Introduction: Dr. Nancy Olivieri’s Challenge to Deferiprone Licensing in Europe, 1999 to 2003
You can read an account of Dr. Olivieri’s challenge in Europe here. Abraham J, Davis C. European Law and New Health Technologies.
That challenge was ruled “inadmissible” – and was not heard after five years — on STANDING alone. This means that the MERITS of the case were not considered. This ruling, in essence, meant that commercial interests are the only ones which have a right to recourse to the European Courts. (Longer discussion to follow on this site).
The background to this is that in 1999 Dr. Nancy Olivieri learned that Barry Sherman (CEO, Apotex) had applied for licensing of deferiprone in Europe. Sherman’s application relied upon three clinical trials. Two of the three trials had been initiated by Dr Olivieri in Toronto in 1989 and 1992, respectively. Sherman had abruptly terminated both trials in 1996 after Dr. Olivieri raised safety concerns. The third trial upon which Sherman’s application for licensing in Europe relied was an Italian trial, which Dr. Olivieri, and her colleague Dr. Gary Brittenham, had designed and for which they had been the two Co-Chairs of the scientific oversight committee — before being removed by Sherman. Dr. Olivieri’s challenge to Sherman’s European licensing application opened at the European Court of Justice in Luxembourg in 2000. At that time Dr. Olivieri learned that she had been accused by Barry Sherman of committing research misconduct with respect to her trials. Based on this claim, Sherman had alleged to the regulator and court that Dr. Olivieri’s concerns about effectiveness and safety of deferiprone should be set aside.
Dr. Olivieri knew that she had not committed research misconduct. Professor Graham Dukes [LL.M.; MBBS; MD; former head of the Pharmaceuticals Programme of the WHO (Europe) in Copenhagen] was retained to conduct a formal audit on the pivotal trial (a RCT comparing standard therapy and the new drug) which Dr. Olivieri had initiated in 1992. Professor Dukes’ report is here. Appendix E-Dr.M.N.G.Duke’s Audit of Toronto Deferiprone Trials
Professor Dukes found: “Over half of the allegations relate to Apotex having failed to locate certain information … another substantial proportion result from a misreading of the protocol leading Apotex to conclude that certain tests were required where not, in fact, demanded by protocol. I conclude that the number of deviations from protocol was negligible, minor, and of no possible significance to the outcome and interpretation of the trial … not remotely such as to undermine what was throughout a conscientiously conducted study.” Professor Dukes’ conclusion was: “Such deviations as occurred are entirely trivial as compared to the grave suspicion of harm, and inefficacy, which began to emerge from the study of deferiprone while Dr. Olivieri was conducting it. It is therefore my firm conclusion that the allegations of Apotex regarding faults in the conduct of the study should be set aside.”
The Role of Gideon Koren, the University of Toronto and The Hospital for Sick Children in this long story (this is under development but here is a first, important document)
Dr. Gideon Koren was found guilty of research misconduct in one paper reporting the effectiveness and safety of deferiprone, the drug at the centre of this controversy. The Faculty Council Minutes of 22 April 2002 University of Toronto 2002-04-22 Faculty Council Minutes reveals a stirring defence of Gideon Koren by the then-Dean of Medicine at the University of Toronto, Dr. C. David Naylor.
Naylor’s pleas included: “Professor Koren has maintained an exemplary record….he has co-authored approximately 120 items 1999-2001 a publication output unmatched in the Faculty.” Despite the knowledge that Dr. Koren was guilty of research and professional misconduct, Koren retained his status and to our knowledge, no sanction was applied for his research misconduct. [For his sending of harassing hate mail and denying this authorship to a public inquiry, related but separate misconduct, Koren was given six months off, four with full pay.]
However, Gideon Koren’s paper was not retracted (full correspondence will follow on this matter) until 2019 notwithstanding the promise made by Dean Naylor in these Minutes. In other words, Koren’s paper, held to be research misconduct in 2002 was retracted only in 2019 after this investigation was launched following reportage in The Toronto Star: https://www.thestar.com/news/investigations/2018/12/16/sick-kids-orders-systematic-review-of-dr-gideon-korens-published-works.html
But then the promised investigation into (hundreds of) Gideon Koren’s other papers stopped. Koren’s license was removed, and he returned to Israel.
https://www.thestar.com/news/gta/2019/02/22/former-head-of-sick-kids-motherisk-lab-gives-up-medical-licence-amid-investigation.html
But why has the investigation into hundreds of his other papers not proceeded? More answers needed.