Andrew Francis Wallace/Toronto Star
The pregnant patient sitting in Dr. Nav Persaud’s downtown Toronto clinic had questions about a routine prescription.
He gave a quick, reassuring answer, but after she left, Persaud wondered if he really knew enough about the drug.
A few weeks later, he asked Health Canada for all of the information it had on Diclectin, a popular pill taken for morning sickness endorsed by Sick Kids’ Motherisk and another medical organization.
The information, he thought, could help him make a more informed prescribing decision in the future.
What he got instead was a three-and-a-half-year runaround from the regulator and more than 200 censored pages.
This is not a story about a drug’s safety. This is a story about secrecy.
“It is outrageous that Health Canada is keeping this information from a family doctor like me,” Persaud said. “This shows that it is practically impossible for a doctor to get information from Health Canada — even for a drug that is commonly prescribed to pregnant women.”
When it comes to transparency on the subject of prescription drugs, the Star has found drug companies in Canada have influence over what information can be released to the public.
In this case, Health Canada was required to consult the morning sickness drug’s maker, Duchesnay, to help decide what should be kept from the doctor because it was deemed confidential business information.
And despite new drug safety legislation that empowers the health minister to disclose this kind of information to a doctor in some cases without a drug company’s permission, Health Canada says it is consulting with stakeholders on the issue, and further regulations may be required to define how and when this power is used.
Persaud’s quest for information about Diclectin, which combines an antihistamine and vitamin B6, began Sept. 6, 2011, with Access to Information Request No. A-2011-00688.
He heard little until six months later, when a Health Canada staffer told him by email that the regulator was “negotiating with the third party on which records they wish us to protect.”
In this case, the third party was Canadian drug maker Duchesnay.
Access to information law requires the government to consult with third parties, such as companies, when it intends to release a record that might contain confidential business information and when that information is owned or was supplied by the third party.
Finally, more than a year after his initial request, Health Canada provided Persaud with some information on Diclectin. Of the 359 pages provided, 212 were completely censored and other pages had blacked-out sections under titles such as “Adverse Events,” because they were deemed confidential business information.
Health Canada has refused to detail what information, if any, Duchesnay wanted hidden from Dr. Persaud. The company said it could not comment on Access to Information requests filed to the government about its products, but added that the only information it does not consider public is “proprietary information or intellectual property, such as manufacturing processes and stability testing data.”
“It is absurd that the pharmaceutical company that sells Diclectin gets to negotiate in secret with Health Canada about what information will be disclosed to a prescribing doctor,” Persaud said. “I believe that people would prefer to receive information about a medication from a source that is completely independent of the company that sells the medication.”
Meanwhile, the Star has also learned that Diclectin maker Duchesnay has or has had financial ties to both the Motherisk program at the Hospital for Sick Children and the Society of Obstetricians and Gynaecologists of Canada.
All three refused to detail for the Star the sums donated by the drug company.
While Persaud waited for the government to release information, he started doing his own research. Without the help of Health Canada, he and two colleagues concluded that while the use of antihistamines such as Diclectin is not associated with significant safety risks, their benefit in the treatment of morning sickness had been overstated by research affiliated with Motherisk.
Diclectin was approved for use in Canada in 1983. It has been recommended by both Motherisk’s counselling centre and as the “standard of care” by the Society of Obstetricians and Gynaecologists of Canada. Doctors rely on these recommendations when making prescribing decisions.
“I tried to obtain every study about the medication, as I think my patients would expect all of the evidence to be considered,” said the Toronto doctor, who also teaches at the University of Toronto and researches drug safety and other health-care issues for the Li Ka Shing Knowledge Institute at St. Michael’s Hospital.
Supporting the drug’s recommendation was a 1997 study co-authored by Dr. Gideon Koren, founder of Sick Kids’ Motherisk, a program that, among other things, counsels pregnant women on medications. The “meta-analysis” boasted that it included 24 studies of antihistamines involving more than 200,000 pregnant women, giving it an “unprecedented power to reject” any concern that antihistamines might cause birth defects.
The study also suggested the use of antihistamines could actually reduce the chance of birth defects.
The results were often cited in places ranging from medical articles to the Canadian clinical guidelines that advise doctors to prescribe Diclectin to treat morning sickness.
The guidelines are written by the Society of Obstetricians and Gynaecologists and specifically cite Koren’s 1997 study when saying that “data have shown a slightly reduced incidence of major and minor malformations with first trimester exposure to various antihistamines.”
Persaud said the 1997 study overstated the benefits and that other treatments can be just as effective.
In September 2013, he and his colleagues had their re-analysis of the 1997 Motherisk study published in a U.S. medical journal. The 1997 study, they found, had significant flaws: it overstated the number of participants by tens of thousands and inaccurately suggested that antihistamine use is associated with a decreased risk of malformations.
Motherisk’s Koren spoke to the National Post when Persaud’s critical analysis was published. According to the Post, he “acknowledged that there were some mistakes in the citation of data in the study and its estimate of how widely Diclectin has been studied.”
He insisted that all the evidence shows Diclectin is safe and effective, and denied he had been swayed by Duchesnay’s funding of Motherisk.
Months later, in a “Motherisk Update” published in Canadian Family Physician, Koren and two co-authors said Persaud’s analysis was “erroneous.” Persaud said he stands by his work.
In another scientific journal article, a commentary published last year, Persaud and his co-authors called for a reconsideration of clinical guidelines that recommend Diclectin as a first-line treatment for morning sickness. It also said that there is “no clear evidence” that the drug is more effective than vitamin B6 alone.
Koren did not respond to requests for interviews for this story, and neither Motherisk nor Sick Kids responded to the Star’s questions about the 1997 study.
Duchesnay says the drug’s safety and efficacy has been clearly established through numerous studies by well-respected researchers over the past 30 years. “Duchesnay focuses on the development of effective remedies that are safe for pregnant women and their unborn children,” company spokesman Ron Vaillancourt said.
A spokesperson for the obstetricians society said the drug is safe and told the Star that its “clinical guidelines on nausea in pregnancy are currently being updated and will be published in the coming months.”
Persaud’s research, suggesting that other medications may be just as effective, raises the question of whether the popular Diclectin tablets, emblazoned with the silhouette of a pregnant woman, should be the first thing doctors turn to when treating morning sickness.
It also underscores the importance of Health Canada being transparent with doctors.
“This isn’t proprietary information. It’s clinical information. At the end of the day, you wouldn’t have it but for people giving up their bodies in research trials,” said Matthew Herder, assistant professor at Dalhousie University’s Faculty of Medicine.
Three-and-a-half years have passed since Persaud asked Health Canada for all the information it had on Diclectin.
In March, Persaud re-requested the full, uncensored 359 pages of Diclectin information. He made this request of Health Canada and Health Minister Rona Ambrose, who can, under the new drug safety legislation, in certain cases disclose confidential information about a drug without a drug company’s consent.
For weeks he got no response.
The Star then asked the country’s health regulator questions about Persaud’s request. The doctor received a call three days later.
At first, he said, he was told by a Health Canada staffer that he would get the information within days. But signals at the regulator seemed crossed, because Persaud got a followup email from Health Canada saying a “third party” would again have to be consulted before any information is released.
Earlier this week, Persaud got another call, and again he was told information was coming soon.
It has not arrived.
Health Canada told the Star it is reviewing Persaud’s file to ensure all relevant records were released to him.
“Physicians are the ones who are responsible for digesting clinical evidence and making recommendations, not regulators,” Persaud said. “Health Canada should never keep that information from clinicians.”