Last year I attended both Food and Drug Administration
(FDA) hearings on children’s depression
and anti-depressants. Despite my twenty-six years
of clinical practice in behavioral-developmental pediatrics,
I was unprepared for the impact these meetings
had on me. Listening to the testimony of families whose
children have committed suicide while taking one of the
new antidepressants—the selective serotonin reuptake inhibitors—
left the doctors at the hearing shaking their
heads, and watching the intricate dance of government,
academia, and industry confirmed my worst fears about
the relationship between doctors and the drug industry.
The meetings were the culmination of a decade-long
pursuit of justice. In the 1994 case of Wesbecker v. Eli
Lilly, the family of a man who went berserk, killed several
people, and eventually killed himself shortly after starting
to take Prozac claimed that Eli Lilly, which manufactures
Prozac, knew of its potential side effects and had
withheld that information from the public. But when a
parade of industry-financed expert witnesses affirmed the
safety of the drug, a jury voted nine to three to acquit Eli
Lilly. The verdict essentially closed the door to successful
legal challenges to Prozac for nearly ten years.
Several trial lawyers, convinced of the potential agitating
effects of the SSRIs
Paxil, Celexa, Lexipro, and Effexor), continued to
pursue the issue, however. They were joined in the mid-
1990s by a British research psychiatrist, David Healy,
whose analysis of studies funded by the drug companies
demonstrated a consistent signal of increased suicidality—
that is, suicidal thinking and behavior. Their persistent
efforts were rewarded when, under the Freedom of
Information Act, they discovered eight previously undisclosed
studies on the SSRIs and childhood depression.
The new studies had all been filed with the FDA
under the Best Pharmaceuticals for Children Act of 2002,
which reflected a congressional effort to motivate drug
companies to study the effects of medications on children.
The effort is important because children’s metabolism
is different and drugs might affect them differently;
but since children present a smaller market for new drugs,
the pharmaceutical industry might not study them without
some prodding. The act rewards the companies that
perform pediatric studies by permitting them an extra six
months of patent protection, which for a drug like Zoloft
represents an additional billion dollars in sales.
However, the law did not require either the companies
or the FDA to publicize or publish the findings. In the
case of the SSRIs, there were seven existing published
studies, of which only three showed that the SSRIs had
any benefits over placebo in the treatment of pediatric
depression. Healy and company found that all of the
eight unpublished studies were negative. When combined
with the available public data, the overall numbers clearly
showed a lack of effectiveness for the SSRIs and a small
but significant increase in rates of suicidality.
These results were first presented to the United Kingdom’s
FDA equivalent, the Medicines and Health Care
Regulatory Agency (MHRA). In August of 2003, the
MHRA banned the use of most SSRIs for the treatment
of childhood depression. The lone exception was Prozac,
which had been the subject of the three positive studies.
In contrast, there was evidence of much foot-dragging
at the FDA, which operates in a very different “drug culture.”
In America, beginning in the early 1990s with
stimulant drugs like Ritalin, the pediatric use of all types
of psychiatric drugs has skyrocketed. For both ideological
and economic reasons, the practices of American child
psychiatrists changed dramatically over the decade, so
that by 2002 nine out of ten children treated by a child
psychiatrist were taking one or more psychiatric drugs. In
comparison, European child psychiatrists, pediatricians,
and family practitioners (who have an important role in
child health care in the United Kingdom) are far more
parsimonious than their American colleagues with the pediatric
use of psychiatric medications.
It was not then until February 2004 that the first FDA
meeting convened. By that time, a mid-level FDA official
had analyzed the combined data and reached the same
conclusion as the British, but his testimony was withheld
on the procedural grounds that the first meeting’s official
purpose was only to set up the guidelines for reanalyzing
both the public and heretofore secret data. Nonetheless,
the public learned of the eight unpublished studies at the
February meeting. Drug company representatives meekly
explained that they were under no legal basis to publicize the
negative studies, which would have been contrary to the fiduciary
interests of their stockholders. Similarly, there was no
legal obligation for the FDA to publicize the studies. The
FDA simply kept them “on file” to meet the requirements of
the Best Pharmaceuticals for Children Act.
The discovery caused astonishment, dismay, and anger
among those attending the hearing, including doctors, press,
and families of suicide victims who had been taking the medications.
Here was a case where the market system, under the
current regulatory guidelines, clearly failed. Profits trumped
children’s health.
At the second FDA meeting, held in September 2004, the
emotions overflowed. “The
blood of my child’s death is on
your hands,” seethed a mother to
the FDA psychiatrists sitting on
the expert advisory panel. Heeding
the pleas of organized American
psychiatry, however, the
panel stopped short of recommending
an outright ban of
SSRIs’ use for pediatric depression,
but they recommended
that the strongest warning, a
“black box,” be added to the labels
of all SSRIs. As the panel
certainly knew, requiring a black
box warning would also mean
that a warning would have to be
added to any advertisement,
which would effectively end direct-
to-consumer advertising for
the drugs on television and in
magazines.
The meetings have had a profound impact on me. My experience
with the drug companies, beginning with the
marketing of Adderall in the mid-1990s for the treatment of
attention deficit hyperactivity disorder, had already made me
skeptical about their claims and cynical about their growing
connections with medical researchers and organized medicine.
Academic medicine, it seemed to me, was being corrupted by
its ballooning dependency on drug company funding. As a
front-line physician having to make daily decisions about
whom to medicate, I find I have lost faith in my academic colleagues
to give me unbiased advice.
But now my cynicism about the pharmaceutical industry
and skepticism about the advice I get from academic medicine
are also shared by the general public. I daily experience this
growing public mistrust. Ever more parents question “the
data” I present, ask more about long-term adverse effects (my
answer most of the time is “No one knows”), and think much
more about non-pharmaceutical alternatives.
To be sure, not all of this uncertainty is bad, and much of
it is long overdue. The public had been misled by the print ads
and commercials showing the smiling faces of “successful”
children taking the medication. But public mistrust of the
drug companies will inevitably extend to physicians themselves.
And why shouldn’t it, in light of drug industry funding
for national physicians’ conferences and their product
“bazaars,” the continual onslaught of drug detail men with insidious
offers of “free” samples of high-priced, brand-name
medications, and offers of free dinners with five hundred dollar
“consultant” fees that make me feel like a prostitute. American
medicine risks returning, ironically, to the era of “patent
medicine,” when hucksterism and medical practice were synonymous.
Unless clear boundaries (legal
and economic) are drawn between
profit-driven companies
and people’s health, doctors will
lose their aura of scientific objectivity,
so hard-won in the first
half of the twentieth century.
First, medicine’s financial links
to the pharmaceutical industry
must be limited. The funding of
medical education must come
from elsewhere, either from the
government or out of doctors’
own pockets. Industry support
of national professional organizations
must end. The practice
of drumming up business with
free samples must end. And new
regulations must be enacted
that, while allowing for some industry
support of research, absolutely
protect and guarantee
scientific interests. New rules for
a central public registry of all clinical trials, from inception to
completion, have been proposed by drug companies and medical
journal editors, but they may be surpassed by more stringent
regulations from Congress. I have wondered whether
something along the lines of “blind” trusts for medical research
could work, if the drug industry was willing.
Finally, direct-to-consumer advertising should be curtailed.
The drug industry’s claims that DTC advertising serves the
goal of patient education ring as hypocritical as those about
doctors’ CME. The United States is only one of two countries
in the industrialized world to permit this practice.
These reforms are not likely to be enacted. But after listening
to the parents’ cries at the FDA hearings, then coming
home to find that patients’ skepticism has filtered down to the
daily encounters in my office, I am certain that if we don’t
mend our ways as a profession, we will dishonor ourselves as
doctors and rightfully lose the public’s trust.
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