Day 21
You should spend about 20 minutes on Questions 27-40, which are based on Reading
Passage 3 below.
Examining the placebo effect
BY STEVE SILBERMAN
The fact that taking a fake drug can powerfully improve some people’s health - the
so-called placebo effect
-
was long considered an embarrassment to the serious practice
o f pharmacology, but now things have changed.
Several years ago, Merck, a global
pharmaceutical company, was
falling behind its rivals in sales. To
make matters worse, patents on five
blockbuster drugs were about to
expire, which would allow cheaper
generic products to flood the market.
In interviews with the press, Edward
Scolnick, Merck’s Research Director,
presented his plan to restore the firm to
pre-eminence. Key to his strategy was
expanding the com pany’s reach into the
anti-depressant market, where Merck
had trailed behind,
while competitors like
Pfizer and GlaxoSmithKline had created
some of the best-selling drugs in the
world. “To remain dominant in the future,”
he told one media company, “we need to
dominate the central nervous system.”
His plan hinged on the success of an
experimental anti-depressant codenamed
MK-869. Still in clinical trials, it was a
new kind of medication that exploited
brain chemistry in innovative ways to
promote feelings of well-being. The
drug tested extremely well early on, with
minimal side effects. Behind the scenes,
however, MK-869 was starting to unravel.
True, many test subjects treated with the
medication felt their hopelessness and
anxiety lift. But so did nearly the same
number who
took a placebo, a look-alike
pill made of milk sugar or another inert
substance given to groups of volunteers
in subsequent clinical trials to gauge
the effectiveness of the real drug by
comparison Ultimately, Merck’s venture
into the anti-depressant market failed.
In the jargon of the industry, the trials
crossed the “futility boundary” .
MK-869 has not been the only
much-awaited medical breakthrough
to be undone in recent years by the
placebo effect. And it’s not only trials of
new drugs that are crossing the futility
boundary. Some products that have been
on the market for decades are faltering in
more recent follow-up tests. It’s not that
the old
medications are getting weaker,
drug developers say. It’s as if the placebo
effect is som ehow getting stronger.
The fact that an increasing number of
medications are unable to beat sugar
pills has thrown the industry into crisis.
The stakes could hardly be higher. To win
FDA approval, a new medication must
beat placebo in at least two authenticated
trials. In today’s economy, the fate of a
well-established company can hang on
the outcome of a handful of tests.
Reading Passage 3
W hy are fake pills suddenly
overwhelming promising new drugs
and established medicines alike? The
reasons are only just beginning to be
understood. A network of independent
researchers is doggedly uncovering the
inner workings and potential applications
of the placebo effect.
A psychiatrist, William Potter,
who knew
that some patients really do seem to get
healthier for reasons that have more to
do with a doctor’s empathy than with the
contents of a pill, was baffled by the fact
that drugs he had been prescribing for
years seemed to be struggling to prove
their effectiveness. Thinking that a crucial
factor may have been overlooked, Potter
combed through his com pany’s database
of published and unpublished trials
including those that had been kept secret
because of high placebo response.
His team aggregated the findings from
decades of anti-depressant trials, looking
for patterns and trying to see what was
changing over time.
W hat they found
challenged some of the industry’s basic
assumptions about its drug-vetting
process.
Assumption number one was that if a trial
were managed correctly, a medication
would perform as well or badly in a
Phoenix hospital as in a Bangalore
clinic. Potter discovered, however,
that geographic location alone could
determine the outcome. By the late
1990s, for example, the anti-anxiety drug
Diazepam was still beating placebo in
France and Belgium But when the drug
was tested in the U.S., it was likely to
fail. Conversely,
a similar drug, Prozac,
performed better in America than it did in
Western Europe and South Africa. It was
an unsettling prospect: FDA approval
could hinge on where the company
chose to conduct a trial.
Mistaken assumption number two was
that the standard tests used to gauge
volunteers’ improvement in trials yielded
consistent results. Potter and his
colleagues discovered that ratings by trial
observers varied significantly from one
testing site to another. It was like finding
out that the judges in a tight race each
had a different idea about the placement
of the finish line.
A fter some coercion by Potter and
others, the National Institute of Health
(NIH) focused on the issue in 2000,
hosting a three-day conference in
Washington,
and this conference
launched a new wave of placebo
research in academ ic laboratories in the
U.S. and Italy that would make significant
progress toward solving the mystery of
w hat was happening in clinical trials.
In one study last year, Harvard Medical
School researcher Ted Kaptchuk
devised a clever strategy for testing his
volunteers’ response to varying levels of
therapeutic ritual. The study focused on
a common but painful medical condition
that costs more than $40 billion a year
worldwide to treat. First, the volunteers
were placed randomly in one of three
groups. One group was simply put on
a waiting list, researchers know that
some patients get better just because
they sign up for a trial. Another group
received
placebo treatment from a
clinician who declined to engage in small
talk. Volunteers in the third group got the
same fake treatment from a clinician who
asked them questions about symptoms,
outlined the causes of the illness, and
displayed optimism about their condition.
Not surprisingly, the health of those in the
third group improved most. In fact, just
by participating in the trial, volunteers in
this high-interaction group got as much
Day 21
relief as did people taking the two leading
prescription drugs for the condition.
And the benefits of their “bogus”
treatment persisted for weeks afterward,
contrary to the belief-widespread in the
pharmaceutical industry that the placebo
response is short-lived.
Studies like this open the door to hybrid
treatment strategies that exploit the
placebo effect to
make real drugs safer
and more effective. As Potter says, “To
really do the best for your patients, you
w ant the best placebo response plus the
best drug response.”