Oct 19, 2013, Toronto Star

In other countries, safety reviews of drugs are public. In Canada, they’re classified.

Bruce McKenzie would like to know how a controversial acne drug suspected of killing his healthy teenage daughter this year has, in Health Canada's words, "benefits" that "continue to outweigh the risks."
But the report that could explain how the federal agency arrived at this conclusion is a secret. It's one of more than 150 classified safety reviews completed by Health Canada this year alone.
While the U.S. Food and Drug Administration and the European Medicines Agency routinely publish details of post-market safety reviews of drugs as a basic accountability measure, Canada refuses, citing "confidential business information."
When the Toronto Star tried to access the report for the review of Diane-35, which is suspected of causing fatal blood clots in 13 young Canadian women, including McKenzie's 18-year-old daughter Marit in January, a reporter was advised to submit a request for the document through privacy legislation — a process that can take months to yield information, portions of which may be "blacked out."
"Safety information should not be confidential," said Barbara Mintzes, an assistant professor with the Therapeutics Initiative, a research centre that conducts systematic reviews of new drugs, at the University of British Columbia.
"There certainly is a question about whether this drug should still be on the market," said Mintzes, who has investigated Diane-35's use in Canada. "I would have been very interested to look at the report in detail to see the rationale. Do they actually have new evidence that it's more effective than alternatives for severe acne?"
Bayer, the company that sells Diane-35, told the Star it is "confident that healthcare professionals have the necessary information about our products to appropriately counsel and prescribe to Canadian patients."
Canada launched the review after France pulled Diane-35, also known as Dianette, from the market earlier this year. The French health regulator's investigation showed the drug was used primarily off-label as a birth control, despite repeated warnings to physicians.
The medication, which has been approved for use in Canada since 1997 as a last-resort, short-term treatment for severe acne, has been the subject of three safety advisories from Health Canada, warning physicians that patients who take it face an "elevated risk" of blood clots.
Some studies have shown those who take Diane-35 are four times more likely to suffer major clotting than women who are not on any kind of oral contraceptive. Other studies indicate the drug is twice as likely to cause clotting in women compared to other oral contraceptives.
Scott Sawler, director general of Health Canada's Marketed Pharmaceuticals and Medical Devices Bureau — the agency that determined Diane-35's benefits outweigh its risks in May of this year — would not say whether his reviewers investigated how the drug was being prescribed in Canada. He said the bureau is more concerned with how Bayer markets Diane-35.
"If we saw the company marketing it (as a birth control), we would certainly take action," he said. "If it is used outside its marketing authorization, it's a physician using it … off-label … and we know physicians do that."
Bayer said its product monograph "clearly states that Diane-35 should not be prescribed for the purpose of contraception alone."
Nearly 500,000 prescriptions were written last year in Canada for Diane-35 and its two generics — Cyestra-35 and Novo-Cyproterone/Ethinyl Estradiol — according to data supplied to Health Canada from IMS Brogan, a company that collects and analyses health care information.
Health Canada's adverse reaction database acts as a surveillance system for federally approved drugs. Members of the public and health professionals can submit complaints about suspected side effects. But because the system is voluntary and doctors are not required to file such reports, the database is underreported.
Health Canada warns the database "cannot be used on its own to evaluate a health product's safety profile."
While Bayer declined to comment specifically on Marit McKenzie's death, the company said it extended its "deepest sympathies to the women and their families who feel that they have been adversely affected by Diane-35."
A company spokesperson also noted by email that an adverse reaction report alone isn't direct evidence that the drug is to blame.
More than 165 serious adverse reactions have been reported to the database since 2000 that listed Diane-35 as the suspect cause. In the majority of these cases, the condition led to disability or hospitalization. Eight of the 13 women whose deaths are attributed to Diane-35 in the database were younger than 21. Most suffered severe blood clots affecting their legs, chests or brains.
"That's what we expected," said Sawler, who confirmed the database entries were examined as part of the review. He would not say what number of serious adverse reactions would trigger a red flag for Health Canada.
"A signal would be something going beyond what we expected," he said. "We anticipate a certain number of signals, a certain number of events with this product. That's what we've been seeing, less than we anticipated. The number of clots we expect is similar to the number of blood clots we would see with an oral contraceptive."
Marit McKenziedied in a Calgary hospital just days before Health Canada's Marketed Pharmaceuticals and Medical Devices Bureau reportedly began its review of the drug.
She had a bilateral pulmonary embolism — a massive clot blocking blood flow to both of her lungs.
A hospital pharmacist reported her death to Health Canada's adverse reaction database, listing Diane-35 as the suspect cause.
In late March, the death of a 15-year-old girl, who also suffered a fatal pulmonary embolism, was registered in the database. The entry cited Diane-35 as the suspect cause.
Two months later, Ottawa issued a brief statement on Health Canada's website, noting its review of Diane-35 was complete and that the benefits of the drug "continued to outweigh the risks when used as authorized."
Diane-35 is sold in 116 countries around the world, excluding the United States.

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