Drug fell short of company’s own threshold for effectiveness, analysis reveals..

Confidential industry data reveals a morning sickness pill taken by hundreds of thousands of Canadian women did not meet the company’s own targets for efficacy.

The drug is called Diclectin, a combination of vitamin B6 and a common antihistamine, and is recommended as a treatment for women suffering from nausea and vomiting during pregnancy. Canadian doctors write 300,000 prescriptions for Diclectin every year.

Yet when Toronto family doctor Nav Persaud reanalyzed the original data from a 2009 manufacturer-funded clinical trial, he could find no evidence the pill was effective. In fact, Persaud discovered the pill fell short of drug company Duchesnay’s own pre-established threshold.

“I have completely stopped prescribing this medication. I don’t think it should be prescribed. I don’t think patients should take it.” Persaud said.

His research on Diclectin started with a patient’s question: Does this pill work? With prescription pad in hand, Persaud realized he didn’t know, even though he’d been taught to give Diclectin to pregnant women if they were experiencing nausea and vomiting.

“I had been routinely prescribing the medication without thinking about it.”

When he checked the scientific literature, he couldn’t find data on Diclectin’s efficacy. So he made what he assumed would be a routine request to Health Canada for the information the agency has about the drug.

“If I’m a doctor who prescribes this medication, obviously Health Canada is just going to show me all the information about the clinical effect,” Persaud said.

He was wrong. The information was considered confidential business information and Health Canada refused to release it. That was in 2011.

7-year fight for data

For the next seven years Persaud filed access to information requests to both the U.S. Food and Drug Administration (FDA) and Health Canada with little success. But after Vanessa’s Law (Protecting Canadians from Unsafe Drugs Act) was passed in 2014, Health Canada agreed to show him the manufacturer’s 2009 trial data. But only after requiring him to sign a confidentiality agreement promising to destroy the documents.

As he sifted through the thousands of pages, he realized the company did not meet its own standard of proof. In the original study plan, it was decided the drug needed to show an improvement of three points on a symptom scale. But in the end, the difference between the drug and the placebo was less than one point — falling far short of the company’s target.

“So it’s clear the results of the study indicate the medication is not effective,” Persaud said.

Persaud is not the first to notice the weak evidence behind Diclectin.

The FDA approved the drug in 2013 but an internal review document notes “the treatment effect was small.” A Health Canada scientific advisory panel conducted a review of Diclectin in 2016  and noted the results of the study were “not definitive” and the clinical benefit of the drug was “unclear.” Still the committee did not recommend any changes to the drug’s label.

In an email sent today, Health Canada told CBC News: “The available evidence continues to support Diclectin in the treatment of nausea and vomiting during pregnancy.”

Duchesnay told CBC in a statement: “Both the safety and efficacy of doxylamine-pyridoxine have been proven in multiple cohort studies, meta-analyses, an ecological study and a neurological development study among others.”

Long history

Diclectin evolved from an old medication called Bendectin that was widely prescribed to pregnant women beginning in the 1950s. By 1979, there were two versions — the original U.S. pill and the Canadian version, Diclectin. The U.S. company, Merrell Dow Pharmaceuticals, stopped selling Bendectin in 1983 after a series of lawsuits claiming links with birth defects — a risk that was never proven. After many decades of use, Diclectin is considered to be safe.

Duchesnay says Diclectin has been used by 35 million women around the world.

Yet the company’s own data shows that no matter whether women took a placebo pill or the actual pill, they all felt better by the end of the two-week study. Persaud says both doctors and patients might assume the drug is the reason they got better, when in fact the condition improves on its own.

“If you’re a clinician and you prescribe it and women come back two weeks later and they feel better, what are you going to believe?”

Still, the Society of Obstetricians and Gynaecologists of Canada will continue to recommend the drug for morning sickness. And Health Canada has no plans to withdraw the licence.

Now what?

And Persaud expects little to change in the wake of his investigation.

“In an ideal world it would be removed because it’s proven ineffective. The reality is there’s lots of momentum to keep prescribing it.”

But should patients be prescribed a drug if there’s no evidence it works?  All drugs have some side-effects. With Diclectin, some women will feel drowsy from the antihistamine. And there’s also the cost — about $90 per month.

Steve Morgan, who studies pharmaceutical policy at the University of British Columbia, said one of the reasons for regulating drugs is to protect consumers from products that don’t work.

“Prescription drugs … are compounds that have the potential for both positive and negative impacts. If there is no proven benefit of a treatment, then there is no justification for exposing patients to risk of harm,” he told CBC News in an email.

Meanwhile, Nav Persaud is getting ready to start deleting files, as he is ordered to do under the terms of the confidentiality agreement Health Canada required him to sign. But he thinks other doctors should be able to look at the data and make their own decisions. So even as he deletes the files, he’s applied to Health Canada one more time for permission to make the documents public.

As for the patient who asked the original question?

“She didn’t take the medication and obviously she was right and I was wrong,” Persaud said. “I told her after she left I looked into it and that encounter has changed my practice and my whole approach to getting information about treatments.

“If that patient hadn’t questioned it, probably I would still be prescribing the medication today.”
Photo credit: Craig Chivers/CBC News

By Kelly Crowe, CBC News