sector have progressed to the point of marketing approval by regulatory authorities. However, it should also be acknowledged that (particularly in recent years) many novel compounds and/or basic mechanisms have been discovered by universities or research institutes, with subsequent licensing of intellectual property rights for drug development to industry.
Related to this, there has been growing concern (Turner et al. 2008; Mathew and Charney 2009) about the high rates of failure (or at the least, excessive delays) in publishing negative trial results. Examples in psychiatry include the prolonged delays in acknowledging some of the negative outcomes of trials in bipolar disorder of topiramate and lamotrigine, and the distortion of the literature on antidepressant efficacy by the failure to publish negative trials. The recent mandatory prior registration of clinical trials should minimize this is as an issue.
Involvement in pharmaceutical industry-sponsored research is not uncommon. Henry et al. (2005b), surveying a large number of Australian specialists, found that participation in such research was more common for those in hospital and/or university (49 per cent) practice than in private practice (33 per cent). The major concerns of the specialists involved in such research were delay in publication or non-publication of key negative findings (5–7 per cent), and concealment of results (2 per cent). About 9 per cent reported at least one event that could represent a breach of research integrity. In a related paper, Henry et al. (2005a) reported that clinicians involved in sponsored research were more likely to have broader involvement with industry. They were significantly more likely to have been offered industry-sponsored items or activities valued at more than AU$500 and support for attending international conferences. Furthermore, they were more likely to be a paid consultant for industry and to be a member of an advisory board.
Acknowledgment of potential financial conflicts of interest in reporting of clinical trials
In 1984, the New England Journal of Medicine became the first of the major medical journals to require authors of original research to disclose any financial ties with companies making products discussed in submitted papers (Angell 2000). Since then, this has become standard practice for most refereed journals. In 2005, Perlis et al. (2005) reported on the first study of the relationship between industry funding and the outcomes of clinical trials in psychiatry. Sixty per cent of trials reported receiving industry sponsorship, and 47 per cent had at least one author with a financial conflict of interest. Of 162 identified randomized controlled trials in major journals, those which reported conflicts of interest were 4.9 times more likely to report positive results.
The issue of appropriate disclosure of conflict of interests remains contentious, as indicated by a recent editorial in JAMA (DeAngelis and Fontanarosa 2009) which commented on controversy over an apparent failure by an author to declare financial relations with industry (by involvement in an industry speakers bureau) in a published report of a NIH-sponsored trial of escitalopram and cognitive therapy.
In one of the few commentaries in this literature by industry-employed psychiatrists, Paul and Tohen of Eli Lilly (2007) spoke on the need for full disclosure of potential conflicts of interest and the requirement for independent verification of research results. They stated: ‘… we too are concerned that the problem of financial [conflict of interest], if not adequately addressed may completely erode the credibility of psychiatric research and thus undermine the essential trust that patients have in their physicians and in the treatments they prescribe’.
Authorship of industry-sponsored trial reports and review articles
There has been recent concern about the apparently common practices of ‘ghostwriting’ and guest authorship. In one of the first reports to raise this issue in psychiatry, Healy and Cattell (2003) examined articles on the antidepressant sertraline published in the late 1990s. They compared publications coordinated by a medical writing agency with articles not coordinated by such agencies. They found that articles linked to these agencies involved more authors and were cited more frequently. Healy and Cattell raised concern about the apparent limited access of the academic authors to the raw data of these trials, and the common failure of these publications to acknowledge the actual, but ‘non-academic’, writers. Similar concerns have been raised about the engagement of physicians, including involvement in the production of ghost-written articles, in promoting off-label indications for gabapentin (Steinman et al. 2006) which included its use in neuropathic pain and bipolar disorder. (It should be noted, however, that some employees of the company involved did courageously publish negative findings; one example of this was the report of Pande et al. (2000)).
In a more recent paper, Ross et al. (2008) used documentation from legal proceedings concerning the anti-inflammatory agent rofecoxib to provide the hitherto best-documented ‘case history’ of the relationship between the pharmaceutical industry, medical publishing companies, and academic clinicians. In a damning exposé, this data- and document-based report detailed pharmaceutical company (in this case, Merck) employees working either independently or in collaboration with medical publishing companies in preparing manuscripts on clinical trials, and subsequently recruiting external academically-affiliated investigators to be the publication ‘authors’. These recruited academic authors were frequently given first or second authorship positions. For scientific review articles, similar processes were documented, with the academic recruits frequently being the sole authors, and moreover being offered honoraria for their participation. While industry financial support was acknowledged in most of the clinical trial reports, this was reported in only half of the review articles. As discussed by the authors, it is unlikely that such practices differ from those of other companies and other products. This report led to robust editorial commentary in JAMA (DeAngelis and Fontanarosa 2008). The continued practice of ghost-written articles has also been raised in the investigations of US Senator Grassley, in this instance involving Wyeth.
A related issue is the reporting of pharmaco-economic analyses, an increasingly important area of research, as such data is now routinely demanded by government agencies responsible for deciding upon subsidization of medications, at either national, regional, or institutional levels. In a report focusing on economic studies of antidepressants, Baker et al. (2003) quantitatively analyzed all articles with original comparative cost or cost-effectiveness outcomes for antidepressants. They found that studies sponsored by manufacturers of newer antidepressants favoured these drugs more than did non-industry studies. Moreover, industry-sponsored modeling studies were more likely to favour industry than were non-industry sponsored studies.
Moynihan and others (Moynihan and Henry 2006) have espoused the concept of ‘disease mongering’—‘the selling of sickness that widens the boundaries of illness in order to grow markets for those who sell and deliver treatments’. According to Moynihan, examples of this disease mongering include the medicalization of the menopause and the portrayal of ‘minor’ problems such as irritable bowel syndrome, high cholesterol, and osteoporosis as serious medical disorders. Healy (2006) has described the major increase in the rates of diagnosis of bipolar disorder as an example of this phenomenon, occurring in response to the growing availability of new mood stabilizers. One concrete outcome of this debate has been the 2004 decision of the European drug regulator to withdraw its approval of premenstrual dysphoric disorder (PMDD) as an indication for the SSRI Prozac, citing that ‘the condition was not a well-established disease entity’ (Moynihan 2004). While many would accept there is some validity to this concept of disease mongering, it is naïve to believe that it is the product of the pharmaceutical industry alone, as there is an equally self-serving academic research industry for many conditions that have been either newly described, or for which there has been a resurgence of interest.
‘Untied’ industry sponsorship of medical school/academic department research
Recent press reports have highlighted the extensive amounts of industry funding of university research programmes, particularly at prestigious institutions such as Harvard. There has been a growing disquiet about the potential influence of such funding, for example on the focus of academic research agendas being on conditions of primary interest to industry drug development programmes. In Australia, there has been vigorous debate about the academic value and propriety of funding by Eli Lilly of a collaborative research programme (Lilly MAP) with the department of psychiatry at the University of Melbourne (Singh et al. 2004; Raven 2004; Malhi 2004).
Why are psychiatrists in the (dubious) ‘lead’?
Despite ripostes from the American Psychiatric Association that there has been an unreasonable focus on psychiatrists in recent US media commentaries, the large number of senior psychiatrists allegedly exposed in these recent reports demands some serious reflection by the profession. In many ways, a strong industry focus on psychiatry would not be unsurprising. Psychotropics are among the most widely prescribed agents, particularly the antidepressants, for which prescribing rates have increased dramatically worldwide since the early 1990s (McManus et al. 2000). The new antipsychotic agents have also been heavily prescribed. Psychotropics have been responsible for a major proportion of profits for a number of companies. Furthermore, the limited distinction between the various new antidepressants and antipsychotics has led to aggressive marketing competition between the responsible companies. Indeed, Moynihan has reported that psychiatrists receive more industry-funded CME than other specialists in Australia (data as yet unpublished). A further factor may be that psychiatrists are among the lowest earning specialty groups, perhaps making them more vulnerable to financial inducements such as travel to overseas conferences or other gifts.
Industry-sponsored events now account for about 90 per cent of all CME activities across medicine. The attraction of educational events with national and international colleagues in expensive hotels locally or overseas is not difficult to appreciate. Furthermore, for academic psychiatrists and other clinical disciplines, research funding through competitive government funding schemes (such as NIH in the US, or MRC in the UK) is increasingly difficult to obtain. Academics also often have few sources of funding other than that offered by industry to attend international scientific meetings.
How are the various bodies responding to this issue?
The ethical guidelines of the American Psychiatric Association (APA 2008), ‘APA Principles of Medical Ethics with Annotations especially Applicable to Psychiatry’)—derived from those of the parent American Medical Association—are virtually silent on the issue of relationships with the pharmaceutical industry. As detailed above, very recently (Steenhuysen 2009) the APA has announced a gradual cessation of industry-sponsored symposia at their annual scientific conference, and a phasing out of industry-sponsored meals.
In contrast to the APA, the UK Royal College of Psychiatrists (RCPsych 2008) has produced a specific publication focusing on this issue: ‘Good Psychiatric Practice: Relationships with Pharmaceutical and other Commercial Organizations’ (Royal College of Psychiatrists Report CR148). This report details guidance on the relationship between individuals, researchers, and the UK College administration itself with industry. It delineates three central principles: transparency, full declaration of relationships, and the need to educate trainees. It does not proscribe relations with industry, rather encouraging transparency and open disclosure. For example, it does not proscribe industry-sponsorship of conference travel or accommodation, nor does it prohibit industry sponsorship of conferences.
In Australia, the Royal Australian and New Zealand College of Psychiatrists has adapted the ethical guidelines of the Royal Australasian College of Physicians (Komesaroff 2005) in the development of the ‘RANZCP Ethical Guideline on The Relationship Between Psychiatrists and the Health Care Industry’ (RANZCP 2008). This ethical guideline provides specific recommendations on clinical trials, sponsorship of conference attendance, support for organization of meetings, receipt of gifts and entertainment, drug samples, remuneration of services, involvement in advisory boards, and involvement of industry with students and CME. As a specific example, these guidelines proscribe receipt of support to attend conferences unless the individual is a speaker or chair. In practice, this recommendation is rarely adhered to, being routinely flouted with respect to both national and international meetings.
In 2006, the American Board of Internal Medicine Foundation (ABIM) and the Institute on Medicine as a Profession (IMAP) published the ABIM-IMAP taskforce policy recommendations on conflicts of interest (Brennan et al. 2006). These recommendations argue that self-regulation has been unsuccessful and that more stringent regulation is necessary. That group proposed the elimination or modification of common practices related to small gifts, pharmaceutical medical samples, continuing medical education, funds for physician travel, speakers bureaux, ghostwriting, and consulting and research contacts. They called for academic medical centres to take the lead in eliminating conflicts of interest between physicians and the healthcare industry.
In 2008, the Association of American Medical Colleges released a formal report on ‘Industry Funding of Medical Education’ (AAMC 2008). This thoughtful, balanced, and robust report began with an acknowledgement of the appropriateness of a partnership with industry, yet the need to manage this:
An effective and principled partnership between academic medical centers and various health industries is critical in order to realize fully the benefits of biomedical research and ensure continued advances in the prevention, diagnosis, and treatment of disease. Appropriate management of this partnership by both academic medical centers and industry is crucial to ensure that it remains principled, thereby sustaining public trust in the proposition that both partners are fundamentally dedicated to the welfare of patients and the improvement of public health.
The AAMC report described the ‘core principles of medical professionalism’ as autonomy, objectivity, and altruism. It commented further upon the relationship with industry: ‘The fault lies not only with industry; the acceptance, indeed the expectation of such financial incentives by academic professionals and their institutions has encouraged these practices’, and ‘In their educational interactions, academic medical institutions and industry are mutually accountable for maintaining a principled partnership based on the primary goal of providing the highest quality of care for patients’.
Specifically the AAMC Report recommends clarity about the extent to which interactions with industry are prohibited, and commends the necessity for educational programmes on the relationship with industry for students, trainees, and teaching faculty. It proscribes receipt of gifts, cautions on the distribution of samples, restricts access of pharmaceutical representatives, and recommends auditing industry-sponsored CME activities (particularly with regard to content and meals). Strikingly, the report strongly discourages involvement of faculty in industry-sponsored speakers bureaux (it should be noted that the industry representatives on the Taskforce declined support of this particular proposal), and proscribes payment for attendance at industry-sponsored meetings and acceptance of gifts at such events. Furthermore, it states that industry-supplied food and meals should be considered as gifts and therefore not accepted. Acceptance of travel funds is proscribed, as is allowing written or oral presentations to be ghost-written. Those involved in decisions about purchases of pharmaceuticals or devices should declare all conflicts of interest. The taskforce also commended convening an expert panel comprised of academic and industry representatives to explore new opportunities and best practice in information exchange between those two groups.
What has been the impact of these ABIM-IMAP and AAMC reports? In a recent commentary, Rothman and Chimonas (2008) describe a surprisingly widespread acceptance of these major shifts in US practice. Contrary to the fears of many, the authors observed no significant movement of academic faculty out of those medical colleges with strong conflict-of-interest policies. Furthermore, they noted ‘an increasing number of accounts of physicians taking personal pride in turning down speakers bureau invitations’. In Australia, a qualitative study of internal medicine physicians has indicated a polarization of responses to ethical guidelines on relations to industry (Osborn 2009).
In an editorial in JAMA, DeAngelis and Fontanarosa (2008), made the following proposals: all clinical trials must be prospectively registered; the contributions of all proposed authors must be detailed and any compensation reported; all funding sources must be acknowledged; financial conflicts of interest must be provided and considered by editors prior to agreement to publish; analysis of data and preparation of the manuscript must have been undertaken by the named authors; statistics must have been conducted by a person not employed by industry; authors not complying with these guidelines must be reported to appropriate authorities; peer reviewers must not divulge details to third parties; industry should have no input into medical education programmes; and physicians should not serve on speakers bureaux or accept gifts from industry. They conclude: ‘Ensuring, maintaining, and strengthening the integrity of medical science must be a priority for everyone’.
Pharmaceutical industry organizations
In late 2008, the Pharmaceutical Research and Manufacturers of America (PhRMA)—the umbrella representative industry group in the US—published an update of its voluntary code of conduct, the ‘Code of Interactions with Healthcare Professionals’ (PhRMA 2008). This differed from previous editions in proscribing gifts such as pens, pads, and mugs, as well as entertainment and recreational benefits such as tickets to the theatre or sporting events. It did, however, allow for provision of starter packs and engagement of clinicians in speakers bureaux.
In Australia, the analogous body—Medicines Australia—published the 15th Edition of its ‘Code of Conduct’ in March 2007 (Medicines Australia 2007). For the first time, and under the direction of the Australian Competition Tribunal, this code detailed mandated web disclosure of all industry-sponsored educational and marketing activities in Australia and the associated costs, though at this stage not disclosure of the names of clinicians receiving remuneration. This would appear to be the first national mandated detailing of such activities, and has revealed that approximately 30,000 such events occur each year, involving at least 800,000 attendances, costing about AU$32 million p.a. In a recent article in the Weekend Australian (Cresswell 2009), there was reported concern over the number of ‘educational events for doctors that include weekends costing more than AU$300,000 at five-star hotels’.
Recommendations and remaining areas of uncertainty
Where do these developments leave psychiatry and the broader medical community? There is clearly a need for the medical profession to get its own house in order. Self-regulation has not worked, despite the best of intents. This is a problem for both industry and the profession. Psychiatrists now have a major credibility problem with the public; it is an issue of trust.
The central principles of the relationship must be integrity and transparency. Inadequacies in disclosure have been at the centre of recent scandals in the US. Should there be full disclosure, as proposed by Grassley? The ground is already moving rapidly under our feet. A number of US companies have recently decided to publicly detail all remuneration to clinicians. In Australia, all promotional and educational events are disclosed by court order, though clinician payments are not, as yet, required to be reported.
We have no alternative but to drastically improve the transparency of the relationship, both in terms of remuneration received and disclosure of any potential conflicts of interest (in all publications, media statements, and guidelines). However, if we go down the route of disclosure of earnings from industry, questions remain. First, should this be in broad terms (such as a generic declaration of remuneration from activities such as advisory boards, consultancies, honoraria for speaking engagements, sponsored travel and/or accommodation to meetings, involvement in industry-sponsored trials, payment for publications written with industry, retainers, or shares in pharmaceutical companies) or should actual dollar earnings be disclosed? I believe that we will inevitably need to declare actual earnings, and should do so soon, but I accept that this may be too great a demand for the medical profession at this point in time. Second, to whom should such details be provided? To the public via websites, such as that of Medicines Australia? For clinicians, to the relevant professional bodies? For academics, to university administrators?
While the details of such disclosure will need to be determined, it is clear that we must expeditiously formalize a relationship of integrity and transparency between the medical profession and the pharmaceutical industry. Furthermore, universities and other medical bodies, such as the professional colleges, should seriously consider developing detailed recommendations such as those of the AAMC (Greenland 2009).
The credibility and destiny of medicine are in our hands. We must not fumble the ball at this critical juncture.
Potential conflicts of interest
In the financial year 2007–2008, Philip Mitchell was paid a total of AU$6,500 for lecture honoraria, consultancies, and advisory board membership from pharmaceutical companies that manufacture and market psychotropic agents (AstraZeneca, Eli Lilly, and Pfizer). He also received travel support to attend an international scientific forum at which he gave an invited lecture in a symposium in the main programme of the meeting. He has not been a member of a pharmaceutical company advisory board since early 2008. Since the beginning of 2009, he has donated all remuneration from industry to charitable organizations. He has never owned stocks in pharmaceutical companies, nor received retainers. He has been a site investigator for a number of industry-sponsored trials, the most recent being in 2004. Mitchell has also received remuneration from state and federal health departments for various committee memberships, including three years serving on the Australian Drug Evaluation Committee (the advisory committee to the Australian drug regulator, the Therapeutic Goods Administration).
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