1 Professor of Pediatrics and Medicine, University of
Toronto, Canada
2 Scientist, Medical Research Council of Canada
3 Director, Haemoglobinopathy Programs, The Hospital
for Sick Children and The Toronto Hospital
Olivieri replies—The facts of this case are quite straightforward.
The allegation that the Hospital for Sick Children (HSC) and the University
of Toronto "completely failed to support the efforts of Olivieri" is absolutely
true, as is the implication that it did not support my right to publish findings
about L−1 (Deferiprone).
Ultimately, the only support to me for legal protection came from the Canadian
Medical Protective Associa−tion (CMPA), an organization that serves
to protect physicians in Canada from legal threats arising in the practice
of medicine. The CMPA first limited its support to the issue of full disclosure
of the perceived risk of Deferiprone to my Toronto patients only. The CMPA
declined to support disclosure of perceived risks to patients in international
trials (of which I was the chair of the steering committee), to regulatory
agencies (to which applications were being made by Apotex for licensing, based
in large part on earlier work by us) or to the scientific community. Two months
after the abrupt termination of these trials by Apotex, I was unable to fulfill
these last three obligations without the risk of legal action by Apotex. The
Hospital nevertheless stated, unequivocally, that it would not provide legal
counsel for me in this matter. Written records of this refusal are available.
The HSC excused their action by saying it "...was a scientific dispute...."
This is alarming for an institution with a mandate to protect patients. In
the face of uncertainty over possible harm to patients, to do nothing is a
dereliction of a physician's duty by every international standard of ethics
in medical research. It is also illegal under Canadian criminal law. (Incidentally,
although we raised our concerns at a time when others were still enthusiastic
about the drug, we never requested that anyone at the HSC take a position
against Apotex, backing our scientific findings.)
The HSC Institutional Review Board had, in parallel with disclosure to
patients, recommended disclosure to regulatory agencies. This recommendation
was dismissed by the senior HSC administration, who stated that "the matter
could be settled without the help of regulatory agencies." Fortunately, the
CMPA, recognizing that I was "subject to the ethical obligations of a physician
as well as the obligations imposed by the Institutional Review Board, the
Declaration of Helsinki, and Medical Research Council of Canada's Code of
Conduct for Research Involving Humans," subsequently agreed to support disclosure
to the Canadian Health Protection Branch. Noting that I was "rightly concerned
about the safety and well−being of persons throughout the world," the
CMPA observed that such disclosure would be "in compliance with statutory
requirements." That I was able to submit and present data at scientific meetings
was solely the result of support ultimately provided by CMPA.
In January 1997, two abstracts endorsing the long−term effectiveness
of Deferiprone presented to a scientific meeting were co−authored by
Apotex−paid research fellows, a full−time employee of Apotex and
two University of Toronto investigators1,
2. These abstracts
and other subsequent communications3 continue to provide a favorable
interpretation of data arising from the Toronto clinical trials of Deferiprone
directed by me. The abstracts were submitted without my knowledge or consent,
or that of Gary Brittenham, whose NIH−funded laboratory generated these
data. An investigating committee at the University convened to investigate
this conduct ruled, incomprehensibly, that it is acceptable practice under
the current leadership of the Faculty of Medicine at the University of Toronto
for a scientist to publish NIH− and MRC−funded data without the
knowledge, consent or participation of the scientists who generated the data.
With regard to attempts by Apotex to gain access to data generated by me
and my colleagues—data that I repeatedly refused to provide them—Gideon
Koren, an Apotex−paid research fellow, gained unauthorized access to
my confidential patient files. This is well documented. The senior HSC administration
did not reprimand Koren or Apotex, but did advise me in writing that I should
refrain from informing patients whose charts had been accessed without authorization.
The name of Michael Spino, the vice president of Apotex, appeared on the
letterhead of the Division of Clinical Pharmacology at HSC as recently as
March 1998. Spino has confirmed that he maintained laboratory space at HSC,
a fact allegedly unknown by the director of the hospital's research institute.
Spino's technician confirmed in August 1998 that work on Deferiprone was still
ongoing in his laboratory.
Finally, as is now a matter of public record, the pursuit of a $20 million
donation by Apotex to the University of Toronto is the 'top' priority of the
University of Toronto.
Throughout 1997 and 1998, I and several other concerned scientists have
requested an independent inquiry into this matter. We have refused to participate
in Naimark's 'review' because of grave concerns about the fairness of a panel
appointed by one of the parties implicated in this controversy. Therefore,
presentation of the legal records, transcripts of tape−recorded messages,
other communications and unassailable facts that will not be presented to
Naimark will be included in a future full, independent and unbiased inquiry.
Tricta, F. et al. Long-term chelation therapy with the orally active iron chelator deferiprone in patients with thalassemia major. Proceedings of the 6th International Conference on Thalassemia and the Haemoglobinopathies, April, 1997.
Tricta, F. et al. Randomized trial of deferiprone (L1) and deferoxamine (DFO) in thalassemia major. Proceedings of the 6th International Conference on Thalassemia and the Haemoglobinopathies, April 1997.
Diav-Citrin, O., Atanackovic, G. & Koren, G. Correlation between initial hepatic iron concentration and response to deferiprone (L1) in patients with beta-thalassemia major. Clin. Pharm. Ther.192, PII-77 (1998).
