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?
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.
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.