Here in the US, we’ve slowly become aware of how the pharmaceutical industry has stealthily penetrated the ranks of academic and organized psychiatry, fueling fundamental changes in our daily practice leading to soaring drug profits – but little or no change in our patients’ mental health. One of the prominent avenues for this industrial invasion has been journal articles authored by psychiatrists on the payroll of drug companies in one way or another – authors with clear conflicts of interest. Insistence on declarations of conflicts of interest has hardly solved the problem. All it has really done is make us more aware of how ubiquitous the problem really is. Declaring a conflict of interest may be better than having one and keeping it a secret, but that isn’t nearly as good as not having one in the first place. So the problem remains in epidemic proportions.
Right now, there’s a version playing out on the front pages in Australia involving Dr. Ian Hickie, executive director of the Brain and Mind Research Institute at the University of Sydney. It’s one that I’ve talked about here before [of sound and fury…, it’s about time…, long overdue…, a bad sign…, if you can’t do the time…]. This particular conflict is relevant because it speaks directly to the center of the problem – commercial interests influencing our scientific literature. And it’s an example of a notorious portal for such influences, a review article. We doctors like review articles because they summarize a lot of information and digest it for us – make things easier.
Melatonin analogues provide a new and efficacious mechanism for producing notable phase shifts in human beings. Although these drugs have been mainly studied for sleep disorders, they also have the potential to be used as primary or adjunctive drugs across a wider range of neuropsychiatric disorders characterised by persistent circadian disturbance. Importantly, only agomelatine [which also binds 5-HT2C receptors] has been reported to have clinically significant antidepressant effects. Because of its favourable adverse effect and safety profile, and the potential to help to restore circadian function between depressive episodes, this drug might occupy a unique place in the management of some patients with severe depression and other major mood disorders.
It’s not uncommon in my world to be engaged in very lively academic debates, like the risk versus benefits associated with new antidepressant drugs. Similarly, I have been widely attacked by a variety of vested health interests, particularly when I have argued for the clear cost-benefits associated with the range of new health initiatives.Basically, we reviewed a new drug class for treatment of depression, focusing on correcting abnormalities of the sleep-wake cycle. This is the type of depression that Andrew Robb has so bravely brought to the attention of the Australian community in recent years. Quite separately, however, some have alleged that we had not declared our financial or professional relationships with manufacturers of one of the compounds — even though we clearly stated these at the end of the original article. Importantly, the editor never raised potential competing interests as a major impediment before publication. This is an area where the local critics continue to defame me by misrepresenting this process. Some of the correspondents went on to assert that we did not provide an accurate review of the relative benefits or potential side-effects of one particular compound, agomelatine, claiming that we were biased by our previously declared interactions with the manufacturer. This unfounded allegation was repeated widely in the Australian and international social media, with links being forwarded to my university for consideration.
The content of the tweet is, in my view, clearly defamatory. Further, the journal has never provided a full account of its own role or the key dates over which interactions between us took place [July 2009 till May 2011]. Consequently, I have lodged a complaint with the Ombudsman of The Lancet with a view to seeking a full retraction of the editor’s defamatory public statements. Previously, a number of well known academics have not only contested the role that providing effective treatments for depression plays in reducing suicide but have actually objected to our work on the erroneous assertion that prescribing antidepressants markedly increases suicidal behaviour. More recently, our multicentre trial with colleagues from Australian National University evaluating a range of potential preventive treatments for depression in older people became a target. I was contacted by Jill Stark from The Age, who asserted that these same South Australian academics had labelled this trial “unethical”. No substantive grounds for that allegation were ever established.
Sadly, Horton’s intervention has given renewed life to this broader anti-psychiatry campaign in Australia. The campaign here is designed not only to discredit the legitimate use of medicines, those practitioners who provide effective treatments and the experiences of those who respond to treatment, it is also clearly designed to derail the current round of national mental health reform. As reported by The Australian on Monday, the activists are now calling on the Minister for Mental Health to remove me from the new National Mental Health Commission over either undeclared competing interests — which were clearly declared — or my poor standard of academic work.
In response to that highly relevant article — no tweet from Horton. Of course, no retraction of his previous adverse commentary on the standard of our work. As a colleague wrote to me yesterday: ”The editorial comments by Richard Horton, are at best disingenuous, considering he commissioned the review and had it peer reviewed. If his words are taken at face value, then it suggests that the editorial and peer review standards of his journal are not working.” Similarly, no public comment by our Australian colleagues on independent verification by The Lancet itself of the quality of our original academic work.
In recent times, he has become a real celebrity in the UK, due largely to the edgy nature of his tweeting [e.g. slamming the World Health Organisation] and his devotion to more politically correct campaigns on global health and development, mental health reform and the proposed restructuring of the UK health system. In my view, The Lancet, through the agency of Horton’s devotion to new media, is desperate to attract wider public attention before it goes out of business. From an armchair in central London, causing harm to individual academics, or a process like mental health reform in Australia, is a very minor concern.
We’ve been through all of this before too many times during the Age of Prozac and the Age of the Atypicals – spanning the last twenty-five years. It is unlikely that celebrity review articles will continue to be a viable motif for endorsing drugs. By now, it’s just too obvious, a tired and tiring genre – at least I hope it is. Psychiatry has been damaged more than we yet seem to know by this sort of blurring of boundaries between scientific discourse and commercial advantage, but our ranks remain replete with people who have thrived in a time when this kind of thing has been tolerated – a time when the pharmaceutical industry has, in return, financed a lion’s share of academic psychiatry and research.
I have a (black) dog in this race in that I was a subject in the US Phase III clin trial sponsored by Novartis (purchased the US rights from Servier) for sublingual agomelatine. I suffered a DILI a week after stopping the drug (I left the study early because of increasing symptoms 5 months into the 12 month open phase and after having completed the 8 week double blind placebo/drug phase). The for-profit CRO & the for-profit contracted IRB didn’t return calls until I left a voicemail with the words, “lawyer” and “state attorney general” in it. Then the CRO got interested enough to reimburse me for the hospital/MD office visit co-pays. And they decided to draw another set of liver enzymes, which thankfully, came back close to baseline normal. (A shock, I know). Nor would they put me in touch with Novartis. I still do not know if anyone reported the DILI to any agency (NIH or FDA). I did contact the MA Attorney General’s office, and the lawyer I spoke to was interested – not because of what happened to me, but because another lawyer in the office was serving as a subject in a clinical trial, and they wondered what the appropriate steps would be. So it seems as if no one has rasied the question before in this venue.
I have learned a whole lot about clinical trials as a result of participating in a few – some looked at biomarkers, and two were of phys. therapy for osteoarthritis pain and function – those are being done in the best manner imaginable – involved PI physician, informed support staff, excellent clinical controls, and f/u. I also participated in two looking at fMRI and tinnitus, and the investigator emailed me the findings and resultant poster presentation. These were done at academic medical centers, so maybe that’s a key difference.
But Dr. Nardo, your points about subject recruitment are more than accurate, from my n=1 experience. Most of the time, the screenings were done by front office receptionists, and it was pretty easy to ascertain what they were “looking for” in subjects. However, I also learned that many people get their healthcare entirely from serving as study subjects. Many, like myself, are unable to afford copays when they involve repeated/series of appointments or can find appropriate providers. But unlike myself, they allow themselves to be passively recruited, and they don’t/can’t do due diligence to read the literature, investigate the risk/benefits, and advocate adequately for themselves. Many of the studies did not include reimbursement except for parking validation, but others notably did.
How aggressively were subjects pursued in the agomelatine trials in the US? I don’t honestly know except in my case, the PI tried to steer me away from that trial and into an SSRI + antipsychotic combo drug trial (yes, that one). When I withdrew from the study, she and the subsequent PI both tried to sell me on more antidepressant drug trials – even with my DILI not fully resolved.
All this to wonder why Hickie isn’t addressing the withdrawal of ago by Novartis here. It barely passed muster in the EU. Why is Australia so enamored of it? And why is he championing it in spite of the evidence – as you cited, and of the US developments?
Yikes. What a story! For readers who don’t know what DILI is, see Drug Induced Liver Injury – an HHS White Paper.
“All this to wonder why Hickie isn’t addressing the withdrawal of ago by Novartis here. It barely passed muster in the EU. Why is Australia so enamored of it? And why is he championing it in spite of the evidence – as you cited, and of the US developments?”
I don’t know if Australia is so enamored, but Hickie is. He’s big on sleep research, sleep phases out of synch and maybe since the ‘blockbuster’ slot is empty, he’s got his eyes on it. It was a poor choice. Sleep phases are an interesting topic, sure enough – but he’s way jumped the gun with Agomelatine, and is trying his best to un-hear what the scientific community is trying to tell him right now…
As Jon Jureidini and I mentioned in our Lancet letter http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60097-X/fulltext Ian Hickie similarly promoted nefazodone (Serzone). Its manufacturer, Bristol Myers Squibb, provided funding for Hickie’s SPHERE mental health training program (for GPs) and ‘funding and the field force required to implement [an associated] clinical audit’ that found that ‘Sixty-three per cent of people attending general practice have some evidence of mental disorder’ http://www.ncbi.nlm.nih.gov/pubmed/11556438 Hickie also defended Serzone when evidence of liver toxicity emerged:
‘Clinical and research psychiatrist at the University of NSW, Ian Hickie, said reports of liver failure related to Serzone were cause for serious monitoring but were extremely rare.
“The issue about liver toxicity has been known for some time and that hasn’t precipitated a rush to withdraw it in Australia,” he said.
Dr Hickie also said the drug had a legitimate role as second or third line anti-depressant treatment for patients who were not responding to other drugs.’
http://www.theage.com.au/articles/2003/10/30/1067233296513.html
Then a SPHERE Newsletter put a positive spin on the withdrawal of Serzone from the Australian market in 2004, describing it as ‘a voluntary commercial decision because of its current low and declining rate of use’.
Dr Hickie’s personal and Brain and Mind Institute involvement with the Pharmaceutical industry is quite breathtaking. Most astonishingly, a “strategic medical education (i.e. Pharma marketing) agency Lifeblood (previously Educational Health Solutions) tied thus – Our partnership with the Brain & Mind Research Institute (inside which our Sydney office is based) provides us with unique access to some of Australia’s leading neuroscience clinicians and researchers. See http://www.lifeblood.com.au Re past “Lifeblood” activities see http://johnalchin.info/2012/02/13/time-for-ian-hickie-to-put-up-and-shut-up/ and http://www.theaustralian.com.au/news/health-science/gp-jaunts-boosted-drug-sales/story-e6frg8y6-1225890003658 Dr Hickie has very often been interviewed on psychiatric matters, and these involvements are never disclosed.
From (as noted, limited) Lancet disclosures “…drug industry partners (Wyeth, Eli Lily, Servier, Pfi zer, AstraZeneca)… served on advisory boards (for) nefazodone, duloxetine, and desvenlafaxine.” These are clearly MARKETING advisory positions, the research/clinical work fully completed prior to Australian industry involvement.
In particular the Lifeblood Pharma marketing connection WITHIN Brain and Mind Institute, as well as their involvement with SPHERE, GP “training”, Australian mental health environment and government policy generally ought be highly publicised. See http://www.lifeblood.com.au/capabilities/capabilities-more.aspx and see especially also http://johnalchin.info/wp-content/uploads/2012/02/Lifeblood.png – astonishing COI, unparalleled influence.
BIWX
Further to the ongoing saga with Hickie, there has been an article published on today’s Australian Doctor website:
Heavyweight clash: Hickie vs Lancet http://www.australiandoctor.com.au/heavyweight-clash-hickie-vs-lancet
Rob Purssey, it is not the case that Ian Hickie never discloses his pharmaceutical industry funding, but he very often does not. This December 2010 article declared ‘no conflicts of interest’ http://apy.sagepub.com/content/18/6/496.full. When pressed, Hickie subsequently disclosed links to Bristol-Myers Squibb and Pfizer, but only support for the project http://apy.sagepub.com/content/19/4/374.full No mention of Servier. Nor any mention of Bupa, despite being ‘Bupa’s Professor Ian Hickie’ http://www.agpn.com.au/__data/assets/pdf_file/0019/34291/20101129_ps_mh_november.pdf
Great apologies, my post wasn’t clear. In saying “very often been interviewed on psychiatric matters”, I meant by national radio, television, print media, on mental health service delivery matters, and in these popular press interviews “… these involvements are never disclosed.” (at least in my experience) It seems critically relevant to comments on ESP merits of psychological VS pharmaceutical treatments, on which Hickie speaks publicly often (albeit often implied) that he personally has extensive and ongoing commercial engagement with the Pharma industry spruiking their products, and that his Brain and Mind Institute also houses the very openly specifically psychopharm public relations firm “Lifeblood” which proudly states “Our partnership with the Brain & Mind Research Institute (inside which our Sydney office is based) provides us with unique access to some of Australia’s leading neuroscience clinicians and researchers.” It’s also hard to fathom how he can be placed in key Federal Govt committee positions advising on mental health policy matters with these extensive and ongoing conflicts. I don’t see them mentioned in the press in this regard either – and this IS of GREAT public interest.
Thanks for the white paper. I hadn’t seen it before – it is essential reading. Much appreciated.
I would like to contest your claim that the use of drugs has produced little or no change to the patients mental health. Some of these drugs can produce great change in the wrong direction. Antidepressants that cause mania and perhaps suicidality are just the start. Have you perhaps thought about some of the consequences on people’s lives?
Have you perhaps thought about some of the consequences on people’s lives?
Yes…