Public Health

• Author: International Law Group

Dr. Nancy Fern Olivieri (applicant) is a Canadian physician and an internationally recognized specialist in the disease of thalassemia major (TM) (also known as Cooley's syndrome). [Editorial Note: Thalassemia is an inherited form of anemia caused by faulty synthesis of part of the hemoglobin molecule. It is difficult to treat.] The disease may affect as many as 20,000 EU citizens.

Starting in 1989, the applicant undertook to run a pilot study to test the effectiveness of deferiprone. This is an oral medication used to counter the iron overload that results from the frequent blood transfusions needed to treat TM.

Based on the results of that trial, the applicant got in touch with the U.S. Food and Drug Administration (FDA) about the requirements for getting deferiprone approved in the United States. Under the FDA's guidance, the applicant helped to draw up protocols for each of the required three clinical trials. The applicant was the principal investigator for two of the trials and co-chairman of the steering committee for the third trial. Apotex Research Inc., a Canadian firm, financed all three clinical trials, which began in April 1993.

At some point during the tests, Dr. Olivieri reached the preliminary conclusion that deferiprone was ineffective in nearly half of the patients treated. She reported her concerns to the Review Ethics Board of her employer, the Toronto Hospital for Sick Children, and to the relevant authorities. In May 1996, Apotex decided to end the applicant's involvement in the three clinical trials and to abort two of the trials.

The applicant then did a later study without the financial support of Apotex. She found evidence that deferiprone was toxic to the heart and liver and that its use increased the risks of premature death from cardiac disease or hepatic fibrosis. The applicant, therefore, immediately stopped using deferiprone on humans. She and others presented those findings in an article at 339 New England Journal of Medicine 417 (Aug. 1998).

In February 1998, Apotex applied to the European Agency for the Evaluation of Medicinal Products (EMEA) for an EU marketing authorization under Article 4(1) of Regulation No. 2309/93 for Ferriprox, the active ingredient of which is deferiprone. Apotex also sent the reports from the three clinical trials of deferiprone, but the documents lacked Dr. Olivieri's signature. The EU Committee for Proprietary Medicinal Products (CPMP) formulates the opinions of the EMEA. In...