[Ip-health] Time online: Why New Drugs Don't Live Up to the Hype - A schizophrenia study shows, once again, that second-generation drugs are not necessarily the big leap forward they are touted to be. And what to do about it

[James Love]

http://www.time.com/time/health/article/0,8599,1112444,00.html?
promoid=3Drss_top

Viewpoint: Why New Drugs Don't Live Up to the Hype
A schizophrenia study shows, once again, that second-generation drugs
are not necessarily the big leap forward they are touted to be. And
what to do about it
By CLAUDIA WALLIS
Posted Friday, Sep. 30, 2005

When a new generation of drugs for schizophrenia began appearing in
the early 1990s, there was rejoicing=97and relief. Finally, patients
had alternatives to old sledgehammers like Thorazine and Haldol,
notorious for causing bizarre tics like lipsmacking and other jerking
movements that might justify the fear=97so common in schizophrenics=97
that everybody's staring at them. I remember the excitement in my own
family. One of my siblings, now in her 40s, has endured the rattling
demons of this disease since adolescence. About five years ago she
tried the newly marketed Zyprexa (olanzapine). Before long she was
astoundingly better: no paranoia, no voices, but an abundance of
calm, even placid, rationality. Within two years, however, this
always-slender, 110-lb. vegetarian had gained 47 lbs. and a new
affliction: diabetes. Zyprexa was out, and she was moved to Geodon
(ziprasidone), another newfangled antipsychotic, which made her feel
antsy at first but works quite well.

With schizophrenia, you pick your poison. But until last week, it
often felt like a game of chance, played with a loved one's precious
marbles. Now, thanks to a landmark study by the National Institutes
of Health (NIH) comparing four of the new drugs and one older one, we
finally know how these potions stack up. All in all, the results are
pretty heartbreaking. Three-quarters of the nearly 1,500 patients in
the 18-month trial stopped taking the drug they were assigned, often
because it wasn't working or had intolerable side effects. Zyprexa
did best (merely 64% dropped out), but, yup, it carries a high risk
of weight gain and diabetes. Three other second-generation drugs
turned out to be no more effective than the old one, Trilanfon
(perphenazine)=97a cousin of the sledgehammers but with a somewhat
better picture on side effects. As a matter of fact, by one measure,
you're better off with the old drug: it costs about $45 a month,
while the new ones cost $400 to $500 more.

But wait, haven't we heard this story before? Does the phrase 'water
pill' ring a bell? Three years ago another big NIH study showed that
a cheap, old-fashioned diuretic (a.k.a. water pill) worked better for
most folks with high blood pressure than did costly, cutting-edge
medications. (These included a calcium-channel blocker and an ACE
inhibitor). Then there's the sad lesson of Vioxx and its ilk. That
category of painkillers captured a $5 billion-a-year market on the
celebrated promise that they were safer than older, cheaper
analgesics like Tylenol or Advil. In this case, as the nation learned
when Vioxx and Bextra were withdrawn and Celebrex got slapped with a
black-box warning, we were paying a premium to trade a sizable risk
of tummy trouble for a smaller but still troubling risk of heart
attacks and strokes.

Results as disappointing as these raise big questions. The first one
I asked myself with respect to my stepsister is: Why didn't we know
this sooner? Why do we keep putting new drugs on the market, promote
them like crazy, get everybody excited, sell billions of dollars
worth, and then find out that they're not the giant step forward we'd
hoped for? Isn't the Food and Drug Administration obliged to find out
this stuff in the approval process?

The surprising answer is no. Sure, the FDA is supposed to make sure
that new drugs are safe and effective and that promotional claims
about them don't get out of hand, but the agency defines efficacy as
outperforming a sugar pill. 'You do not have to show one drug is
better than another,' explains Dr. Robert Temple, who heads the FDA's
office of medical policy. (The exception: new drugs are tested
against older therapies in devastating ailments like cancer or AIDS,
when it would be unethical to give a control group placebos.) While
Temple plainly sees the value of studies comparing new drugs to old,
it might take an act of Congress, he says, to assign that task to the
FDA: comparative studies, which cost big money, 'are hard to execute
under the current law.'

So whose job is it to compare pills? 'I don't think there's a clear
answer right now,' Temple concedes. 'And with the new Medicare drug
benefit about to soak up large amounts of money, we need to answer
this.'

The vast majority of U.S. drug research is conducted by
pharmaceutical companies, but few experts trust them to do head-to-
head matchups. It's just too easy for a company to tilt the odds in
its own favor by choosing the weakest rival drug or by playing around
with dosages or the patient-selection process.

So it is the NIH that rides to the rescue. The National Institute of
Mental Health (nimh) paid $42.6 million to study existing drugs for
schizophrenia. It's money well spent, says institute director Dr.
Thomas Insel, but 'that's money we can't put into developing the next
generation of these compounds or understanding the biology of this
disease.'

And it means waiting until long after drugs have been approved and
desperate hopes raised to learn what might have been gleaned much
sooner. The FDA has come under increasing criticism for mishandling
the drug-approval process, culminating last week in the resignation
of its chief, Lester Crawford. Maybe it's time for Congress to
redefine that process. 'The FDA should not approve a drug unless it
is shown to be better in some way than the existing drugs,' suggests
Dr. Marcia Angell, former editor of the New England Journal of
Medicine and author of The Truth About the Drug Companies. A better
drug, she notes, could be defined broadly: fewer side effects, easier
to take, longer lasting, more effective in a subset of patients. Such
a policy would not only speed vital information to doctors, it would
also spur drug companies to focus on creating truly novel medications
rather than minor variations on existing themes, what many
researchers call 'me too' drugs. 'The pace of innovation has been
slow,' says Dr. Jeffrey Lieberman, chairman of the psychiatry
department at Columbia University Medical Center and lead author of
the study.

If there's one lesson from last week's drug news, it's this: what we
need=97for those with schizophrenia and so many other ailments=97is
something new and improved that truly lives up to the hype.

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James Love, CPTech / www.cptech.org / mailto:james.love@cptech.org /
tel. +1.202.332.2670 / mobile +1.202.361.3040