Acne drug article under fire

Link between author, company is criticized
By ED SILVERMAN
STAR-LEDGER STAFF

A recent journal article on a controversy over Accutane, the acne medicine
blamed for numerous teenage suicides, is causing a controversy of its own.

The November article, which appeared in the Journal of the American Academy
of Dermatology, concluded there's no scientific evidence to link the
best-selling drug to suicide. Dermatologists were, however, cautioned to
watch patients for signs of depression.

But the article, which only reviewed existing literature, was co-authored by
a psychiatrist who is also a consultant to the drug's manufacturer,
Hoffmann-La Roche Inc. And Roche financed publication by providing a grant
to the magazine.


The issue highlights an ongoing debate about the marketing practices used by
the pharmaceutical industry and its ability to influence physicians,
especially when it comes to medicines that generate not only big bucks, but
potentially serious side effects.

"There's a growing body of literature showing the closer the financial tie
to the funder of an article, the more favorable the the findings," said
Arthur Caplan, who heads the Center for Bioethics at the University of
Pennsylvania. "There's always room for interpretation, but when you have a
relationship, you always tend to lean toward the positive."

In this case, the relationship between Roche and the article's lead author,
Douglas Jacobs, a Harvard Medical School psychiatry professor, was
disclosed. So was the grant given to the journal. In response to the
criticism, the author, the journal editor and a Roche spokeswoman denied
that the article or the financial relationships posed a problem. They also
maintained the article was a legitimate way to further discussion of a
complex issue.

One expert in suicide, however, criticized the arrangement because he said
it unfairly obscures the need for more information about links between
Accutane and suicide. In late 1999, a Food and Drug Administration advisory
panel recommended further study. To date, Accutane has been associated with
138 suicides here and aboard, according to regulators.

"My concern is that doctors are going to miss the association between the
author and the drug company," said Peter Gutierrez, a Northern Illinois
University psychology professor and director of the research division of the
American Association of Suicidology.

"It's a perception issue. They know there are questions about the drug and
they're worried about prescription rates," he continued. "If I was a
dermatologist and I was reading this article, I would say they're trying to
cover their butts."

For his part, Jacobs said he reviewed all available medical literature as
well as reports filed with regulators in which depression and suicide were
mentioned among Accutane patients. And he reiterated his belief that there's
nothing to link Accutane to suicide.

"People are free to draw any conclusions they want about my relationship to
Roche, but I was very careful in drawing my conclusions about Accutane,"
said Jacobs, who also runs a nonprofit devoted to mental-health issues. "I
don't see Accutane as a contributing factor in suicide. ... And I don't see
what additional research would accomplish."

Accutane and suicide has always been a confusing topic - both the FDA and
Roche say teenagers with severe acne are likely to be depressed. Roche also
maintains a clear link to suicide doesn't exist, although the Nutley company
last year was required by the FDA to provide informed consent forms to
patients and restrain its advertising.

The issue has plagued Roche since 1998, when a warning was required on the
product label about suicide. Since then, a growing number of lawsuits has
been filed by families who claim the drug hurt their children. Accutane soon
faces generic competition, but the drug is still a big seller, generating
$513 million in sales in first nine months of last year.

Asked about the journal article, a Roche spokeswoman, Carolyn Glynn, said
"funding through educational grants from a pharmaceutical company are a
valid, respected and necessary part of the scientific process."

The journal's editor, Jeffrey Bernhard, said the article was peer-reviewed,
or examined by independent experts, a standard practice. He added that he's
committed to publishing "on subjects of clinical importance to our readers
that examine questions from all angles and contribute to the discussion in
an ongoing way as more information becomes available."

Ronald Wheeland, who heads the American Academy of Dermatology, supported
Bernhard's decision. And he noted that Bernhard runs the journal without
interference from the association, which last year called for further study
of links between Accutane and suicide. But he acknowleged the article posed
a thorny issue.

"This is a very murky area," said Wheeland. "There's this obvious potential
conflict of interest when it comes to a person who represents a company. ...
Could there be a subtle change in the outcome because of his position? I
can't deny it, but I doubt it. If it was so overwhelmingly positive, I'd
have concern. But this was a tempered article."

One attorney, who represents several families, sees it differently.

"It's not unusual for drug companies to hire consultants to publish studies
which tend to diminish the importance of FDA warnings," said David Affinito.
"In this way, drug companies can convey the sublime message to doctors and
their patients that the drugs are safe - in spite of the warnings."


NOTES: Ed Silverman can be reached at esilverman@starledger.com or (973)
392-1542.