Sign the petition calling on Hoffmann-La Roche to tell the truth about the side effects of Accutane (Roaccutane) here.

Link to my book The Goose That Laid the Golden Egg: Accutane, the truth that had to be told here.

When Accutane came out on the American market, after being rushed through the FDA approval process, it was listed as a category C drug for risk of birth defects, meaning that it was only of moderate risk. The PDR said that women “should not” get pregnant while on Accutane. Moderate risk means that there are some studies in animals showing birth defects, but it isn’t clear that it is really relevant to humans. There was no requirement that doctors test for pregnancy, or that women take birth control.

Accutane hit the media and was hailed as a wonder drug. Sales soared far being the wildest expectations of Roche executives. Soon every girl with pimples was demanding that pill that her school-mate got that had made her blemishes vanish away.

But not everyone was so sanguine. The Europeans weren’t impressed by Accutane. It was banned in Sweden and Italy and sharply curtailed in other countries, probably related to the results of those trials, which might have included birth defects associated with the use of Accutane.

If there were any birth defects in the European trials, were they reported to the FDA?

Nobody seems to remember. Hmm…

In a series of articles over a decade ago in a newspaper called the Columbus (Ohio) Dispatch, Mark Somerson reported on this story in a series of investigative journalism articles. Remarkably this story about a drug that was equally dangerous as thalidomide never made it beyond the shores of the Wabash River.

Thanks New York Times!

Here’s a scoop for you guys, Mike and Juliet, to add to your ongoing Accutane “investigations”!

It wasn’t only the Europeans that were wary of Accutane, some American dermatologists were as well. In fact, Frank W Yoder, MD, who with Gary L. Peck MD was the first to report on the use of isotretinoin for the treatment of acne in 1977, long before Roche picked it up, warned against the dangers of the drug in the January 1983 edition of the Journal of the American Medical Association, saying that “the potential toxicity of this drug has been seriously underemphasized”. Both American doctors and scientists working for Roche later testified that is was known before it came out on the market that Accutane potentially had a very dangerous risk of birth defects, based on the fact that it was derived from Vitamin A related compounds, well known for many years to cause birth defects in women. Yoder and another doctor involved in the US trials remembered discussing birth defects that occurred during the European trials, although exact names of individuals involved were never produced.

In fact, Roche had known about Accutane for years before the American dermatologists had written about it, but did nothing with the drug. Somerson reported that Dr Werner Bollage, a scientist with the company, wrote in 1971 that it was “inconceivable to develop an agent” that caused birth defects for such a “common complaint as acne.”

For their US clinical trial in the early 1980s, Roche required that all women get tested for pregnancy, and one woman who got pregnant was advised to get an abortion. However, once the drug went on the market, this was no longer required, according to reporting by Somerson.

Henry H. Roenigk MD, another dermatologist who had been involved in the US Accutane trial, was quoted as saying that he published a letter in the May 1982 edition of the journal Dermatology warning of the risk of birth defects, and stating that there had already been birth defects with Accutane (presumably in Europe). Following this Roche wrote a letter to all doctors who had been involved in the US trial and told them not to “divulge trade secrets.”

Nine months after Accutane went on the market in May 1982, babies with birth defects started to appear.

In Sept 8 1983, after the first US birth defect cases were reported, Health Research Group wrote to the FDA urging them to require pregnancy tests and not to bury the warnings about birth defects in the “fine print” at the end of the product labeling.

By 1988 the FDA estimated there could be as many as 1,300 babies born with birth defects because of Accutane. Some of the babies were so deformed that they died in pain after only a few years of life in an institution. Probably many times more babies had mild cognitive defects. And what is worse, despite all efforts, rates of birth defects never went down until iPLEDGE.

Noone deserves that, for any reason.

Originally posted September 28, 2008

My book The Goose That Laid the Golden Egg: Accutane, the truth that had to be told, has been released with 39/42 five star reviews on Amazon and available in paperback or $0.99 on Kindle here. See here for all outlets where it can be obtained.

Part 1

Part 2

Part 3

Part 4

Part 5

This announcement caused an outpouring of vitriol (e.g. calling my study “faked” and “junk science”), first from lawyers working on behalf of pharma and device makers, writing in the Drug and Device Law blog, then from an MD who works as writer and marketer for pharma and pharma-sponsored CME. I felt I need to set the record straight on a number of points that were made.

First of all, it is not true that the study was “commissioned for the litigation”. Eighty percent of the study was paid for by money donated by Liam Grant of Ireland. Brain scans aren’t free. Roche refused to do a study. In fact, back in 1999, I met personally with John McLane, who unbenownst to me was a senior executive for Roche at the time, who refused to even provide medication for the study. I am not an expert in Liam Grant’s litigation (in Ireland you cannot get more than $50,000 in litigation, so he is hardly doing it for the money). I agreed to be an expert after the study was done, not before. Half of all research is supported by pharma. They “commission” research to serve their marketing goals all the time. The bias that introduces has been well documented. When a study is done that is not controlled by them, they go bananas.

Some of the missing data referred to as “bmax” was actually an erroneous term introduced in the course of the 15 depositions (8 hours each) I went through with Roche over this study. The inability to retrieve the numbers was temporary due to problems accessing old media (not an uncommon problem in imaging research). By the time the data was retrieved a court deadline had passed. But it is inaccurate to imply that they were never retrieved.

The reference to not following the study methodology refers to a questionnaire about satisfaction with skin condition (called the Skindex) that was not part of the original protocol, and that was added late, and was not the primary focus of the study.  The original article stated that it was given before and after treatment, but the after treatment results were not presented. As I wrote in a correction later the questionnaire was not given to all of the subjects after treatment.

Roche spent a lot of time and effort trying to debunk this study, in the course of which some data entry errors were found. A re-analysis of the study with corrected data continued to show a reduction in function of the orbitofrontal brain function, in fact the results were more statistically significant than before. Roche next accused me of fraud and asked the journal to retract the paper, which led to an inquiry at my university where the committee had access to all the data and legal documents, and cleared me of the charges of fraud, recommending a letter of correction based on the corrected data, which led to this single sentence correction published in the journal.

The conclusion that Accutane can cause depression shouldn’t rest on a single study, which it doesn’t, as the evidence that retinoids play a role in affective disorders continues to grow.