Acne drug safety study was delayed by B.C. government
Active ingredient has caused birth defects, prompted abortions
A safety study of a powerful acne drug, which has caused hundreds of fetuses to be aborted in Canada and other babies to be born with devastating birth defects, was delayed by more than a year because the B.C. government refused to provide key data.
The research, released Monday in the Canadian Medical Association Journal, outlined the serious health effects for women who get pregnant while taking the acne drug Accutane.
But the authors had to put their work on hold for more than a year as they tried to convince the B.C. government to give them access to public health data that the province had locked down after its botched 2012 firing of eight ministry health researchers.
“It probably delayed the study by about a year,” said lead author Dr. David Henry, a senior scientist with the Institute for Clinical Evaluative Sciences in Toronto.
“We put the study on hold. We obviously wanted to complete the study because we thought there was a safety issue. We suspected from the results from the other provinces that the pregnancy prevention program wasn’t really being adhered to the way it should be.”
The government has admitted it overreacted in firing the eight health researchers in 2012, based on a flawed internal review into allegations of contract mismanagement and data handling. But the province also froze, suspended or otherwise interrupted access to data for other provincial and national health researchers as it grappled with its internal mistakes.
Isotretinoin, the active ingredient in Accutane and its generic cousins, is one of the most toxic drugs to a developing embryo known to medicine. Fetuses exposed to isotretinoin in the first weeks of pregnancy can be born with elongated or conical skulls, wide-set eyes, low-set ears, disfiguring cleft palates or life-threatening heart problems.
But the new study involving nearly 60,000 women prescribed the drug in four provinces — British Columbia, Saskatchewan, Manitoba and Ontario — showed a pregnancy-avoidance program is having only a modest effect in reducing fetal exposure to Accutane.
Over the 15-year study period, 1,473 pregnancies were recorded. Of these, 1,041 ended in medically induced abortions and 290 “spontaneous losses,” or miscarriages.
Of the 118 live births, there were 11 cases (9.3 per cent) of congenital malformations, the team reports in the Canadian Medical Association Journal.
“Poor adherence with the Canadian pregnancy prevention guidelines means that Canada, inadvertently, is using pregnancy termination rather than pregnancy prevention to manage fetal risk from isotretinoin,” said Henry.
Overall, the researchers estimate for every 1,000 women in Canada prescribed isotretinoin, between four and six will conceive while taking a three-month course of the drug. (In Europe, the pregnancy rates are as low as 0.2 per 1,000 female isotretinoin users.)
Women are supposed to have two negative pregnancy tests before starting isotretinoin, sign a consent form acknowledging they have been warned of the risk of birth defects and use two forms of birth control one month before, during and one month after treatment.
However, less than a third of all female users received a prescription for a birth control pill while taking the drug, the study found.
Accutane was approved in 1983 as a last-resort drug for scarring, cystic acne that does not respond to less potent treatments. But its use has increased rapidly with the marketing of generic versions and more doctors are prescribing it for milder cases.
It was unacceptable for the B.C. government to hold up an important national study because of its own internal failings, said NDP critic Adrian Dix.
“The Ministry of Health knew what the study was about, they knew the significance of it, especially for young women in British Columbia,” said Dix.
“It’s a serious mistake and it’s one of the consequences of government’s incompetence on the health firings issue.”
Health Minister Terry Lake said the delays were necessary because B.C. was working with the privacy commissioner to address allegations that the fired researchers had mishandled confidential public health data.
“The reality is we did what we needed to do to protect confidential medical information,” he told the legislature on Monday.
The average age of isotretinoin users in Canada is 24; half of all prescriptions are written for female patients.
According to market research company IMS Brogan, more than 266,000 prescriptions for isotretinoin were handed out last year, up from just over 209,000 in 2011.
The new study, funded by Health Canada, looked at all girls and women aged 12 to 48 in the four provinces for whom one or more prescriptions for isotretinoin were filled in 1996-2011.
The researchers studied only pregnancies that occurred during treatment, “or that could be reasonably assumed to have had exposure,” they write in the CMAJ.
Based on their findings, they estimate one or two children are born with congenital anomalies every year in Canada after being exposed to isotretinoin in the womb.
The study has several important cautions, including that, of the 11 babies with birth defects, the researchers don’t know whether isotretinoin was the cause. They also may have underestimated how many women were taking birth control.
Some may have been using condoms or IUDs.
Nevertheless, Henry says doctors and women need constantly to be reminded of the risks.
In the U.S., doctors and women must register with a mandatory program called iPLEDGE before they can prescribe or use the drug.
The Ministry of Health knew what the study was about, they knew the significance of it, especially for young women.