A commonly prescribed drug to treat nausea and vomiting in pregnant women is not effective, according to a new paper that analyzed previously unpublished information about a years-old clinical trial.
Researchers in Toronto and Ottawa obtained documents from Health Canada about the randomized clinical trial reported in 2010 as showing that pyridoxine-doxylamine, sold in Canada under the brand name Diclectin, was effective in reducing nausea and vomiting in pregnancy.
Using a 13-point scale, the trial found that women who took the drug reported improvements in their symptoms that were 0.7 points greater than improvements among women who took a placebo.
But according to Dr. Nav Persaud, the lead author of the paper, a report from the drug鈥檚 manufacturer said the trial findings would only be clinically important if there were a three-point reduction in symptoms among women who took the medication.
That 鈥渆xpected difference鈥� of three points was not made public before now, said Dr. Persaud, a Toronto family physician who has been digging up information about Diclectin for years. He said it was also missing in the original published paper about the clinical trial, which was conducted at six university medical centres in the United States.
The findings were based on the outcomes of 101 women who took pyridoxine-doxylamine and a control group of 86 women. The original enrolment in the clinical trial was higher, but many women dropped out. By the end of the two-week trial, most women who took the placebo had little or no symptoms. The trial was sponsored by Duchesnay Inc., the Quebec-based manufacturer of Diclectin.
Dr. Persaud鈥檚 latest analysis of thousands of pages of Health Canada documents about Diclectin, obtained under drug transparency legislation called Vanessa鈥檚 Law, was published
The paper concludes that there is no 鈥渃linically important benefit鈥� of taking Diclectin to help alleviate nausea and vomiting during pregnancy.
鈥淚t is quite likely that the women who took this medication when it was prescribed to them 鈥� were getting better because of the natural course of nausea and vomiting, and their improvement likely had nothing to do with the medication,鈥� said Dr. Persaud, who has stopped prescribing Diclectin in his own practice.
In light of the re-analysis of the clinical trial, Dr. Persaud believes that Health Canada should revisit its stance on Diclectin, the only prescription drug authorized by the government agency to treat nausea and vomiting in pregnant women.
On Wednesday, Dr. Persaud wrote a letter to the agency, formally requesting it conduct a review of the medication -- a review which he believes is 鈥渞easonable, important and perfectly aligned with Health Canada鈥檚 purpose.鈥�
鈥淚 think that once a medication is approved, (Health Canada鈥檚) decision is not revisited unless there is serious concern about the safety of the medication,鈥� Dr. Persaud told CTVNews.ca in a telephone interview.
鈥淐learly we need a more efficient, collaborative way of doing this,鈥� he said of the way medications are tested, approved and prescribed in Canada.
But in a statement to CTVNews.ca, Health Canada said 鈥渢he available evidence continues to support Diclectin in the treatment of nausea and vomiting during pregnancy.鈥�
A Health Canada spokesperson said the agency reviewed the latest available safety and efficacy data on Diclectin in 2016. That review, which included advice from an external panel, also included discussion about the clinical trial Dr. Persaud and his colleagues re-analyzed.
鈥淣o new safety or efficacy issues were identified as part of the review,鈥� Health Canada said. The summary of its Diclectin safety and efficacy reviews
Health Canada also said its position is 鈥渃onsistent with that of other regulators,鈥� including the U.S. Food and Drug Administration, which approved the drug in April, 2013 under the brand name Diclegis.
The manufacturer Duchesnay Inc. said the drug has been prescribed for more than 40 years in Canada 鈥渁nd has been repeatedly proven safe and effective for use throughout pregnancy.鈥�
In a statement to CTVNews.ca this week, a company spokesperson said the clinical trial referenced in Dr. Persaud鈥檚 latest research paper 鈥渨as designed and developed in collaboration with the FDA through a special protocol assessment.
鈥淭he clinical trial achieved a statistically significant endpoint using the method of analysis requested by the FDA in accordance with all FDA requirements,鈥� Fiona Story said.
She also said the safety and efficacy of doxylamine-pyridoxine have been proven in 鈥渕ultiple cohort studies, meta-analyses, an ecological study and a neurological development study, among others.鈥�
Dr. Persaud has long questioned the widespread use of Diclectin. In another paper published a year ago, Dr. Persaud and co-author Rujun Zhang looked at the never-before-published results of an older clinical trial from the 1970s and concluded that data also called into question the benefits of Diclectin.
Shortly after that paper was published, the Canadian Family Physician journal said it agreed with Dr. Persaud that there is no clear scientific evidence behind the recommendation to use Diclectin as a 鈥渇irst line鈥� of treatment for nausea and vomiting in pregnant women.
Dr. Persaud also called for changes to guidelines on Diclectin four years ago, after he discovered that , despite previous research claims.
However, the Society of Obstetricians and Gynaecologists of Canada Diclectin as a 鈥渇irst line鈥� of treatment for nausea and vomiting during pregnancy due to its 鈥渆fficacy and safety.鈥�
Carol Charles, who works as a video journalist with 麻豆传媒, is currently taking Diclectin during her second pregnancy. Her doctor recommended the medication, and Charles said she trusts that medical professionals have 鈥渄one their homework鈥� when they prescribe the drug.
Charles said she was 鈥渧ery sick鈥� with nausea and fatigue, but saw an improvement in her symptoms after a week or two of taking Diclectin.
鈥淚 don鈥檛 think it is a magic pill 鈥� but for me it really has helped,鈥� she said.
With files from 麻豆传媒鈥� medical affairs specialist Avis Favaro and producer Elizabeth St. Philip
