Nancy Fern Olivieri
Encyclopedia
Nancy Fern Olivieri, BSc
, MD, FRCPC, is a prominent Toronto
haematologist and researcher with an interest in the treatment of hemoglobinopathies.
She is best known for a protracted struggle with the Hospital for Sick Children
and the pharmaceutical company Apotex
about drug deferiprone
. Starting in 1996, Olivieri was part of a group conducting a clinical trial in order to evaluate the use of a drug in treating persons with a blood disorder, thalassaemia. During the course of the trial, Dr. Olivieri became concerned about evidence that pointed to the toxicity of the study drug and to the drug being inefficacious. Dr. Olivieri informed both the research ethics board that was monitoring the study and Apotex, the drug maker. The research ethics board instructed Dr. Olivieri to, inter alia, inform participants about her concerns. Apotex responded by noting that Dr. Olivieri had signed a confidentiality agreement as part of the drug trial and that informing participants about her concerns, the validity of which Apotex disputed, would violate that confidentiality agreement. Apotex threatened to vigorously pursue all legal remedies against her if she disclosed her conclusions to patients. Dr. Olivieri disclosed her concerns to her patients and Apotex ended the portion of the study that she was participating in.
Although Dr. Olivieri was admired for tenaciously defending research integrity and academic freedom, some critics characterized her as publicity-seeking and argued that she was wrongfully placed on a pedestal. Nancy Olivieri's scientific findings, which sparked the controversy, have been challenged worldwide, including her data, which suggested that deferiprone
led to progressive hepatic fibrosis, a finding which is disputed. Deferiprone
is currently licenced for use in over 50 countries around the globe, benefiting patients who need it, but not in Canada
and the United States
, possibly due to the North American media attention surrounding Dr. Olivieri.
An investigation revealed that one of Dr. Olivieri's critics, Dr. Gideon Koren
, had anonymously sent disparaging letters about Dr. Olivieri to the media and colleagues. Dr. Koren initially denied responsibility, but substantial DNA evidence tied him to the letters and he was reprimanded. In her 2005 book, psychiatrist and ethicist Miriam Shuchman pointed out that Nancy Olivieri's actions in preventing the drug from being developed in North America caused the death of a large number of children in Canada and the United States. Spokesperson for the University of Toronto, Professor David Naylor
, current president of the University and then Dean of the Faculty of Medicine and Vice Provost for Relations with Health Care Institutions, and others went on record regarding Olivieri's having "advanced 'demonstrably incorrect' allegations against others" and having used “hundreds of thousands of dollars of legal fees and services” from teachers' union funds, and then being “unable to admit she made a mistake.” Prof. Naylor also went on record citing the bias of CAUT and its Inquiry as having favored Olivieri and her Union and pointing to the lack of independence of both committees.
Dr. Olivieri has advocated for greater academic freedom
and called for less control of research by pharmaceutical companies. This situation was publicised extensively and was investigated by The Canadian Association of University Teachers
. Dr. Olivieri was awarded the 2009 AAAS Award for Scientific Freedom and Responsibility for her "indefatigable determination that patient safety and research integrity come before institutional and commercial interests and for her courage in defending these principles in the face of severe consequences."
On October 14, 2011, however, the basis for Dr. Olivieri's acclaim and the validity of her science were further called into question. On that date, based on further research which confirmed Dr. Koren's position, "the U.S. Food and Drug Administration approved Ferriprox (deferiprone) to treat patients with iron overload due to blood transfusions in patients with thalassemia, a genetic blood disorder that causes anemia, who had an inadequate response to prior chelation therapy... The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients...." This FDA approval further strengthens author Miriam Shuchman's claim that Olivieri's efforts to block the introduction of the drug led to the premature death of many youngsters with thalassemia.
On the contrary, the argument that “This FDA approval further strengthens author Miriam Shuchman's claim that Olivieri's efforts to block the introduction of the drug led to the premature death of many youngsters with thalassemia”, is severely weakened by Dr Sidney Wolfe’s (PUBLICCITIZEN) detailed letter (Oct. 12, 2011), to the FDA where he concludes. “…..given the lack of data from adequate and well-controlled clinical trials demonstrating the safety and efficacy of deferiprone, as well as serious questions raised by DSl's inspection of study LA01 regarding the integrity of clinical trial data presented to the FDA by the sponsor, we urge the FDA to reject approval of NDA #021825 for deferiprone…….FDA approval of deferiprone based on such inadequate data would indeed set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future”.
The FDA briefing notes associated with the decision reveal that the request for regular or normal approval for marketing of deferiprone was declined by the FDA following scientific review because the evidence presented in the Apotex New Drug Application failed to adequately demonstrate safety and efficacy. Also the FDA site inspection of Olivieri’s trials showed that Apotex had wrongly omitted or misrepresented 45% of the Olivieri data in its submission to FDA.
FDA then informed Apotex that additional satisfactory randomized controlled evidence and a full, detailed audit of the Olivieri trials were required if Apotex was to pursue regular approval. The company declined and instead pursued 'accelerated' approval (known as conditional approval in Canada and other jurisdictions), which requires the lowest level of evidence.
Conditional or accelerated approval usually occurs BEFORE there has been time for conclusive clinical trials to be completed on promising new drugs, not AFTER a 20 year drug development program has generated randomized, controlled evidence which fails to demonstrate safety and efficacy.
In the end, US FDA - FAST TRACK or "accelerated approval" for last resort treatment with deferiprone was based on a single arm, non-controlled, non-randomized retrospective re-analysis of 264 patients selected from 746 patients in pooled data from studies previously conducted, showing a 20% reduction in serum ferritin in 52% of patients, the clinical significance of which is uncertain. There was "a lack of data to verify absence of a mortality disadvantage when deferiprone is used over a long period of time". The further studies to which the company must commit as part of accelerated approval are not yet described.
Bachelor of Science
A Bachelor of Science is an undergraduate academic degree awarded for completed courses that generally last three to five years .-Australia:In Australia, the BSc is a 3 year degree, offered from 1st year on...
, MD, FRCPC, is a prominent Toronto
Toronto
Toronto is the provincial capital of Ontario and the largest city in Canada. It is located in Southern Ontario on the northwestern shore of Lake Ontario. A relatively modern city, Toronto's history dates back to the late-18th century, when its land was first purchased by the British monarchy from...
haematologist and researcher with an interest in the treatment of hemoglobinopathies.
She is best known for a protracted struggle with the Hospital for Sick Children
Hospital for Sick Children
The Hospital for Sick Children – is a major paediatric centre for the Greater Toronto Area, serving patients up to age 18. Located on University Avenue in Downtown Toronto, SickKids is part of the city’s Discovery District, a critical mass of scientists and entrepreneurs who are focused on...
and the pharmaceutical company Apotex
Apotex
Apotex is a Canadian pharmaceutical corporation. Founded in 1974, the company is the largest producer of generic drugs in Canada, with sales exceeding one billion dollars a year...
about drug deferiprone
Deferiprone
Deferiprone is an oral drug that chelates iron and is used to treat thalassaemia major.It has been licensed for use in Europe and Asia for many years while awaiting approval in Canada and the United States. On October 14, 2011, however, "the U.S...
. Starting in 1996, Olivieri was part of a group conducting a clinical trial in order to evaluate the use of a drug in treating persons with a blood disorder, thalassaemia. During the course of the trial, Dr. Olivieri became concerned about evidence that pointed to the toxicity of the study drug and to the drug being inefficacious. Dr. Olivieri informed both the research ethics board that was monitoring the study and Apotex, the drug maker. The research ethics board instructed Dr. Olivieri to, inter alia, inform participants about her concerns. Apotex responded by noting that Dr. Olivieri had signed a confidentiality agreement as part of the drug trial and that informing participants about her concerns, the validity of which Apotex disputed, would violate that confidentiality agreement. Apotex threatened to vigorously pursue all legal remedies against her if she disclosed her conclusions to patients. Dr. Olivieri disclosed her concerns to her patients and Apotex ended the portion of the study that she was participating in.
Although Dr. Olivieri was admired for tenaciously defending research integrity and academic freedom, some critics characterized her as publicity-seeking and argued that she was wrongfully placed on a pedestal. Nancy Olivieri's scientific findings, which sparked the controversy, have been challenged worldwide, including her data, which suggested that deferiprone
Deferiprone
Deferiprone is an oral drug that chelates iron and is used to treat thalassaemia major.It has been licensed for use in Europe and Asia for many years while awaiting approval in Canada and the United States. On October 14, 2011, however, "the U.S...
led to progressive hepatic fibrosis, a finding which is disputed. Deferiprone
Deferiprone
Deferiprone is an oral drug that chelates iron and is used to treat thalassaemia major.It has been licensed for use in Europe and Asia for many years while awaiting approval in Canada and the United States. On October 14, 2011, however, "the U.S...
is currently licenced for use in over 50 countries around the globe, benefiting patients who need it, but not in Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
and the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, possibly due to the North American media attention surrounding Dr. Olivieri.
An investigation revealed that one of Dr. Olivieri's critics, Dr. Gideon Koren
Gideon Koren
Gideon Koren M.D., FACMT, FRCP is a Canadian pediatrician, clinical pharmacologist, and toxicologist. Dr. Koren is also a noted composer of Israeli popular music.-Professional contributions:...
, had anonymously sent disparaging letters about Dr. Olivieri to the media and colleagues. Dr. Koren initially denied responsibility, but substantial DNA evidence tied him to the letters and he was reprimanded. In her 2005 book, psychiatrist and ethicist Miriam Shuchman pointed out that Nancy Olivieri's actions in preventing the drug from being developed in North America caused the death of a large number of children in Canada and the United States. Spokesperson for the University of Toronto, Professor David Naylor
David Naylor
Christopher David Naylor, OC, FRCPC, FRSC is a medical researcher and president of the University of Toronto.-Biography:...
, current president of the University and then Dean of the Faculty of Medicine and Vice Provost for Relations with Health Care Institutions, and others went on record regarding Olivieri's having "advanced 'demonstrably incorrect' allegations against others" and having used “hundreds of thousands of dollars of legal fees and services” from teachers' union funds, and then being “unable to admit she made a mistake.” Prof. Naylor also went on record citing the bias of CAUT and its Inquiry as having favored Olivieri and her Union and pointing to the lack of independence of both committees.
Dr. Olivieri has advocated for greater academic freedom
Academic freedom
Academic freedom is the belief that the freedom of inquiry by students and faculty members is essential to the mission of the academy, and that scholars should have freedom to teach or communicate ideas or facts without being targeted for repression, job loss, or imprisonment.Academic freedom is a...
and called for less control of research by pharmaceutical companies. This situation was publicised extensively and was investigated by The Canadian Association of University Teachers
Canadian Association of University Teachers
The Canadian Association of University Teachers is a federation of independent associations and trade unions representing approximately 65,000 teachers, librarians, researchers and other academic professionals and general staff at 120 universities and colleges across Canada.-Principal Aims:The...
. Dr. Olivieri was awarded the 2009 AAAS Award for Scientific Freedom and Responsibility for her "indefatigable determination that patient safety and research integrity come before institutional and commercial interests and for her courage in defending these principles in the face of severe consequences."
On October 14, 2011, however, the basis for Dr. Olivieri's acclaim and the validity of her science were further called into question. On that date, based on further research which confirmed Dr. Koren's position, "the U.S. Food and Drug Administration approved Ferriprox (deferiprone) to treat patients with iron overload due to blood transfusions in patients with thalassemia, a genetic blood disorder that causes anemia, who had an inadequate response to prior chelation therapy... The therapy is being approved under the FDA’s accelerated approval program, designed to provide patients with earlier access to promising new drugs followed by further studies to confirm the drug’s clinical benefit. The accelerated approval program allows the agency to approve a drug to treat a serious disease based on clinical data showing that the drug has an effect on an endpoint that is reasonably likely to predict a clinical benefit to patients...." This FDA approval further strengthens author Miriam Shuchman's claim that Olivieri's efforts to block the introduction of the drug led to the premature death of many youngsters with thalassemia.
On the contrary, the argument that “This FDA approval further strengthens author Miriam Shuchman's claim that Olivieri's efforts to block the introduction of the drug led to the premature death of many youngsters with thalassemia”, is severely weakened by Dr Sidney Wolfe’s (PUBLICCITIZEN) detailed letter (Oct. 12, 2011), to the FDA where he concludes. “…..given the lack of data from adequate and well-controlled clinical trials demonstrating the safety and efficacy of deferiprone, as well as serious questions raised by DSl's inspection of study LA01 regarding the integrity of clinical trial data presented to the FDA by the sponsor, we urge the FDA to reject approval of NDA #021825 for deferiprone…….FDA approval of deferiprone based on such inadequate data would indeed set a recklessly dangerous precedent for drugs reviewed under an accelerated approval process in the future”.
The FDA briefing notes associated with the decision reveal that the request for regular or normal approval for marketing of deferiprone was declined by the FDA following scientific review because the evidence presented in the Apotex New Drug Application failed to adequately demonstrate safety and efficacy. Also the FDA site inspection of Olivieri’s trials showed that Apotex had wrongly omitted or misrepresented 45% of the Olivieri data in its submission to FDA.
FDA then informed Apotex that additional satisfactory randomized controlled evidence and a full, detailed audit of the Olivieri trials were required if Apotex was to pursue regular approval. The company declined and instead pursued 'accelerated' approval (known as conditional approval in Canada and other jurisdictions), which requires the lowest level of evidence.
Conditional or accelerated approval usually occurs BEFORE there has been time for conclusive clinical trials to be completed on promising new drugs, not AFTER a 20 year drug development program has generated randomized, controlled evidence which fails to demonstrate safety and efficacy.
In the end, US FDA - FAST TRACK or "accelerated approval" for last resort treatment with deferiprone was based on a single arm, non-controlled, non-randomized retrospective re-analysis of 264 patients selected from 746 patients in pooled data from studies previously conducted, showing a 20% reduction in serum ferritin in 52% of patients, the clinical significance of which is uncertain. There was "a lack of data to verify absence of a mortality disadvantage when deferiprone is used over a long period of time". The further studies to which the company must commit as part of accelerated approval are not yet described.
External links
- Nancy F Olivieri, BSc, MD, FRCPC - University Health NetworkUniversity Health NetworkUniversity Health Network is a medical centre that comprises three teaching hospitals affiliated with the University of Toronto Faculty of Medicine....
Research. - Hemoglobal - a charitable organization Nancy Olivieri founded