This post is all about a marvellous article by Arthur Schafer on Conflict of Interest – or something like that. See below. But first some background.
In the Last Millennium
Over three decades ago, Toronto and Thalassemia came together in what became one of the most celebrated bioethical cases of any millennium that initially pitched Nancy Olivieri, Brenda Gallie and colleagues against Apotex, Gideon Koren and Toronto’s Hospital for Sick Kids.
Olivieri, then a junior haematologist, had the idea of running a trial of deferiprone, an orphan drug for thalassemia, and got the project to the point, where it needed industry support for possible licensing of the drug. An astonishing achievement for a young clinician and researcher.
Koren, a pharmacologist working in the same hospital, teed up Apotex, a Toronto based generic pharmaceutical company. As the work went forward, Olivieri became concerned that her baby was less effective and possibly more harmful than the standard treatment and voiced her concerns.
She began to get poisoned print letters. She and colleagues finally found that DNA traces on them revealed their author to be Gideon Koren, her supposed research colleague.
Koren didn’t get the chop. Apotex, the johnny come lately pharmaceutical company, who were by this point but not originally producing deferiprone, stood behind him not her. So too did the Hospital for Sick Kids.
Olivieri was hounded. Her crime was putting her duty to patients ahead of her duty to Apotex. She was fired on several occasions but, supported by the Canadian Association of University Teachers, she was reinstated each time when it became clear that Sick Kids hospital and Toronto university had breached procedures.
Ultimately Olivieri, Gallie and colleagues were vindicated in almost everyone’s eyes but Olivieri ended up having to move jobs while Koren remained in place.
An extraordinarily bitchy book by Miriam Shuchman – See The Drug Trial. – for a review of this book which portrayed Olivieri as the villain of the piece with Koren the hero and a small band of executives at the helm of Sick Kids Hospital as the only ones who could see the wood (a great pharmaceutical company) for the trees (patients).
Legal actions between Olivieri and Apotex continued for nearly a quarter of a century after the original events.
During this quarter century, Koren survived a further series of scandals, making his continued survival a mystery. Did he have something on the powers that be in Toronto? Was his research output – likely in part at least ghostwritten – too valuable to the university?
Death Drive?
So is this mythic story a case of repetition compulsion, Freud’s Death Drive, where a company like Chemie-Gruenenthal 40 years after first denying what most people think of as their pet drug, thalidomide, could cause horrific injuries kept on claiming it was good for this or that?
The Chemie-Gruenthals of this world always win – thalidomide was ultimately licensed in the USA and its derivatives made its backers (whoever they are) a fortune. On the basis of a degree of Nazi chic, with a twist in that it took in a close embrace of Israeli scientists and ex-Nazis, these derivatives right around the time Olivieri was first working on deferiprone become some of the most valuable pharmacological property on the planet .
But Koren was finally brought down. Perhaps the branch he was sitting on just broke from the sheer weight of stuff. His current whereabouts is a mystery. He’s in Israel but doing what and linked to who is less clear.
Barry Sherman, the owner of Apotex, also came a cropper recently, when in 2017 both he and his wife ended up dead in their indoor swimming pool – not from drowning – with seemingly no-one able to establish what has happened, despite huge amounts of money being put into both public and private investigations. Another enduring mystery.
Act 5
Just when you thought the Toronto and Thalassemia saga was beginning to resemble the final scenes from Hamlet, another twist to the plot has turned up.
As catalogued by Arthur Schafer in a compelling article, starting over a decade ago, the University Health Network hospitals in Toronto began running a “trial” of Apotex’s deferiprone against the standard (older) treatment deferaserox. What exactly this “exercise” was is unclear – UHN have variously called it a trial and research and denied it was anything of the sort.
The so called trial finished 5 years ago. Olivieri and colleagues applied for the data and a year ago Olivieri, Sabouhanian and Gallie published a paper detailing the outcomes of this trial – the only paper.
There was a saga getting access to the data in the first instance that is now complete with the publication of damning data.
If anything can be more damning than a hospital being linked to a set of predictable deaths, this case has it. Once the “trial” finished in 2015, no more patients appear to have been entered into the UHN deferiprone program. That might not sound a big deal but the difficulty as has been marvellously laid out by Arthur Schafer lies with the enquiries Olivieri and others made of the UHN system as to why this exercise was run in the first instance, why the results were not published, why the hospital all of a sudden stopped using the drug after 2015 without letting anyone it would seem know, and why faced with questions about what is going on do they continue to stonewall?
Arthur introduces the concept of institutional conflict of interest. I’m not a conflict of interest person ordinarily. My mind turns to ideas like repetition compulsion – but not of the Freudian sort.
Is the problem a deep-seated hatred of Olivieri and colleagues, or a lingering affinity for “Giddy” who mostly seemed a “good time guy”, or an affinity for someone else?
Why would another Toronto hospital go down this route, after Sick Kids sullied their reputation so badly, perhaps forever?
Why would the then President of the University of Toronto David Naylor, who had played an inglorious role in earlier disputes, when presented with the evidence of deferiprone’s harms, agree it indicated deferiprone was harmful but then wash his hands of any involvement.
Does the institutional conflict of interest lie in UHN or in Apotex or in some combination of Toronto medicine and Apotex? A lot of the evidence suggests that this trial was no accident but an organized, Sherman-directed campaign.
Can a monetary value be put on the conflict of interest? How many people in a hospital or university have to gain for the entire institution to end up conflicted? This is rather like the question of how many Germans need to be conflicted to give us a Hitler? Perhaps comparatively few.
What does it take to get a Miriam Shuchman to write a book like The Drug Trial?
The parallels between Apotex and Chemie-Gruenenthal are interesting. Neither company made the drug that they later seemed prepared to defend to the death.
In the deferiprone case the person most responsible for getting the drug to a point where it could be considered for use, Nancy Olivieri, warned about the hazards and has gone way beyond anything anyone could have reasonably expected of her or anyone to ensure that any use comes with warnings.
In the thalidomide case, the French researchers who made the drug, and later helped put it in German hands, have never spoken up – although there may be a trace. Almost no-one knows that Gruenenthal didn’t make it. This is one case where we need a ghost, as appeared to Hamlet, to reveal what happened.
Arthur’s is a must-read article. I’ve tried to leave the most sensational detail out of this post forcing anyone who has got this far to download Arthur’s article, read and share. There is a lot to be horrified by in what has gone on.
Olivieri and Gallie have set up an inthepatientsinterest website where many of the documents central to Arthur’s article can be found.
Any ideas on how best to explain what seems close to inexplicable are welcome.
Jewish people have a great record of tracking and bringing to book those who would rather not be recognised – here they are investigating Koren
Haaretz – Israel NewsMarch 30, 2020
Israel’s Maccabi Healthcare Provider Investigates Wrongdoing by Senior Doctor in Canada
Pediatrician and researcher Prof. Gidi Koren downplayed risks that could be caused by a drug he researched and ran unreliable tests for Canadian welfare authorities, organization Physicians for Human Rights Israel claims
The Maccabi healthcare fund is looking into allegations leveled by the organization Physicians for Human Rights Israel that one of its senior researchers, the pediatrician Dr. Gideon Koren, behaved unethically while doing research in Canada.
One of such instances of unethical behavior was research into a drug at Toronto University two decades ago, with the support of Apotex, the company that developed the medication. According to a report by a Toronto hospital with which Koren worked in the study, risks were discovered, but the drug company prevented notification to patients, in violation of professional and ethical obligations. According to Physicians for Human Rights Israel, Koren published findings that the drug was safe, and the company used his writings to push use of the drug. Physicians for Human Rights Israel notes that the hospital and university both took disciplinary action against Koren because of misconduct.
In a second incident exposed in 2017, The Star reported that in 1999, Koren wrote anonymous “poison pen” letters about a whistleblower colleague, Dr. Nancy Olivieri, sending them to his colleagues at SickKids and to the press, among other things calling her and her supporters a “group of pigs”.
Among the fallout is doubt shrouding no less than thousands of child protection decisions throughout Canada based on flawed tests for drugs and alcohol in hair from 2005 to 2015. The tests Koren used were not credible, other doctors have charged. A local Canadian court refused to allow a class action to proceed against him and the lab he led; Koren himself stated that the tests had not been the overriding consideration in the welfare authorities’ decisions and that most results were verified by other sources.
Pediatrician Dr. Gideon Koren, who is accused of unethical behavior
Pediatrician Dr. Gideon Koren, who is accused of unethical behaviorBat Sheva Koren
The suspicions against Koren, founder of the Motherisk and SickKids programs, were reported in Canada a year and a half ago, when The Star revealed that in a rare move, the College of Physicians and Surgeons of Ontario confirmed its investigation into Koren.
Sorry – I missed a chunk out of the above comment =re where he is working now
Haaretz – Israel NewsMarch 30, 2020.
Israel’s Maccabi Healthcare Provider Investigates Wrongdoing by Senior Doctor in Canada
Pediatrician and researcher Prof. Gidi Koren downplayed risks that could be caused by a drug he researched and ran unreliable tests for Canadian welfare authorities, organization Physicians for Human Rights Israel claims
The Maccabi healthcare fund is looking into allegations leveled by the organization Physicians for Human Rights Israel that one of its senior researchers, the pediatrician Dr. Gideon Koren, behaved unethically while doing research in Canada.
One of such instances of unethical behavior was research into a drug at Toronto University two decades ago, with the support of Apotex, the company that developed the medication. According to a report by a Toronto hospital with which Koren worked in the study, risks were discovered, but the drug company prevented notification to patients, in violation of professional and ethical obligations. According to Physicians for Human Rights Israel, Koren published findings that the drug was safe, and the company used his writings to push use of the drug. Physicians for Human Rights Israel notes that the hospital and university both took disciplinary action against Koren because of misconduct.
In a second incident exposed in 2017, The Star reported that in 1999, Koren wrote anonymous “poison pen” letters about a whistleblower colleague, Dr. Nancy Olivieri, sending them to his colleagues at SickKids and to the press, among other things calling her and her supporters a “group of pigs”.
Among the fallout is doubt shrouding no less than thousands of child protection decisions throughout Canada based on flawed tests for drugs and alcohol in hair from 2005 to 2015. The tests Koren used were not credible, other doctors have charged. A local Canadian court refused to allow a class action to proceed against him and the lab he led; Koren himself stated that the tests had not been the overriding consideration in the welfare authorities’ decisions and that most results were verified by other sources.
Pediatrician Dr. Gideon Koren, who is accused of unethical behavior
The suspicions against Koren, founder of the Motherisk and SickKids programs, were reported in Canada a year and a half ago, when The Star revealed that in a rare move, the College of Physicians and Surgeons of Ontario confirmed its investigation into Koren.
Related Articles
On Sunday, Toronto’s Hospital for Sick Children announced a review of all of Koren’s published work, The Star said, which reports its own investigation finding “what appear to be problems” in more than 400 of Koren’s papers.
The local probe in Israel ensued after the Physicians for Human Rights Israel organization urged the ethics bureau at the Israel Medical Association and the Maccabi management, in October, to investigate.
The Physicians organization called for that Koren’s work at Maccabi, including his guidance for researchers, to be terminated. “It is only proper that caution be exercised regarding a person who has fallen badly twice, and that he not be chosen for a position in which ethics, integrity and fairness are necessary conditions,” the Physicians for Human Rights Israel’s ethics chief Hadas Ziv wrote. The allegations focus on two issues in which Koren was involved.
Koren, 71, completed his medical degree in the 1970s and now lectures at a number of Israeli universities and volunteers at the Asaf Harofe medical center. He has been considered a global expert on toxicology and teratology, not least regarding fetal alcohol syndrome. He has published 15 medical books and over 1,700 papers. He also founded the Israeli band The Brothers & the Sisters, which was active from 1971 to 1983 and had a number of hits to its credit; he also wrote the children’s play “Fitz the Mouse”.
Koren commented that there is nothing to prevent him from engaging in research. “After the Olivieri report was published, I continued to hold senior positions,” he stated. Regarding the lab tests, he said that not a single child had been taken from its parents, or returned to them, based on the findings.
“The lab I headed was clinical, not forensic, and even won praise,” he said. He also claimed umbrage at the organization for “attacking without checking the facts” and said that claims of biased or misleading research were outright libel. Maccabi, commenting further to the letter it received some weeks ago, said a team is looking into the matter.
‘ The cases of Olivieri, Healy and Blumsohn illustrate this point.13 17 ‘ – Arthur Schafer
Thalassaemia major: the murky story of deferiprone
BMJ 2004; 328 doi: https://doi.org/10.1136/bmj.328.7436.358 (Published 12 February 2004)
Nancy F. Olivieri, MD, FRCPC
Professor of Pediatrics and Medicine
University of Toronto, Canada
I join my colleagues 30 in urging doctors and patients to examine
critically the data regarding deferiprone, with the help of individuals of
integrity and independence 45, 17, rather than to accept opinions
expressed in discussions at selected meetings (see 46.)
https://www.bmj.com/content/328/7436/358/rapid-responses
Review written by: Arthur Schafer
Nancy Olivieri is famous for raising doubts about an experimental drug with which she was treating thalassemia patients. Her principled stand, and the resulting scandal, led universities to offer researchers some protection against illegitimate drug company pressure. Medical journals changed their publication rules. Research hospitals changed their policies. She became an international icon
https://umanitoba.ca/faculties/arts/departments/philosophy/ethics/media/Drug_Trial.pdf
No one knows who did it or why, but everyone has a theory.
https://www.bloomberg.com/features/2018-apotex-billionaire-murder/
UKTS conducted its own campaign in favour of the FDA licensing of deferiprone.
We funded the research ourselves because no pharma companies were interested at the time. The money raised by the Society enabled Professor George Kontoghiorges to continue to develop the drug, working under Professor Victor Hoffbrand in his laboratory at the Royal Free Hospital. With the cooperation of clinicians Bernadette Modell and Beatrix Wonke, the Whittington Hospital in North London became a world leader in ground breaking thalassaemia treatment
USA thalassaemia patients celebrate the licensing of the oral chelator deferiprone –
https://ukts.org/wp-content/uploads/2019/11/issue119.pdf
Apotex sells global rights to deferiprone to Chiesi Group in carve-out transaction
https://www.lexpert.ca/article/apotex-sells-global-rights-to-deferiprone-to-chiesi-group-in-carve-out-transaction/
Now in other ‘hands’ …
My thinking is nothing new i guess but what seems to happen is that strong group bonds are encouraged to form with rituals and rewards By the time individuals realise mal practice taking place they have or feel they have in a sense colluded by benefiting from membership of the group ,which increases anxiety about speaking out or acting out. In medicine people are encouraged to form ‘clubs’ in different specialities and to act as rivals with other clubs, It’s meant that protecting their own turf for example has damaged both the NHS and their rivals social service I was invited to sit on a joint cttee once but left when I realised both parties together stitched up a strategy before meetings even began. Women as well as men, ‘leaders’ have been notable in encouraging other women to ‘network ‘to gain rewards conferred by cronyism and inauthentic loyalty, or ‘sucking up’ to the strongest group within their group. ,For that to happen it means making others ‘enemies’ rather than collaborators. When an initially naive lonewolf is perceived to signal ‘danger’ of some sort or the group is about to be ‘betrayed’ by breaching a code of silence – there are steps taken to take advantage of naive expectations that right action will take place by ‘leaders’ , When that doesn’t lead to silencing the person they will gather support from other groups to outlaw the one who in good faith imagined ethical behaviour underpins medicine in this case. The primary duty is to protect the professional group not the public or those who consult them. How often is the same spiel gushed after yet another scandal eg of baby deaths. The leaders of the packs usually don’t believe someone in an ‘inferior’ or weaker position could or would risk their wrath if they are exposed in wrong doing and it can get incredibly nasty to a point of no return. They are then unable to listen or try to collaborate or remedy things. Whats left is for anyone who can stomache pursuing a cause is to find their inner terrier and never take any expectations of ethical behaviour of any group for granted. Why in this case did the institutions in Israel appoint Koren when his back ground surely must be known to them ?
One of ‘our own’ …
A Furry Tale on Furry Tails …
The father of four also served as a medic in the Israel Defence Forces in the mid-1960s, as well as a year as a flight surgeon with the Israeli Air Force, according to the resumé.
https://www.yorkregion.com/news-story/5152481-inside-the-career-of-motherisk-founder-dr-gideon-koren/
Dr, Gideon Koren
Director at Motherisk Israel.
Senior Scientist, Maccabi-Kahn Institute of Research and Innovation and Ariel University.
https://www.isopisrael2019.org/prof-gideon-koren
In recent years, Koren and the hospital have come under media scrutiny for Motherisk’s support of the use of SSRI antidepressants during pregnancy
GSK acted responsibly, he says: “They ran to the government the minute they thought they saw something.
https://www.macleans.ca/society/life/theres-a-pill-for-that/
Apotex and the Paxil / Paroxetine Warning Label
https://www.baumhedlundlaw.com/prescription-drugs/paxil-injuries/apotex-generic-paxil-warning-label/
Professor Hoffbrand received the Sultan Bin Khalifa Grand International Thalassemia Award.
And so it all rumbles along …
… to the Death or Beyond …
Arthur Schafer
https://umanitoba.ca/faculties/arts/departments/philosophy/ethics/media/Let_Them_Eat_Prozac.pdf
Want to eliminate evidence of dangerous side effects from your new anti-depressant? First, ensure that company scientists design the experiment and tabulate the data before it is turned over to the university scientist whose name will grace the eventual publication. Better yet, when volunteers enrolled in the experiment become agitated (and potentially suicidal or violent) code them as “failing to respond to treatment”. Amazingly, by this simple sleight of hand, the alarming side effects entirely disappear. What isn’t recorded doesn’t exist. The respected scientist whose name goes on the ghost-written publication – a widespread practice, as Healy shows – seldom sees the raw data, and is happy to collect a generous fee from the company along with the status that comes with having “his” research published in a prestigious journal.
Leading drug industry figures play an unsavoury role in this story, but it cannot be said that the medical profession or government regulators emerge with armour shining. Those charged with protecting the public from unjustifiable harms seem not yet to have taken on board the central lesson of the 1962 thalidomide tragedy: All drugs are inherently risky. Only honest and well-designed research can tell us which drugs offer which patients the likelihood of more benefit than harm.
All over.
Bar a Whistle..
On 8 November 2019, the English Court of Appeal handed down judgment in favour of GlaxoSmithKline (GSK) on the permitted scope of the long-running Seroxat litigation.
https://www.addleshawgoddard.com/en/news/2019/court-of-appeal-judgment/
An alerter and copy of the Court of Appeal judgment can be found on the attached links.
https://www.hendersonchambers.co.uk/2019/11/11/court-of-appeal-dismisses-claimants-appeal-in-the-seroxat-group-litigation/
World news
Drug giant faces huge law suit
‘Prozac miracle’ could end in disaster
https://www.theguardian.com/world/2001/sep/06/medicalscience.businessofresearch
Sarah Boseley, health editor
Thu 6 Sep 2001
Concern over the potential for addiction of the SSRIs has been growing in recent years. Charles Medawar of the UK watchdog organisation Social Audit said: “I would think that the scale of the problem in the UK is comparable and I can’t see a lawsuit not happening here. I think people are extremely angry. It was obvious this was going to happen two to three years ago, but the Medicines Control Agency – the regulators – have done nothing to forestall it.”
The US lawyers allege that all the SSRI class of antidepressants have the potential to cause withdrawal reactions when people try to stop taking them, but that Paxil/Seroxat is the worst. The drug, which has the generic name of paroxetine, is at the top of a league table produced by the World Health Organisation which records complaints from 60 countries of bad reactions to medicines.
GlaxoSmithKline insists there is no problem with its drug. “There is absolutely no reliable scientific evidence that Paxil is addictive or leads to dependence,” said a spokesman.
He added: “As far as we’re concerned, all of the regulatory bodies are quite happy with the product.”
“I can’t see a lawsuit not happening here.” – Charles Medawar
“it cannot be said that the medical profession or government regulators emerge with armour shining.” – Arthur Schafer .