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Financial ties between dsm-iv panel members and the pharmaceutical industryRegular Article
Financial Ties between DSM-IV Panel
Members and the Pharmaceutical
Lisa Cosgrove a Sheldon Krimsky b Manisha Vijayaraghavan a a University of Massachusetts, Boston, Mass. , and b Tufts University, Medford, Mass. , USA Key Words
cies (22%) and speakers bureau (16%). Conclusions: Our
Confl icts of interest ؒ Ethics ؒ Financial interests ؒ inquiry into the relationships between DSM panel mem- bers and the pharmaceutical industry demonstrates that there are strong fi nancial ties between the industry and those who are responsible for developing and modifying Abstract
the diagnostic criteria for mental illness. The connec- Background: Increasing attention has been given to the
tions are especially strong in those diagnostic areas transparency of potential confl icts of interest in clinical where drugs are the fi rst line of treatment for mental dis- medicine and biomedical sciences, particularly in journal orders. Full disclosure by DSM panel members of their publishing and science advisory panels. The authors ex- fi nancial relationships with for-profi t entities that manu- amined the degree and type of fi nancial ties to the phar- facture drugs used in the treatment of mental illness is maceutical industry of panel members responsible for revisions of the Diagnostic and Statistical Manual of Mental Disorders (DSM) . Methods: By using multimodal
screening techniques the authors investigated the fi nan-
cial ties to the pharmaceutical industry of 170 panel
Medical journals began introducing conﬂ ict-of-inter- members who contributed to the diagnostic criteria pro- est (COI) disclosure requirements for authors two de- duced for the DSM-IV and the DSM-IV-TR. Results: Of the
cades ago beginning with articles of original research. A 170 DSM panel members 95 (56%) had one or more fi - growing awareness of the importance of author disclosure nancial associations with companies in the pharmaceuti- in biomedical publications is reﬂ ected in the rising num- cal industry. One hundred percent of the members of the ber of medical journals that have adopted COI policies panels on ‘Mood Disorders’ and ‘Schizophrenia and Oth- over the past decade and the support for such policies er Psychotic Disorders’ had fi nancial ties to drug compa- among professional societies. If ﬁ nancial COI among nies. The leading categories of fi nancial interest held by medical researchers can bias the outcome of a study (as panel members were research funding (42%), consultan- recent research shows) [1, 2] , there is as much reason to Department of Urban and Environmental Policy and Planning Tel. +1 617 627 3394, Fax +1 617 627 3377, E-Mail [email protected] believe it can also bias the recommendations made by States, most of whom have taken instruction on the DSM members of advisory panels [3–5] . The importance of  . protecting the integrity and public trust in scientiﬁ c and In this study we investigated the ﬁ nancial relationships medical advisory committees has been widely discussed that members of the advisory boards to the DSM-IV and [6, 7] . Yet, there remain areas that lack the transparency the DSM-IV-TR have had with the pharmaceutical in- of ﬁ nancial COIs that have become standard procedures dustry, which manufactures drugs used by clinicians for the treatment of mental disorders. We assessed the extent To date there has been no study examining the rela- and types of ﬁ nancial relationships for each of the diag- tionship between the pharmaceutical industry and the nostic panels. scientists comprising the advisory panels that recom-mended changes in the Diagnostic and Statistical Manu-al of Mental Disorders ( DSM ) , a leading medical manual used for the diagnosis of psychiatric disorders. Pharma- The Diagnostic and Statistical Manual for Mental Disorders ceutical companies provide substantial funding for con- ( DSM ) is organized around working groups or panels. Most of the ventions, journals, and research related to what is includ- panels address a speciﬁ c category such as ‘Mood Disorders’. The ed in the DSM, because what is considered diagnosable members of each panel have signiﬁ cant inﬂ uence in determining directly impacts the sale of their drugs  . This ‘uneasy whether a new diagnosis should be added or an older diagnosis re-vised for the next edition of the manual. From the latest edition of alliance’  was evidenced when a prominent journal the DSM (DSM-IV) and the edition with text revision (DSM-IV- reported that it was difﬁ cult to ﬁ nd research psychiatrists TR), we identiﬁ ed 228 individuals associated with the development to write an editorial about the treatment of depression of the volume. After deleting clerical staff, we were left with 170 who did not have ﬁ nancial ties to the pharmaceutical expert members who comprised a total of 18 distinct panels. companies that manufacture antidepressant medications Each panel member was put through a series of ‘screens’ to de- termine whether he or she has had any ﬁ nancial associations with  . Recently some members of the American Psychiat- one or more pharmaceutical companies whose business is poten- ric Association (APA) have expressed concern about the tially affected by decisions or recommendations made by the pan- potential for COI that arises with the increase in industry el. The ‘screens’ involved tracking publications of the panel mem- support  . For example, at the annual meeting of the ber for disclosures of potential COIs (in journals that have disclo- APA in 2004 there were 54 industry-supported symposia. sure policies), and submitting the panel member’s name into the news media database Lexis-Nexis and Internet search engines. We Also, pharmaceutical advertising revenue in APA jour- also submitted panel members’ names into databases of the US nals, totaling USD 7.5 million in 2003, increased 22% in Patent and Trademark Ofﬁ ce to screen for holdings of intellectual property in a drug whose sales could be affected by recommenda-tions of the DSM. For example, the FDA’s approval of Sarafem (ﬂ uoxetine hydrochloride) for the treatment of premenstrual dys-phoric disorder was contingent upon expert testimony that con- Objectives of the Study
cluded that premenstrual dysphoric disorder was a distinct clinical entity that should be included as a mental disorder in the DSM Continuously produced since 1952 by the APA, the  . DSM, currently in its sixth revision  , is the ofﬁ cial Panel members were screened for any ﬁ nancial afﬁ liations they manual for psychiatric diagnosis in the United States.1 had with the drug industry between the years 1989 (the DSM-IV was published in 1994) through 2004. By using multiple screening Its classiﬁ cation system is used by government agencies techniques to gather published or Internet data on ﬁ nancial afﬁ lia- and for all mental health professionals who seek third tions, we were able to avoid a methodology that relied solely on party reimbursements. The manual provides the stan- self-reporting (e.g., surveying panel members). dard psychiatric taxonomy found in psychiatry and psy- Financial associations of interest for this study include: hono- chology textbooks  . Nearly 400,000 mental health raria, equity holdings in a drug company; principal in a startup company, member of a scientiﬁ c advisory board or speakers bureau professionals, including psychiatric nurses, social work- of a drug company; expert witness for a company in litigation; pat- ers, psychologists and psychiatrists practice in the United ent or copyright holder; consultancy; gifts from drug companies including travel, grants, contracts, and research materials. We use the term ‘ﬁ nancial interest’ in describing the relationship between panel members and the pharmaceutical industry rather than the 1 Outside of the United States the ofﬁ cial coding system for mental illness term ‘conﬂ ict of interest’ (COI) because the latter term implies an is the International Statistical Classiﬁ cation of Diseases and Related Health interpretation of the interest. Thus, we choose not to deﬁ ne COI. Problems, 10th Revision (ICD-10). According to the DSM IV-TR, the prepara-tion of DSM-IV has been closely coordinated with the preparation of Chapter Rather, we identify categories of ﬁ nancial interest and reserve judg- V ‘Mental and Behavioural Disorders’ of ICD-10.
ment on whether they represent a real, perceived, or potential COI. Our approach is congruent with other publications that make a distinction between the ﬁ nding of ‘ﬁ nancial interests’ and the judg- We chose 20% of the panel members (every ﬁ fth name) for an ment of ‘conﬂ icts of interest’ [19–21] . Speciﬁ cally, there is less dis- interrater reliability test. One investigator, who was not involved agreement about what constitutes a ‘ﬁ nancial interest’ than there in coding, reviewed the data for 19 names representing 44 coding is about what makes a ‘conﬂ ict of interest’. decisions. This investigator missed 2 coding decisions; all other The speciﬁ c screening methods we applied included Lexis-Nex- coding decisions matched the results of the coding team. Our test is, Internet search engines (such as Google and Yahoo), the US Pat- demonstrated that the most likely error of using another coder was ent and Trademark Ofﬁ ce Internet Site on patents pending or missing a ﬁ nancial interest. This error was minimized by having awarded, and Medline. Each ﬁ nding of a panel member’s ﬁ nancial three independent coders who compared ﬁ ndings and reached con- connection to a drug company was coded: H = honorarium; RF = sensus. Our methodology tends to err in understating rather than research funding; RM = research materials (equipment, drugs, cell overstating the ﬁ nancial interests of panel members. cultures, etc); EQ = equity in a company; CB = member of a cor-porate board (advisory board or board of directors); SB = speakers bureau; CON = consultant; ET = expert testimony; DINP = drug industry nonproﬁ t (a nonproﬁ t organization funded primarily by the pharmaceutical industry such as the Novartis Foundation);P = holds a patent, patent application or royalties on a product rel-evant to the treatment of mental disorders, and CIFS = collaborator Of the 170 DSM panel members 95 (56%) had one or in industry-funded study. Individuals classiﬁ ed under CIFS are more of the eleven ﬁ nancial links to a company in the DSM panel members who participated in a study as a coinvestiga- pharmaceutical industry. Figure 1 shows the percentages tor or collaborator, where the principal investigator (rather than the of the panel members listed in the DSM-IV and DSM- panel member) was described as funded by the pharmaceutical company. IV-TR with ﬁ nancial linkages to drug companies. Unless A DSM panel member who received a fee from a drug company otherwise noted, the percentages given for each DSM cat- for speaking at a session of a symposium sponsored by a pharma- egory include the members from both the 1994 and 2000 ceutical company was coded as an H (received an honorarium). editions. In 6 out of 18 panels more than 80% of panel However, when a university or medical school receives unrestrict- members were found to have ﬁ nancial ties to the phar- ed educational grants from a drug company, the company usually does not have a role in selecting the speakers, setting the honoraria, maceutical industry. These include 100% of the panels or signing the speaker’s honoraria check. For our study, a panel for the ‘Mood Disorders Work Group’ (n = 8) and the member who spoke at a symposium but did not receive direct pay- ‘Schizophrenia and Other Psychotic Disorders Work ment from a drug company (e.g., he/she spoke at a professional Group’ (n = 7), 81% for ‘Anxiety Disorders’ (n = 16), 83% meeting or Grand Rounds of a medical school sponsored wholly or for ‘Eating Disorders’ (n = 6), 88% for ‘Medication-In- in part by a pharmaceutical company) was not coded as H. In oth-er words, lecture honoraria paid by a university were considered as duced Movement Disorders’ (n = 8) and 83% for ‘Pre- nondisclosable ﬁ nancial interests for the purpose of this study. Al- menstrual Dysphoric Disorders’ (n = 6) (see ﬁ g. 1 ). The though not included in our analysis, we found 23 panel members mental illness categories denoted by ‘Mood Disorders’ who gave talks sponsored, in part, by drug companies but who were and ‘Schizophrenia and Other Psychotic Disorders’ are compensated by universities under unrestricted grants. the two main categories for which psychopharmacologi- While our methodology allowed us to ascertain varied ﬁ nancial relationships that existed between DSM panel members and the cal treatment is standard practice, whereas it is far less pharmaceutical industry during the period of analysis, it did not likely for individuals diagnosed with ‘Substance-Related allow us to make causal inferences about those relationships. We Disorders’ (17%; n = 6) to receive such treatment (unless could not determine whether, or to what extent, an individual’s as- there is a coexisting mental disorder such as a mood dis- sociation with the pharmaceutical industry inﬂ uenced his/her be- havior on a DSM panel or, conversely, whether participation on a DSM panel inﬂ uenced his/her subsequent involvement with the The most frequent ﬁ nancial link we found between the pharmaceutical industry. For the most part, the data on panel mem- DSM expert panels and the drug industry is ‘research ber associations with the pharmaceutical industry are atemporal. funding’. Among the 170 panel members, 42% received Some of the ﬁ nancial relationships might have occurred before, research funding from pharmaceutical companies; 22% during, or after publication of the DSM volumes. Ethical consider- were consultants and 16% served as members of a drug ations are relevant whether the panel member’s involvement in the drug industry occurred prior to or after DSM publication. company’s speakers bureau (see ﬁ g. 2 ). Three investigators independently conducted screens on the Of those panel members who had ﬁ nancial links with panel members. Any questions about coding were resolved by a the pharmaceutical industry (n = 95) 76% had research fourth investigator. No panel member was coded as having a ﬁ nan- funding, 40% had consulting income, 29% served on a cial connection unless there was unambiguous information con- speakers bureau, and 25% received honoraria other than from serving on a speakers bureau (see ﬁ g. 3 ). More than half of the panel members with ﬁ nancial ties were found Fig. 1. Percentage of panel members of the DSM with ﬁ nancial ties.
Delirium, Dementia, Amnestic and Other Cognitive Schizophrenia and Other Psychotic Disorders Disorders Usually First Diagnosed during Infancy, Sexual and Gender Identity Disorders (TR) Medication-Induced Movement Disorders (TR) Committee on Psychiatric Diagnosis and Assessment Joint Committee of the Board of Trustees and Assembly of District Branches on Issues to DSM-IV to have more than one category of ﬁ nancial interests with Limitations
the pharmaceutical industry. Eleven panel members had ﬁ ve different ﬁ nancial ties (see ﬁ g. 4 ). When there were The results of this study need to be interpreted in light competing coding categories, only the most precise de- of several limitations. First, it is reasonable to expect that scriptor was coded. For example, a panel member listed some types of ﬁ nancial relationships were not detected by on a speakers bureau, where he/she received honoraria, our screening methods. For example, expert witnesses was coded only as ‘SB’. Hence, the percentages in ﬁ gure 4 serving in litigation are difﬁ cult to detect with standard represent the most conservative estimate of DSM panel screening tools. Second, our screening methods fell short members with multiple ﬁ nancial associations to the phar- of allowing us to quantify or to set a temporal sequence for the association. In most instances information about the amount of money received from pharmaceutical com- Fig. 2. Categories of ﬁ nancial interest held
by DSM Panel Members: total members (n = 170). RF = Research funding; CON = member of a corporate board; H = hono-rarium; CIFS = collaborator in industry- funded study; DINP = drug industry non-proﬁ t afﬁ liation; RM = research materials; Fig. 3. Categories of ﬁ nancial interest held
nancial interests (n = 95). RF = Research funding; CON = consultant; SB = speakers bureau; CB = member of a corporate board; H = honorarium; CIFS = collaborator in in- dustry-funded study; DINP = drug industry nonproﬁ t afﬁ liation; RM = research materi- als; EQ = equity in a company; P = patent; ET = expert testimony. Panel members with multiple financial interest Fig. 4. DSM panel members with multiple
ﬁ nancial interests.
panies was not disclosed. Also, disclosures were reported ceutical industry, because of the greater likelihood that strictly in terms of whether a person was a current or past the drug industry may be exerting an undue inﬂ uence on recipient of industry support. Even among journals that the DSM. As previously noted, the DSM working groups have set high standards on author disclosure, no speciﬁ c that had the highest percentage of ﬁ nancial ties to the dates are given. For example, the following is a typical pharmaceutical industry were those groups working in disclosure statement: ‘Dr. X has received honoraria and diagnostic areas (e.g., mood disorders and psychotic dis- research support from Company Y and Company Z and orders) where pharmacological interventions are stan- he also serves on their speakers bureau.’ Because it was dard treatment. In light of the extreme proﬁ tability of the not possible to quantify these relationships or locate the psychotropic drug market, the connections found in this precise time they occurred, only qualitative conclusions study between the DSM and the pharmaceutical industry can be drawn about the extent of the ﬁ nancial relation- are cause for concern. For example, antidepressants and ships of DSM panel members with the pharmaceutical antipsychotics were the fourth and ﬁ fth leading therapy industry. Also, no conclusions can be drawn about the classes of drugs in 2004, with annual global sales totaling impact these relationships may have had on a panel mem- USD 20.3 and USD 14.1 billion dollars, respectively  . ber’s behavior. However, there are ethical concerns in One antidepressant alone, venlafaxine (Effexor, Wyeth) these relationships regardless of the amount of money giv- achieved USD 3.7 billion in sales in 2004  . The anti- en or the timing of the ﬁ nancial association. A ﬁ nancial psychotic drug market has been identiﬁ ed as one of main relationship held during (or just before) participation as therapeutic areas for global market growth with sales of an expert panel member might inﬂ uence or be perceived USD 8.5 billion in 2002 and projected sales of USD 18.2 to inﬂ uence the outcome of a DSM work group. On the billion by 2007  . Therefore, we recommend that the other hand, if their association with the pharmaceutical APA institute a disclosure policy for panel members of industry occurred after work on the panel was completed, the DSM who have ﬁ nancial ties to the drug industry. panel members might be perceived as using their prestige This is consistent with the trend for greater transparency to leverage lucrative consulting arrangements with the in the membership of federal advisory panels. Raising pharmaceutical industry. In the latter case public trust in awareness about the real or perceived COI of panel mem- the independence of medical science is eroded when for- bers is an important public health issue [27–32] . mer panel members, who are valued as ‘thought leaders’ Transparency should also apply to journal publication  , exert their inﬂ uence on prescription practices through [33, 34] . We undertook a search of Ulrich’s Periodicals consulting, public speaking, and participation in industry- Directory using the terms ‘psychiatry and drugs’, ‘psycho- pharmacology’, ‘drugs and mental illness’ and ‘psychiatry Finally, we relied on self-reported disclosure data that and medication’. When restricted to the descriptors ‘ac- was available in the open literature. Author noncompli- tive’, ‘academic/scholarly’, ‘English language’ and ‘refer- ance with journal COI policies has been cited as a prob- eed journals’, the search identiﬁ ed 45 journals of psychi- lem  . Therefore, the percentages of DSM panel mem- atry. Of those, 19 had COI disclosure policies (42%). bers identiﬁ ed as having ﬁ nancial ties and the variety of Many of the ﬁ nancial ties that were found in this study their ties to the pharmaceutical industry should be con- were discovered because of these disclosure policies. Thus, we also recommend that all psychiatry journals adopt COI policies following the recommendations of the International Committee of Medical Journal Editors. Comments
Receiving ﬁ nancial support from a pharmaceutical Acknowledgments
company should not automatically disqualify an individ-ual from serving on a DSM panel. However, the public We are most grateful for the assistance of two UMass graduate students, Michelle Levinson and Greg Noga and one Tufts Univer- and mental health professionals have a right to know sity undergraduate student Naomi Mower, all of whom conducted about these ﬁ nancial ties, because pharmaceutical com- preliminary searches. Ms. Mower participated through a summer panies have a vested interest in what mental disorders are scholars grant from Tufts University provided through the univer- included in the DSM. Transparency is especially impor- sity’s endowment. Dr. Krimsky was her mentor under the program. tant when there are multiple and continuous ﬁ nancial He received a small stipend for supplies. No other participants of the study were supported by grants. relationships between panel members and the pharma- References
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