1 Director, The Hospital for Sick Children Research Institute,
Chief of Research, The Hospital for Sick Children, Molecular and Medical Genetics,
University of Toronto,
2 Chief of Paediatrics, The Hospital for Sick Children,
Chairman of Paediatrics, Faculty of Medicine, University of Toronto
To the editor—We write to correct inaccuracies in your October
issue editorial and news article concerning the controversial clinical trial
involving Nancy Olivieri, The Hospital for Sick Children (HSC) and Apotex
Inc. Whereas there is no question that this case is complicated and that there
are as many interpretations of the facts as there are involved parties, the
allegation that the HSC administration "completely failed to support the efforts
of Olivieri" is false and the implication that we did not support Olivieri's
right to publish is unwarranted.
In a letter dated 24 May 1996, Apotex notified Olivieri (and her collaborator
Gideon Koren) that they would not renew the contract supporting the trial
of L−1 (Deferiprone). Apotex also warned Olivieri and Koren that they
would pursue legal remedies if they breached the obligations in their previous
three−year contract. In a letter dated 25 May, Olivieri and Koren informed
the hospital that they had already sought legal counsel, who had advised them
to contact the Canadian Medical Protective Association (CMPA). When Olivieri
subsequently met with university officials on 6 June, and with hospital representatives
on 18 July, she was represented by a lawyer from McCarthy Tetrault, the firm
retained by the CMPA. It was not until the hospital board of directors initiated
an independent external review that Olivieri requested legal assistance from
the hospital in this matter. Olivieri has been continuously represented by
lawyers from McCarthy Tetrault.
At the 18 July 1996 meeting, Olivieri and her lawyer requested that the
hospital take a position against Apotex, backing her scientific findings.
The hospital's opinion was that the conflict was a scientific dispute among
Olivieri, Koren, Apotex and several other scientists regarding the effectiveness
of L−1 and, as such, should be resolved through the scientific literature.
The hospital supported and encouraged Olivieri's initiative to submit her
findings for presentation at the December 1996 meeting of the American Society
of Hematology, which she did. She also reported her findings in an article
in the Medical Post (January 1997), in April 1997 at the Sixth International
Conference on Thalassemia and Hemoglobinopathies, and at the December 1997
meeting of the American Society of Hematology and in the
New England Journal of Medicine (
339, 417; 1998).
After Apotex did not renew the L−1 clinical trial contract, Olivieri
wished to continue to use L−1 to treat thalassemia patients at HSC and
Apotex agreed to provide the drug under the Canadian government's Emergency
Drug Release (EDR) program. Later, Apotex on several occasions contacted hospital
officials requesting that the hospital help them gain access to the data generated
while Olivieri treated patients under the EDR program, and HSC supported Olivieri
in refusing these requests. Olivieri's complaint that her data was used without
her permission was brought to The University of Toronto for adjudication (in
keeping with the university's Procedures to Address and Manage Scientific
Misconduct). An investigating committee was established and reported in
September 1997, dismissing the allegation and exonerating the faculty member
against whom the charge was made.
The connection between HSC and Michael Spino, now a vice president of Apotex,
should be clarified. Spino was a member of The Hospital for Sick Children
Research Institute for several years. When Spino began working for Apotex,
he left the staff of the hospital but became an unpaid consultant to HSC.
Since joining Apotex, Spino has not maintained a laboratory at HSC, but has
done collaborative research in Koren's laboratory. Koren and Spino co−supervised
a graduate student and a research technician. Spino was, and continues to
be, a professor at The University of Toronto.
Arnold Naimark, former dean of Medicine and President of the University
of Manitoba, has conducted a review to determine the facts and circumstances
of this complex case. We anticipate that his report will further clarify facts
in the case and make useful recommendations for future practice at the Hospital
for Sick Children. [As Nature Medicine went to press this report was
released and is available at
http://www.sickids.on.ca/HSCWeb/zReview/TheReview). Further− more, a second−phase review is also planned
to examine current hospital policies and procedures relating to the broader
issues of clinical trials and third−party funding. The outcome of these
reviews may also be of value to other institutions.
