Rapid Responses to:

EDITOR'S CHOICE: Fiona Godlee Doctors, patients, and the drug industry BMJ 2009; 338: b463 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

So free we seem, so fettered fast we are!

BM Hegde   (6 February 2009)

Doctors, Drug Companies and Medical Journals

Christopher M Thorpe Thorpe   (6 February 2009)

Drug industry and some scientific society:the blameable partnership.

Vincenzo Fricchione Parise   (6 February 2009)

They are not alone

Michael B. Mundorff   (8 February 2009)

Big Pharma and Little Doctors

Hugh Mann   (8 February 2009)

Another multi-stakeolder forum but some important conclusions on independent information for patients

Teresa Leonardo Alves, Dr. Tim Reed, Director, Health Action International   (11 February 2009)

Drug Companies & Doctors: A Story of Corruption

Anthony G Cummins   (12 February 2009)

What can we do to protect our professionalism?

Rahul Bhattacharya   (13 February 2009)

Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins

Jonathan Leo, Jeffrey Lacasse, Assistant Professor of Social Work, Arizona State University   (5 March 2009)

Potential conflicts of interest: more information from JAMA

Sharon Davies   (11 March 2009)

Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins

Steven N Wagner   (20 March 2009)

NIH promotes the rise of merchant investigators.

Richard G Fiddian-Green   (22 March 2009)

David and Goliath?

Peter M English   (25 March 2009)

Re: Potential conflicts of interest: more information from JAMA

Peter J Flegg   (25 March 2009)

Stealth Advertising and Academic Stalking

David O Antonuccio, Ph.D., David Healy, M.D., Professor, North Wales Dept of Psychological Medicine, Cardiff University, Wales LL57 2PW   (30 March 2009)

Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins

Robert G. Robinson   (15 April 2009)

Conflicts Regarding Conflicts About Conflicts of Interest

Jeffrey R. Lacasse, Jonathan Leo   (17 April 2009)

Re: Conflicts Regarding Conflicts About Conflicts of Interest

Laura S. Boylan   (24 April 2009)

So free we seem, so fettered fast we are! 6 February 2009
BM Hegde, Editor in Chief, Journal of the Science of Healing Outcomes, Mangalore-575 004, India. Send response to journal: Re: So free we seem, so fettered fast we are!	Dear Fiona Godlee, Another pet project of mine. Our present professional life (so called academic life) seems to be so closely linked to drug company largesse that it is almost impossible to tone it down in any way. The earlier we get rid of the menace of the unholy nexus between greedy colleagues that bend over backwards to please their masters in the industry and the cunning ways the latter use to get what they want from the former the better for our hapless patients. I do not think that there is any other option left. Newer diseases would be invented to suit new drug use-restless leg syndrome is a good example! I just returned from a large academic meeting where I was the only speaker that did not get any assistance from the pharmaceutical lobby. Most talks were sponsored by the latter. One of the speakers from a drug major from the US was supposed to be a leader in statin research. The following morning National Dailies were screaming with the headlines: “The Newton of lipid research is in the city” to deliver a special lecture on cholesterol and its dangers! All the other important national events took the back seat. One could assess the industry’s clout even in the media. I am sure the statin sales must have doubled. The lavish hospitality at the venue, the five-star comforts for delegates housed in the venue itself and their business class air travels would be the envy of even the beleaguered captains of the global melt down companies in the west. Compare this with the 15th Century statue of the RCP London that “no Fellow shall send a bill to his patients.” I am happy that the RCP London has taken the lead in clearing the mess in this area. Good luck, President Ian Gilmore! Yours ever, bmhegde Competing interests: None declared
Doctors, Drug Companies and Medical Journals 6 February 2009
Christopher M Thorpe Thorpe, Consultant in Anaesthetics and Intensive Care Medicine Ysbyty Gwynedd, Bangor LL59 5TH Send response to journal: Re: Doctors, Drug Companies and Medical Journals	On opening the BMJ this week the front cover highlighted the relationship between the drug industry and the medical profession. The next thing that fell out was the review on reflux disease sponsored by Reckitt Benckiser, with an advert for Gaviscon on the back. So I opened the main journal, eager to find out what the editor felt about drug company sponsorship. On the first page, I found that Depo-Provera is a simple injectable contraceptive. Turning the page I discovered that Omacor can help patients survive an MI. The next page informed me that Codipar plugs the pain gap, and the following page that Amias can help patients with chronic heart failure. Opposite this last advert I found the editors choice, highlighting the theme for the week. In total I counted 20 adverts in the journal. Control of the relationship between drug companies and doctors is important, however I suspect that the funding provided by drug companies is an essential part of continuing medical education as it stands, and by this I mean unrestricted educational grants for meetings and also money paid to medical journals. Competing interests: I have organised meetings using unrestricted educational grants from drug companies
Drug industry and some scientific society:the blameable partnership. 6 February 2009
Vincenzo Fricchione Parise, psychiatrist Avellino - 83100 (Italy) Send response to journal: Re: Drug industry and some scientific society:the blameable partnership.	In the last few years the psychiatric field whas been characterized by a lot of me-too, very expensive drugs, which at best are not inferior to previous drugs. To give an example: escitalopram (from citalopram), paliperidon (from risperidon), mirtazapine (from mianserine), pregabalin (from gabapentin), etc. Many new antipsychotics aren't better than older ones for effectiveness or side effects. In Italy, sad to say, in medical journals published by some scientific societies it's possible to read articles that are plain pseudo-scientific and advertising. No warning of conflict of interest or other signalling are traceable in them. Last but not least evidence is, in my opinion, in "Quaderni Italiani di Psichiatria" (published by SIP, Italian Psychiatric Association) and "Facts, News & Views" (published by SINPF, Italian Neuropsychopharmacologic Society). Who should be the guardian angels of ethics? I'm envious of your Royal College of Physicians...and my compliments to Iain Chalmers of NHS and to BMJ group. Competing interests: None declared
They are not alone 8 February 2009
Michael B. Mundorff, Research/Education Primary Children's Medical Center, Salt Lake City, Utah USA 84113 Send response to journal: Re: They are not alone	While I do not disagree with the views expressed regarding pharmaceutical companies and their interaction with physicians and CME, they are not the only sinners. The same could just as easily be said about medical device manufacturers and their relationships with clinicians, such as for joint prosthetic manufacturers and orthopedic surgeons or pacemakers and cardiologists. If we are going to address this issue, let's do it comprehensively, not just for pharma. I have this sinking feeling that after the victory handed to medical device manufacturers on a silver platter by the US Supreme Court decision in Riegel v. Medtronic, they are in need of even more oversight and circumspection. Competing interests: None declared
Big Pharma and Little Doctors 8 February 2009
Hugh Mann, Physician Eagle Rock, MO 65641 USA Send response to journal: Re: Big Pharma and Little Doctors	The relationship between the drug industry and doctors is upside down and backwards. Although the drug industry is motivated primarily by profit, lacks clinical experience and judgment, and has a history of egregious dishonesty, the drug industry nonetheless dominates doctors. The drug industry’s economic might, political connections, deceptive marketing, biased research, and self-serving educational functions render even experienced doctors little more than medical students who seek a passing grade and prize the prescription pad as a badge of honor and raison d'être. It’s no wonder that doctors and medical journals are now half-heartedly and belatedly trying to emancipate themselves from the drug industry’s hegemony and patronage, while the drug industry is hypocritically trying to maintain the status quo. And it’s no wonder that healthcare is so frustrating, expensive, confusing, ineffective, and dangerous. How sad for doctors, patients, and patients’ families, who suffer along with patients and struggle to pay inflated medical bills. Those who seek to defend the drug industry’s right to monopolize healthcare, gouge the public, and make rapacious, extravagant profits should read Mark 8:36, “For what shall it profit a man, if he shall gain the whole world, and lose his own soul?” Competing interests: None declared
Another multi-stakeolder forum but some important conclusions on independent information for patients 11 February 2009
Teresa Leonardo Alves, Coordinator, Health Action International (Europe) 1054 HK Amsterdam, Dr. Tim Reed, Director, Health Action International Send response to journal: Re: Another multi-stakeolder forum but some important conclusions on independent information for patients	Any attempt to improve patient care is to be welcomed, and in this context Health Action International (HAI) welcomes the Royal College of Physician’s (RCP) Innovating for Health Report. However, we believe that the multi-stakeholder approach is an unpredictable instrument that, at worst, can be used to hijack the often laudable aims and ambitions of an investigation. The primary flaw lies in denying, or at least marginalising the fact that all stakeholders have interests, which while sometimes coincidental, are often under tension. This denial is reflected in both the execution and tone of the RCP report, leading readers to believe that the stakeholders engaged were, in fact, all moving towards the same goal and driven by the same aspirations. This is patently not the case and the pharmaceutical industry cannot be regarded as an equal partner with the other stakeholders in this forum. The pharmaceutical industry is not a healthcare provider, and their participation in such fora will only bring about increased patient care if it coincides with their prime objective of financial accountability to shareholders. As a result, and in spite of the most damning warning yet of industrial interests infiltrating the UK healthcare system in the House of Commons Select Committee report on the influence of the pharmaceutical industry (2005), it is no surprise that the RCP shows support for the idea of increased partnership. By disregarding the asymmetry of stakeholder interests from the outset, the RCP overlooked the need for conflict of interest declarations and none are included in the final report. Those who gave evidence should have prima facie declared any financial links with the pharmaceutical industry. A simple internet search reveals that evidence was given to the committee by apparently non-industry stakeholders that were, in fact, sponsored by the pharmaceutical industry. Such evidence should not be treated as equal to that of interest free testimony. The absence of a conflict of interest declaration damages the validity of the report as a whole. Nonetheless, the RCP working party does seem to have steered a cautious path through the evidence they gathered and some of the recommendations contain valuable insight. For example, the recommendations identify a need for independent, unbiased, relevant and tailored information to patients about medicines. We strongly support this conclusion and we are appalled that the European Commission’s (EC) proposed directive on ‘information to patients’ contradicts this principle of independent, unbiased, and relevant information. In a world where unchecked self-regulating markets have been thoroughly discredited, it is irresponsible for the EC to encourage the provision of information by the pharmaceutical industry, which would undoubtedly open the flood-gates for pharma-endorsed disease awareness campaigns and direct to consumer advertising of prescription medicines. In contrast, the RCP recommendations recognise the reality that less promotional information from the industry and more unbiased information from independent sources would go a long way towards promoting public health. But, did we really need another ‘multi-stakeholder’ initiative to tell us this? Wouldn’t it have been more insightful to produce a report that acknowledged the inherent conflicts between the interests of healthcare providers, patients (whether funded by the pharmaceutical industry or not), regulators, governments and the pharmaceutical industry? It is time to concede the difficulties with the multi-stakeholder model, seize the initiative, and with strong leadership, reassign the pharmaceutical industry the more appropriate role as servants to public health, rather than meekly inviting them to the table as partners. Competing interests: None declared
Drug Companies & Doctors: A Story of Corruption 12 February 2009
Anthony G Cummins, Lecturer Department of General Practice, RCSI Medical School, Dublin 2, Ireland Send response to journal: Re: Drug Companies & Doctors: A Story of Corruption	This issue was also highlighted in the January 15th issue of the New York Review of Books. The title above was used in this article by its author, Marcia Angell, former editor of The New England Journal of Medicine. The article was a detailed review of three recently published books on the major pharmaceutical scandals in the USA over the last few years. Echoing Iain Chalmers' comments it is clear from each of the three stories covered that not alone did senior players in the pharmaceutical industry behave well below acceptable standards but they were aided throughout by a greedy medical profession. Many lessons have to be learned both in the USA and in Europe. Royal colleges, medical schools, grant-funding bodies etc all have a role to play in ensuring thorough rigorous monitoring of standards. A notable issue identified in these USA investigations was the non- publication of negative results deemed inimical to commercial concerns of the pharmaceutical companies. All trials MUST be published so that meaningful conclusions can be made about best treatment choices. In deciding on treatment choices in future all information should be available to the clinician and the patient. Evidence-based medicine yes but, currently, the evidence base in some areas (and maybe more) must be suspect. Competing interests: None declared
What can we do to protect our professionalism? 13 February 2009
Rahul Bhattacharya, Specialist Registrar in Psychiatry, Charing Cross and St Mary's Training Scheme St Charles Hospital, Exmoor Street, London W10 6DZ Send response to journal: Re: What can we do to protect our professionalism?	The plethora of articles and views on the topic of relationship between the doctor and the pharmaceutical industry highlights the very topical anxiety that surrounds this relationship. The relationship is under scrutiny as it threatens our professionalism. It is refreshing to see the 'multi-stakeholder' consultation model, as too often we seem to ignore the complexity of the dynamics that surrounds prescribing. It is not a simple bipolar construct. There are the national and local organizational resource management perspectives, there is the best interest of the patient often accompanied by views of their carers, and there is the pharmaceutical industry financial interest and the perspective of the doctor. The lack of awareness of the complexity of the issue can potentially leave us vulnerable to influence, and threaten our professionalism. I would therefore argue in favour of inclusion of this awareness as a part of the 'core curriculum' for all medical professionals. The General Medical Council publication 'Tomorrow's Doctors' (2003, http://www.gmc- uk.org/education/undergraduate/GMC_tomorrows_doctors.pdf) does not explicitly mention awareness of the 'conflict of interest', or the issues surrounding contact with the pharmaceutical industry as a part of the core curriculum. The document makes it implicit that the trainee should obtain the skills to interpret research, however I believe this should be supplemented by the awareness of the ethical issues the surround the relationship between the doctors and the industry. The pharmaceutical industry essentially 'self-regulates' the contact with doctors through its ABPI Code of Practice. However, if we really believe it 'takes two to tango', then we should be proactive on our part, by promoting awareness and training of these issues within the medical profession. This possibly along with the medical profession’s own code of practice can potentially minimise the threat that this tainted relationship poses to our profession. Competing interests: None declared
Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins 5 March 2009
Jonathan Leo, Associate Professor of Neuroanatomy Lincoln Memorial University , Harrogate TN 37752, Jeffrey Lacasse, Assistant Professor of Social Work, Arizona State University Send response to journal: Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins	Central to the idea of evidence-based medicine is that the choices made by patients and doctors to use a certain treatment should at least in part be based on scientific studies published in peer reviewed academic journals. For a patient diagnosed with a mental disorder, the choice often comes down to whether to use behavioral therapy, psychotropic medications, or a combination of the two. We think the following story will shed some light on how conflicts of interest can complicate the decision making process. Earlier this year, The Journal of the American Medical Association (JAMA) published a study examining the efficacy of both Lexapro, an SSRI, and problem-solving therapy in undepressed, recovering stroke patients.1 The study found that recovering stroke patients treated with either therapy or medication were less likely to be subsequently diagnosed with depression. After one year, 22% of the placebo group developed depression, while only 9% of the Lexapro group and 12% of the therapy group did. Following the study's publication there were numerous articles in the mainstream media extolling the benefits of the SSRIs. For instance, in USA Today, the lead author of the study stated: "I hope I don't have a stroke, but if I do, I would certainly want to be on an antidepressant."2 And as often happens after these types of studies, the media ask another expert to interpret the study. Fox News interviewed an expert psychiatrist from the University of Pittsburgh and reported that, "he hopes doctors will start prescribing preventive antidepressants to stroke patients."3 The expert said nothing about therapy. When we looked at the study, given that there was only a three percent difference between the results of therapy and medication, we were confused by a subtle but seemingly critical omission from the published paper. While the authors compared both Lexapro and therapy to placebo, they did not report on the direct comparison of therapy to Lexapro - surely of interest to those making treatment decisions, especially since every medication has the potential for adverse effects. In a letter to JAMA, we pointed this out. Five months later, our letter was published along with an acknowledgement from the original authors that indeed the difference between therapy and medication4 was not statistically significant. Since newspapers rarely reflect on their original coverage, the benefits of therapy for stroke patients will continue to remain a mystery to most of the news reading public. Journals such as JAMA require authors to publish their conflicts of interest at the end of their studies. In JAMA's conflict of interest policy they state that authors should include potential conflicts from the past five years. The study in question did list several conflicts, but the list did not include Forest pharmaceuticals, the manufacturer of Lexapro. During a subsequent internet search we were surprised to learn that four years previously the lead author had been listed on the speaker's bureau for Forest.5 The omission, however innocent or mistaken, is disturbing; neither the JAMA article nor subsequent media accounts noted that the lead author had served on the speaker's bureau for the manufacturer of Lexapro. However, disclosure of the relationship would not have changed the troubling end result: A researcher with a history of being funded by SSRI makers completes a 'gold-standard' federally-funded study of post stroke SSRI use, which is published in one of the most prestigious medical journals in the world, and is given a forum in the national media to tell the general public that anyone who has had a stroke, whether or not they have been diagnosed with depression, should start a prophylactic regimen of Lexapro ...even though non-medical approaches perform just as well. In addition to the lead author having an undisclosed conflict with the makers of Lexapro, a simple internet search also revealed that the expert who was subsequently asked to interpret the study for two different news outlets had been receiving money (https://mail.lmunet.edu/exchweb/bin/redir.asp?URL=http://www.psych.org/MainMenu/Research/DSMIV/DSMV/MeettheTaskForce/CharlesFReynoldsIIIMD.aspx) in the form of research grants from Forest since 2004, yet neither outlet reported his conflict. It is certainly true that having a conflict of interest does not automatically negate someone's view - even someone with a large conflict-of-interest can be correct. Yet, when facts emerge demonstrating that crucially important information was selectively omitted by researchers with conflicts-of-interests, it is hard to not question whether the conflict was the root of the problem. The medical community strives to make decisions based on evidence, but as this case illustrates we have unfortunately arrived at a point where taking the conclusions of clinical trials at face value is apparently a sign of naivette. Conflicts of interest may play an important role in the reporting of scientific findings. The problem is not limited to just a couple of isolated cases but involves the entire culture of medicine that has developed over the past ten years. Put bluntly, the scientific machinery is broken. There is no easy fix, but surely patients deserve better. References 1. Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. Jama 2008;299(20):2391-400. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://jama.ama- assn.org/cgi/content/extract/300/15/1757-b 2. Elias M. Study: Antidepressants help stroke victims. USA Today 2008. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://www.usatoday.com/news/health/2008-05-27-stroke- depression_N.htm 3. Reporter. Study suggests antidepressants for stroke victims. FOX News 2008. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://www.foxnews.com/printer_friendly_story/ 0,3566,358948,00.html 4. Lacasse J, Leo J. Escitalopram, problem-solving therapy, and poststroke depression. Jama 2008;300(15):1757-8; author reply 58-9. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://jama.ama-assn.org/cgi/reprint/300/15/1757-b 5. Robinson RG, Zorowitz RD. Pseudobulbar affect and stroke. Stroke: Clinical Update 2005;15(January/February 2005):1-4. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://www.stroke.org/site/DocServer/SCU_-_Jan- Feb_2005.pdf?docID=5161) Competing interests: None declared Note added at 0035 GMT on 6 March 2009 by BMJ after posting on behalf of the authors: We are fully aware that JAMA is concerned about conflicts of interest and has taken a leading role in promoting policies to benefit the medical community. We are pleased to report that we learned at the end of business on Thursday (3/5/09) that the JAMA Editorial Staff has looked into this matter and will be discussing it in the forthcoming March 11 issue.
Potential conflicts of interest: more information from JAMA 11 March 2009
Sharon Davies, letters editor BMJ Send response to journal: Re: Potential conflicts of interest: more information from JAMA	In a letter to JAMA published today (11 March 2009)[1] the lead authors of the study discussed by Leo and Lacasse in their rapid response[2] report and apologise for an incomplete financial disclosure for their study.[3] Dr Robinson details his involvement with Forest Laboratories and Pfizer, and Dr Arndt his ownership of Pfizer stock. They end by emphasising that, although Forest Laboratories provided honoraria and expenses through its speakers' bureau to Dr Robinson in 2004 and perhaps 2005, none of the design, analysis, and expenses of their study was supported by funding or any intellectual input from Forest Laboratories. 1 Robinson RG, Arndt S. Incomplete Financial Disclosure in a Study of Escitalopram and Problem-Solving Therapy for Prevention of Poststroke Depression. http://jama.ama-assn.org/cgi/content/full/301/10/1023-a 2 Leo J, Lacasse J. Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins. 5 March 2009. http://www.bmj.com/cgi/eletters/338/feb05_1/b463#208503 3 Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008;299(20):2391-400. Competing interests: None declared
Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins 20 March 2009
Steven N Wagner, Director of Litigation & Prosecution Citizens Commission on Human Rights International, Los Angeles, CA 90028 Send response to journal: Re: Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins	Jonathan Leo's and Jeffrey LaCasse's forthrightness and willingness to rock the medical boat, to go beyond the surface "authority" of the clinical studies that have become nothing more than a formality to "prove" the drug company's predetermined wishes, should be loudly applauded. And BMJ should be applauded as well for supporting the truth. Patients and the public need more Leos and LaCasse's in a world of "peer-reviewed" nonsense where too many peers are on the take from pharma. Thank you Drs. Leo and LaCasse for not letting psychiatrist Robert Robinson and JAMA just slide. Competing interests: None declared
NIH promotes the rise of merchant investigators. 22 March 2009
Richard G Fiddian-Green, FRCS, FACS None Send response to journal: Re: NIH promotes the rise of merchant investigators.	The NIH has, until very recently, promoted MD PhD types many of whom spend more time caring for rats than caring for patients and many of whom have never cared for a patient and even if they have are poor clinicians. Furthermore the grant system favours those investigators who have learned to milk the system, merchant investigators one might call them. Merchant investigators are to be distinguished from those clinicians who see a clinical need for a device and/or procedure, and need institutional and industry support to bring their ideas to fruition for the benefit of their patients. [It has proved a very frustrating process for me in the case of gastrointestinal tonometry, most of my ideas remaining undeveloped twenty yeasrs later]. It is hardly surpising, therefore, that healthcare in the US has become dominated by the merchant investigators and the pharmaceutical companies beating down their doors to acquire the rights to commercialize the latest magic bullets they naively believe they have discovered and patented. The cascade merchants one might call them. "Anti-angiogenic therapy offers great promise and is often used to treat cancer, either alone or in combination with chemotherapy" (1). Yet, as this opinion expressed in Nature reveals, it has not been as effective as Judah Folkman thought it might be in the case of VEGF for the response to treatment has proved to be so unpredictable, anti-angiogenesis therapy even promoting growth and spread of cancers in some instances. Monoclonal antibodies is another case in point. The longer term consequences upon immunity of, for example, inhibiting TNF are completely unknown. Indeed the clinical history of trying to neutralize the effects tetanus toxin has been disasterous and not nearly as effective as immunization with tetanus toxoid. The clinical potential for monoclonal antibodies directed against endotoxin [commericalized by Xoma and Centocor] might have been equally misguided a better solution being to have developed and vaccine against endotoxin. 1. Lee M. Ellis & David A. Reardon. Cancer: The nuances of therapy. Nature 458, 290-292 (19 March 2009). Competing interests: Patents issued in my name.
David and Goliath? 25 March 2009
Peter M English, CCDC Leatherhead, Surrey, KT22 7PL Send response to journal: Re: David and Goliath?	It would appear, if things are being accurately reported, that Leo and JAMA are taking on these roles, with the Leo being attacked by a bullying JAMA (which also appears to be trying to gag anybody who thinks they've identified a conflict of interest), but fighting back... See http://blogs.wsj.com/health/2009/03/23/jama-sets-new-policy-in- wake-of-disclosure-flap/ (and especially the comments) and http://online.wsj.com/public/resources/documents/leo_statement_for_WSJ.htm . Peter English. Competing interests: None declared
Re: Potential conflicts of interest: more information from JAMA 25 March 2009
Peter J Flegg, Consultant Physician Blackpool, UK Send response to journal: Re: Re: Potential conflicts of interest: more information from JAMA	JAMA have published an editorial "explaining" their position: http://jama.ama-assn.org/misc/jed90012pap_E1_E3.pdf Professor Leo's response is here: http://online.wsj.com/public/resources/documents/leo_statement_for_WSJ.htm Good on you, Professor. Competing interests: None declared
Stealth Advertising and Academic Stalking 30 March 2009
David O Antonuccio, Ph.D., Professor Psychiatry and Behavioral Sciences, University of Nevada School of Medicine, Reno, NV 89503, David Healy, M.D., Professor, North Wales Dept of Psychological Medicine, Cardiff University, Wales LL57 2PW Send response to journal: Re: Stealth Advertising and Academic Stalking	Stealth Advertising and Academic Stalking In their BMJ rapid response, Leo and Lacasse (2009) respectfully criticized an antidepressant study published in JAMA (Robinson et al., 2008) for ignoring that a psychosocial intervention was just as effective as an antidepressant for post-stroke depression and for failing to publish the authors’ relevant conflicts of interest. The editors of JAMA took it upon themselves to harass Leo and contact his superiors for his audacity (Armstrong, 2009). The rapid response by Leo and Lacasse (2009) and the ensuing dust-up with the editors of JAMA, highlight two important aspects of the current medical literature: (1) some studies in highly respected journals amount to stealth advertising that is probably more effective at marketing pharmaceutical products than the glossy ad on the facing page, and (2) when legitimate scientific critics respectfully point that out, they may be the recipients of what can only be described as academic stalking (Healy, 2008). The notion that negative data can get buried in a file drawer instead of being published in the medical literature has been around for over 30 years (Rosenthal, 1979). As the Leo and Lacasse (2009) piece illustrates, the problem may be worse than just burying negative results. It appears to also involve spinning negative results in a positive way and publishing them anyway. There is no better example than the case of the antidepressant literature, a literature replete with articles underwritten by industry with as many negative studies never published or published with a favorable spin as there are positive studies (Antonuccio et al., 2002; Antonuccio, Danton, & McClanahan, 2003; Kirsch et al., 2008; Turner et al., 2008). This effectively skews the literature on which clinicians rely to help their patients make informed choices about treatment options (Healy & Mangin, 2009). There are also many examples of scientists who have been harassed, bullied, or had their jobs threatened just for acting like scientists, because they stood up to the industry and refused to let data be buried or spun (e.g., Blumsohn 2006a, 2006b; Deyo, Psaty, Simon, Wagner, & Omenn, 1997; Healy, 2002; Healy, 2008; Lenzer, 2005; Lenzer, 2008; Marks, Swinson, Basoglu, Noshirvani, et al., 1993; Monbiot, 2002; Nathan & Weatherall, 2002; Rennie, 1997; Thompson, Baird, & Downie, 2001). But something has changed. Because of the internet, academic stalking is no longer in the shadows, giving consumers and other scientists a voice when they observe such behavior. And they are speaking loud and clear. Academic stalking is no longer acceptable. Consumers and independent scientists will not put up with it as evidenced by the scores of critical comments to the online Wall Street Journal health blog (http://blogs.wsj.com/health/2009/03/13/jama-editor-calls- critic-a-nobody-and-a-nothing/tab/comments/). Stealth advertising and academic stalking have led to the result that many patient volunteers generate research data that are never made accessible to the public, despite their sacrifices to participate and promises by researchers to promote science and the human good. For example, the Turner et al (2008) analysis of antidepressant trials found that 3449 depressed patients participated in studies that were never published. Another 1843 depressed patients participated in studies in which the data were published as positive in conflict with the FDA’s decision that they were negative studies. Someone should ask those patient volunteers if that’s acceptable to them. As we proposed in an earlier rapid response (Antonuccio & Healy, 2008), it is time for institutional review boards (IRBs) around the world, on behalf of the human subjects they are committed to protect, to demand internet accessible raw and summarized data from all approved scientific studies. This will allow consumers and the professionals who treat them to decide for themselves how to balance safety and effectiveness when choosing among treatment options. Patient volunteers deserve nothing less for their sacrifices. Antonuccio, D. O., Burns, D. D., & Danton, W. G. (2002). Antidepressants: A triumph of marketing over science? Prevention & Treatment, 5, Article 25. Available on the World Wide Web: http://www.journals.apa.org/prevention/volume5/pre0050025c.html Antonuccio, D.O., Danton, W.O., & McClanahan, T.M. (2003). Psychology in the prescription era: Building a firewall between marketing and science. American Psychologist, 58, 1028–1043. Antonuccio, D.O., & Healy, D. (2008). The researcher’s credo. British Medical Journal, 336, 629. Armstrong, D. (2009). Jama editor calls critic a “nobody and a nothing”. Wall Street Journal Health Blog, March 13, 2009, http://blogs.wsj.com/health/2009/03/13/jama-editor-calls-critic-a- nobody-and-a-nothing/ Blumsohn A (2006a). http://scientific-misconduct.blogspot.com/ Blumsohn A (2006b). Authorship, ghost-science, access to data and control of the pharmaceutical scientific literature: who stands behind the word? American Association for the Advancement of Science, Professional Ethics Report Vol XIX, 3; http://www.aaas.org/spp/sfrl/per/per46.pdf Deyo, R.A., Psaty, B.M., Simon, G., Wagner, E.H., & Omenn, G.S. (1997). The messenger under attack—Intimidation of researchers by special-interest groups, New England Journal of Medicine, 336, 1176-1179. Healy, D. (2002). Conflicting interests in Toronto: Anatomy of a controversy at the interface of academia and industry. Perspectives in Biology and Medicine, 45, 250-263. Healy D (2008). Academic Stalking and Brand Fascism. In Turk J, Thompson J Universities at Risk: How Politics, Special Interests and Corporatization Threaten Academic Integrity. Lorimer Press, Toronto, pp 108-137. Healy, D. & Mangin, D. (2009). Commentary: The once and future psychiatry. Academic Medicine, 84, 418-420. Lenzer, J. (2005). Researcher to be sacked after reporting high rates of ADHD. British Medical Journal, 330, 691. Lenzer, J. (2008). Contract research organizations: Truly independent research? British Medical Journal, 337, a1332. Leo, J. & Lacasse, J. (2009). Clinical trials of therapy versus medication: Even in a tie, medication wins. British Medical Journal, 338, b463. http://www.bmj.com/cgi/eletters/338/feb05_1/b463#208503 Kirsch, I., Deacon, B.J., Huedo-Medina, T.B., Scoboria, A., Moore, T.J., & Johnson, B.T. (2008). Initial severity and antidepressant benefits: A meta- analysis of data submitted to the Food and Drug Administration. PLoS Medicine, 5, 260-268. Marks, I.M., Swinson, R.P., Basoglu, M., Noshirvani, H, Kuch, K., O’Sullivan, G. & Lelliott, P.T. (1993b). Reply to comment on the London/Toronto Study. British Journal of Psychiatry, 162, 790-794. Monbiot, G. (2002). The fake persuaders: Corporations are inventing people to rubbish their opponents on the internet. The Guardian, May 14. http://politics.guardian.co.uk/green/comment/0,9236,715160,00.html Nathan, D.G. & Weatherall, D.J. (2002). Academic freedom in clinical research. New England Journal of Medicine, 347, 1368-1371. Rennie, D. (1997). Thyroid Storm. Journal of the American Medical Association, 277, 1238-1243. Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. (2008). Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA, 299, 2391-2400. https://mail.lmunet.edu/exchweb/bin/redir.asp? URL=http://jama.ama- assn.org/cgi/content/extract/300/15/1757-b Rosenthal R. (1979). The “file drawer problem” and tolerance for null results. Psychological Bulletin, 86, 638-641. Thompson J, Baird P, Downie J (2001). The Olivieri Report. James Lorimer & Co., Toronto. Turner, E.H., Matthews, A.M., Linardatos, E., Tell, R.A., & Rosenthal, R. (2008). Selective publication of antidepressant trials and its influence on apparent efficacy. New England Journal of Medicine, 358, 252-260. Competing interests: Competing interests for David Antonuccio: University of Nevada School of Medicine; Reno V.A. Medical Center; author of smoking cessation book Butt Out; past recipient of NIDA and NCI funding for smoking cessation research; past recipient (1995) of funding from Marion Merrill Dow for research on the nicotine patch; workshops on the treatment of depression; expert witness on depression or PTSD; private clinical practice. Competing interests for David Healy as of March 2008: In the past 10 years DH has had consultancies with, been a principal investigator or clinical trialist for, been a chairman or speaker at international symposia for or been in receipt of support to attend meetings from: Astra-Zeneca, Boots/Knoll Pharmaceuticals, Eli Lilly, Janssen-Cilag, Lorex- Synthelabo, Lundbeck, Organon, Pharmacia & Upjohn, Pierre- Fabre, Pfizer, Rhone-Poulenc, Roche, Sanofi, GlaxoSmithKline, Solvay In the past two years, DH has had lecture fees and support to attend meetings from Astra- Zeneca and Lundbeck. In the past ten years DH has been an expert witness for the plaintiff in 15 legal actions involving SSRIs and has been consulted on a number of attempted suicide, suicide and suicide-homicide cases following antidepressant medication, in most of which he has offered the view that the treatment was not involved. He has also been an expert witness in one patent case, and one securities case.
Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins 15 April 2009
Robert G. Robinson, Paul W. Penningroth Chair, Professor and Head of Psychiatry The University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242 Send response to journal: Re: Re: Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins	On 5 March 2009, Jonathan Leo, an Associate Professor of Neuroanatomy at the De Buse College of Osteopathic Medicine at Lincoln Memorial University, and Jeffrey Lacasse, an Assistant Professor of Social Work at Arizona State University, posted a letter to the editor on the British Medical Journal (BMJ) website stating that my failure to include Forest Laboratories in my financial disclosures indicated that “crucially important information was selectively omitted by researchers with conflicts of interest, it is hard not to question whether the conflict was the root of the problem.” Although I sincerely apologized to the editors and readers of JAMA for not accurately remembering the dates of 2 talks that Forest sponsored and 2 talks that Pfizer sponsored in my incomplete disclosure letter to JAMA,1 I want to set the record straight. As soon as this was reported to JAMA, Dr. Glass, the psychiatry editor, contacted me and I reviewed my old financial records and began the process of clarifying my disclosures to the readers of JAMA. I gave 2 talks over 2 days to local psychiatrists in Tucson, Arizona in the fall of 2004 for which I was paid by Forest Laboratories an honorarium of $1,500 for each talk plus $600+ for travel expenses. This amount of money is about what I would have earned if I had seen patients in our clinic for those 2 days. Since 2004, I have not received a penny from Forest Laboratories nor have I had any contact with anyone from Forest corporate headquarters. As I have repeatedly stated, the study published in JAMA2 on prevention of depression was entirely funded by the National Institute of Mental Health (NIMH). These kinds of trials are very expensive and, for 3 centers, we received in excess of half a million dollars per year for 5 years. Would any reasonable person construe this failure to disclose 2 talks in 2004 as intentional as Drs. Leo and Lacasse suggested? Leo and Lacasse also accused me and my co-authors of a “critical omission” from the published paper.2 They stated, “While the authors compared both Lexapro (i.e. escitalopram) and therapy to placebo, they did not report on the direct comparison of therapy to Lexapro.” The scientific method involves unbiased testing of hypotheses. As stated in our response to their letter to JAMA3 and in our article,2 we hypothesized that both escitalopram and Problem Solving Therapy (PST) would be superior to placebo, not that one would be superior to the other. Furthermore, this issue came up in the peer-review of our manuscript by Dr. Glass and 3 anonymous, but highly knowledgeable, reviewers. Their unbiased objective opinion was that the trial was not designed for head-to-head comparison, and therefore that the comparison should not be published. We also had to deal with the biostatistical challenge faced by every clinical trial; that is, how to deal with missing data of patients who failed to complete the study. Experienced biostatisticians involved in the review agreed that our publication should deal with this problem in 2 ways. The first was to use the Cox proportional hazards analysis with missing data censored (removed) at baseline. The other method was to assume that all patients who did not complete the trial would have been treatment failures (i.e. developed depression). Using the censored at baseline analysis, both escitalopram and PST were statistically significantly superior to placebo. When we used the treatment failure method, however, escitalopram remained statistically significantly superior to placebo, but PST was not superior to placebo. In our response to Leo’s letter to JAMA3 we used the censored at baseline method. If we had used the treatment failure method, the 2 treatments would not have been equivalent. One cannot help but wonder why Leo, a neuroanatomist, and Lacasse were so concerned about this head-to-head comparison. In fact, the title of their letter was “Clinical trials of therapy versus medication: even in a tie, medication wins.” Would any clinician conclude that from our published results? I think the answer seems to be that Dr. Leo may be on an ideologically based mission. He is a board member of the International Center for the Study of Psychiatry and Psychology (ICSPP). ICSPP was founded by Dr. Peter Breggin in 1971 and, according to their own website, it “has been informing the professions, the media, and the public about potential dangers of drugs . . . We have paid much attention to the fact that many psychiatric drugs though approved by the FDA have been shown to be neither safe nor effective. We are not against the use of psychoactive drugs by competent adults who have been fully advised of their value, potential side effects and the alternatives. However, we have often found that the diagnosing and prescribing of psychiatric medications often takes place in the false belief propagated by highly profitable drug companies that only good can ensue . . . We are highly in favor of voluntary confidential psychotherapy.” An acknowledgement by Dr. Leo that he is a member of the board of directors of ICSPP, that is strongly opposed to the blanket use of psychopharmacological treatments, it seems to me, should have been disclosed, particularly in light of his accusation that we made a “critical omission” from our published study.2 In this era of transparency, someone’s preconceived biases seem to me to be germane to reader’s interpretations of their public criticism of others. Finally, I have to wonder why the BMJ would publish the Leo and Lacasse letter. First of all, it appears that Dr. Leo, though under no strict duty to do so, did not inform them of his ideological agenda. It also appears that no one at BMJ checked with JAMA to see if an investigation or failure to disclose letter was underway? As a result, this letter triggered a chain of events which brought the issue to the public media. Bloggers, who knew nothing about the biases of the letter writers or about my relationship (or more accurately, lack of relationship) with Forest Laboratories, have publicly criticized me. I do acknowledge making, and subsequently, correcting a human error of not remembering when something occurred over a 5 year period. The Leo and Lacasse letter, however, has led to prejudgments before everyone involved has had an opportunity to respond. Perhaps our important professional and public debates about conflict of interest have been characterized by emotional response before full transparency has been achieved. 1. Robinson RG, Arndt S. Incomplete financial disclosure in a study of escitalopram and problem-solving therapy for prevention of poststroke depression. Jama 2009;301(10):1023-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19278945 2. Robinson RG, Jorge RE, Moser DJ, et al. Escitalopram and problem- solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008;299(20):2391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18505948 3. Robinson RG, Jorge RE, Arndt S. Escitalopram, problem-solving therapy, and poststroke depression reply. JAMA 2008;300(15):1758-9. Competing interests: During the past 5 years, I received payment from Forest Laboratories for 2 lectures in 2004 and from Pfizer for one lecture in 2004 and one in 2005. I also received payment from Avanir for presenting research and participation in one advisory conference in 2005 and 3 conferences in 2006 that the former Hamilton Pharmaceuticals sponsored. There was no financial support since 2006.
Conflicts Regarding Conflicts About Conflicts of Interest 17 April 2009
Jeffrey R. Lacasse, Assistant Professor, Arizona State University Phoenix, AZ, USA, 85003, Jonathan Leo Send response to journal: Re: Conflicts Regarding Conflicts About Conflicts of Interest	We appreciate Dr. Robinson’s response [1] to our own Rapid Response [2], and offer this letter of clarification. We can imagine that Dr. Robinson might feel personally attacked due to the media coverage of the issue, including that in the blogosphere, some of which was speculative in nature. This is regrettable, if beyond our control. We find Dr. Robinson’s research quite interesting, and share his concerns regarding the negative public health impact of poststroke depression. A careful reading of our original letter [2] will reveal that we did not write that Dr. Robinson intentionally concealed his conflicts of interest, as he states, and that we actually wrote “The omission, however innocent or mistaken, is disturbing…” We have no reason to disbelieve that a memory lapse was responsible for his non-disclosure in JAMA. Dr. Robinson raises an interesting issue regarding disclosure of conflicts-of- interests (COI). Medical journals require that authors disclose financial relationships. Ostensibly, this is because a large body of research demonstrates that physicians can be influenced through payments and gifts, even small ones, often without being aware of their acquired bias [3]. Admittedly, though, financial relationships represent only one source of conflicts-of-interest. Dr. Robinson raises the possibility that membership in certain organizations might also be considered COI. Specifically, he argues that Jonathan Leo is biased due to his past service on the board of the International Center for the Study of Psychiatry and Psychology (ICSPP). To clarify, both of us have served on the ICSPP board, although neither of us are currently (Jonathan Leo’s name was previously listed on the ICSPP website due to an administrative error). We are unsure whether membership in various organizations, or past service on boards, should be considered a COI that should be disclosed. Membership in such organizations is clearly different from a financial COI, in that the membership is based on common interests rather than remuneration. Should Dr. Robinson be required to disclose his membership in the American Psychiatric Association (or, for that matter, his 25 years of researching antidepressants in stroke patients) as potential COI? We do not think so. In support of the idea that Dr. Leo is ideologically motivated, Dr. Robinson quotes the ICSPP mission statement and writes, “Dr. Leo is on a board that that is strongly opposed to the blanket use of psychopharmacological treatments” [1]. In fact, we are both opposed to the blanket use of psychiatric medications, and favor their judicious, evidence-based utilization. We see little controversy in this statement and think most physicians would agree with it. The ICSPP mission statement also states, “We are not against the use of psychoactive drugs by competent adults who have been fully advised of their value, potential side effects and the alternatives.” We doubt that most physicians (or patients) would see the endorsement of such statements as being indicative of ideological bias. The reality is that ICSPP is an organization made up of clinicians and academics with a wide range of opinions on mental health issues, but who share a common concern about increasing medicalisation, the attendant use of psychotropic medications, and the influence of industry on the mental health field. Certainly, members of ICSPP are not alone in holding such concerns. Other researchers, clinicians, and journalists have expressed similar concerns [4-9], including the increasing use of psychiatric medication for a widening range of conditions. We study the promotion of psychiatric medications [10,11], and if our motivation is of interest, it was Dr. Robinson’s statements in the popular media that drew our attention to this issue. Dr. Robinson notes that, using the censored-at-baseline analytic method, escitalopram and problem- solving therapy were both superior to placebo; using the treatment-failure assumption, escitalopram was effective but problem-solving therapy did not separate from placebo. We certainly agree with Dr. Robinson that clinicians reading the article could understand it. Clinicians could report to their patients that escitalopram reduced the rate of depression, as did therapy using one type of analysis. Clinicians could also report that Robinson et al. found that 77.6% of placebo-treated patients poststroke patients did not develop minor or major depression [12]. In contrast, Dr. Robinson’s was quoted in the USA Today as saying, “I think every stroke patient who can tolerate an antidepressant should be given one to prevent depression," [13] a conclusion that Dr. Thomas Insel, the director of NIMH, publicly disagreed with. Based on these data, we, like Dr. Insel, are also are unconvinced that every stroke patient should immediately be administered an antidepressant. Regarding the head-to-head post-hoc comparison of escitalopram versus problem-solving therapy, we wrote to ask for this comparison [14], and Dr. Robinson responded in JAMA [15], reporting that there was no statistically significant difference between the two treatments. Now, in BMJ, Dr. Robinson reports that there are contradictory results using different methods of analysis. We are puzzled as to why this information was not simply published in the original reply to our JAMA letter. In terms of problem-solving and moving the field of academic medicine forward regarding COI controversies, there is a potential solution. As David Healy [16] has repeatedly suggested, authors should be required to make their raw data available to accompany the publication of their journal articles. Re-analyses could be performed immediately and COI could be seen as largely irrelevant, since it could be replaced by scientific discourse regarding data. The technology now exists for this to take place immediately. We suggest that this requirement, if implemented, could make discussions such as these obsolete. Importantly, it could ultimately result in an increase in the quality of care provided to patients. 1. Robinson RG. Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins. 15 April 2009. http://www.bmj.com/cgi/eletters/338/feb05_1/b463#211995 2. Leo J, Lacasse J. Clinical Trials of Therapy versus Medication: Even in a Tie, Medication wins. 5 March 2009. http://www.bmj.com/cgi/eletters/338/feb05_1/b463#208503 3. Brody H. Hooked: Ethics, The Medical Profession, and the Pharmaceutical Industry. Lanham, MD: Rowman & Littlefield Publishers, 2007. 4. Bass, A. Side Effects: A Prosecutor, a Whistleblower, and a Bestselling Antidepressant on Trial. Chapel Hill, NC: Algonquin Books of Chapel Hill, 2008. 5. Lane, C. Shyness: How Normal Behavior Became a Sickness. New Haven, CT: Yale University Press; 2007. 6. Barber, C. Comfortably Numb: How Psychiatry is Medicating a Nation. New York: Pantheon, 2008. 7. Horowitz AV, Wakefield JC. The Loss of Sadness: How Psychiatry Transformed Normal Sorrow into Depressive Disorder. Oxford University Press; 2007. 8. Healy, D. Let Them Eat Prozac: The Unhealthy Relationship Between the Pharmaceutical Industry and Depression. New York: New York University Press; 2004. 9. Diller, L. Running on Ritalin: A Physician Reflects on Children, Society, and Performance in a Pill. Bantam: New York, 1999. 10. Lacasse JR, Leo J, 2005 Serotonin and Depression: A Disconnect between the Advertisements and the Scientific Literature. PLoS Med 2(12): e392. doi:10.1371/journal.pmed.0020392. http://tinyurl.com/ccknms 11. Lacasse, JR, Leo J, 2009. Consumer Advertising of Psychostimulants: A Long Record of Misleading Promotion. Psychiatric Times, 26(2), e1-e2. http://www.psychiatrictimes.com/display/article/10168/1382819? pageNumber=1 12. Robinson RG, Jorge RE, Moser DJ, et al. Escitalopram and problem- solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA 2008;299(20):2391-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18505948 13. Elias M. Study: Antidepressants help stroke victims. USA Today 2008. http://www.usatoday.com/news/health/2008-05-27-stroke- depression_N.htm 14. Lacasse, J.R., Leo, J. Escitalopram, problem-solving therapy, and poststroke depression. JAMA 2008;300(15): 1757-1758. 15. Robinson RG, Jorge RE, Arndt S. Escitalopram, problem-solving therapy, and poststroke depression reply. JAMA 2008;300(15):1758-9. 16. Healy D. Our censored journals. Mens Sana Monographs 2008; 6(1): 244- 256. http://tinyurl.com/coahh5 Competing interests: Jeffrey R. Lacasse is a member of the Society for Social Work Research; Society for Community Research and Action; and a member of the management group for Healthy Skepticism Inc., an international non-profit organization dedicated to reducing harm from misleading drug promotion. He has previously served on the board of the International Center for the Study of Psychiatry and Psychology (ICSPP) from 2007- 2008. Jonathan Leo is a member of the Society for Neuroscience; the Association of Clinical Anatomists; an external peer reviewer of NICE guidelines for the treatment of ADHD; and a former board member for ICSPP.
Re: Conflicts Regarding Conflicts About Conflicts of Interest 24 April 2009
Laura S. Boylan, Clinical Associate Professor of Neurology New York University School of Medicine 10016 Send response to journal: Re: Re: Conflicts Regarding Conflicts About Conflicts of Interest	It was not obvious to me from the Robinson paper what the primary study endpoint was or that results were significant in the absence of a risk adjustment for history of mood disorders (1). In seeking clarification as to a priori definitions of study endpoints I went to the clinical trial registration at clinicaltrials.gov. The site includes an archive of all revisions. I was surprised to discover that no study endpoints were registered there until after the trial was over and the paper published. According to clinicaltrials.gov, endpoints were added in August of last year (2). JAMAs policy is that inadequately registered clinical trials are ineligible for manuscript review. Definition of primary and secondary endpoints is required and assurance of proper trial registration is described as an editorial responsibility. (3) Another problem is that while the study was funded in 2002 (4), the final disclosure published in JAMA covered a "five year reporting window" starting in September 2003, after the study was underway. The original study proposal funded by NIH involved four arms: nortriptyline, citalopram, psychotherapy and placebo. (4) By the beginning of the disclosure reporting period the two generic medications had been replaced by the newly launched Lexapro. JAMA and Dr. DeAngelis have been at the forefront of defining standards to enhance the quality, transparency and integrity of medical information (4,5,6). Clinical trial registration, guidelines for result reporting, and broad disclosures are all part of this effort. In the case of this particular paper, they appear not to have been adequately enforced. NIH should give a public accounting of study oversight and approval of protocol changes. 1. Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. Jama 2008;299(20):2391-400. May 28 2008 2. Clinicaltrials.gov archive for NCT0071643 http://clinicaltrials.gov/archive/NCT00071643/2008_08_20/changes Accessed 4/23/2009 3. DeAngelis CD, Drazen JM, Frizelle FA, et al. Is this clinical trial fully registered? a statement from the International Committee of Medical Journal Editors. JAMA. 2005;293(23):2927-2929. http://jama.ama- assn.org/cgi/content/full/293/23/2927 4. NIH CRISP database http://crisp.cit.nih.gov/ Accessed 4/23/2009. 5. Moher D, Schulz KF, Altman D; CONSORT Group. The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomized trials. JAMA. 2001;285(15):1987-1991. 6. JAMA Instructions for Authors http://jama.ama- assn.org/misc/ifora.dtl#ConflictsofInterestandFinancialDisclosures Accessed 4/23/2009 Competing interests: I am an active board member of Physicians for a National Health Program Metro NY, this organization supports single payer national health insurance or Medicare for All in the US. Issues specific to pharma are not a focus of their activities. I've been a member for years of nofreelunch.org a group run by Bob Goodman wherein doctors take a pledge not to take any gifts from pharma. I suspect my membership dues are behind. I teach the class on physician-pharmaceutical industry relations for med students at NYU. I was a member for many years of the formulary committee at Bellevue Hospital in NYC. I was on the task forces to establish policy for relations w/industry for medical student and graduate medical education at NYU. I am highly skeptical of the profit motive in healthcare and have written a number of letters to the editor of various journals on issues related to disclosure and conflict of interest and have written and spoken in public forums extensively on single payer health reform