Healthy Skepticism Library item: 2007

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Langreth R.
Drug Marketing Drives Many Clinical Trials
The Wall Street Journal 1998 Nov 16

Full text:

Ask drug-industry executives why their new pills cost so much, and it’s a good bet they will cite the high cost of clinical trials.

Certainly, proving to regulators that a new drug safely does what it
is supposed to is an expensive process: Exhaustive drug testing can
cost $150 million or more for a single medication, and only 10% to 20%
of drugs that enter early trials ever make it to market.

But satisfying the Food and Drug Administration isn’t the only reason
that clinical-trial costs have ballooned to about $7 billion annually,
or almost 40% of the industry’s U.S. research budget.

As it turns out, fully one-quarter of the patients in clinical trials
are enrolled in studies that continue beyond the initial approval of a
drug. Why spend millions testing a remedy that has already won the
government’s blessing? Take a look — as many drug-industry executives
have — at what Bristol-Myers Squibb Co. did with its cholesterol drug
Pravachol.

In a calculated bet in 1989, the company poured almost $50 million into
a large and lengthy human trial of the pill. Not to prove whether it
lowered cholesterol, but to show for the first time that taking such a
potent cholesterol remedy could reduce the risk of heart attack among
healthy people with high cholesterol. Winning that distinction would
give Bristol-Myers powerful ammunition against Merck & Co., which had a
head start in the market with its drug Mevacor and was readying a
second anticholesterol pill, Zocor. Bristol-Myers also needed long-term
studies to convince skeptical health-maintenance organizations that
cholesterol drugs really did improve patients’ health.

Marketable Data

Six years and 6,595 test patients later — four years after Pravachol
came to market — the data emerged. There was a 31% reduction in heart
attacks and deaths in the patient group that received Pravachol for
five years, compared with patients who received a placebo. In actual
numbers, the figures were much more modest: For every 1,000 patients,
there were 22 fewer heart attacks or deaths.

Nonetheless, the results were enough to win Bristol-Myers an
unprecedented blessing from the FDA in 1996 to promote Pravachol as
the only cholesterol-lowering agent to protect otherwise healthy
people against heart disease.

Bristol-Myers began advertising Pravachol as a heart-attack prevention
therapy, and sales of the drug soared. It now ranks third among
anticholesterol drugs in the U.S. — a crowded, $6 billion category —
with about 18% of total prescriptions, according to marketing-research
firm IMS Health. (Zocor ranks second with 27%, thanks to the
groundwork laid by Merck’s Mevacor, while Warner-Lambert Co.‘s
Lipitor, a more potent drug, is No. 1 with 39%.)

Now, what looked at first like a multimillion-dollar gambit by
Bristol-Myers has become a model for the industry. Pharmaceutical
companies have greatly expanded their clinical testing, often
measuring their new products against myriad rivals in hopes of finding
incremental differences that will allow them to land a better ad
slogan, a broader treatment claim or a spot on the restricted list of
products insurers will reimburse.

Beyond FDA Requirements

The number of drug trials has exploded far beyond the dictates of the
FDA, which says its requirements haven’t grown substantially in recent
years. FDA regulations require only that drug makers prove their new
entries are safe and effective compared with a placebo or, when that
isn’t appropriate, another drug. But many trials today go well beyond
that. The typical new medication undergoes almost 70 clinical trials,
compared with just 30 trials in the 1970s. As a result, the testing
bill for each new drug submitted to the FDA is rising by about 12% a
year, according to research firm DataEdge LLC, Fort Washington, Pa.
The companies say this is because they are tackling tougher diseases
and performing more safety tests.

But increasingly, marketing executives are joining research teams from
the start, surveying doctors and consumers and tailoring trials to win
optimal “positioning” in the marketplace. Many of the biggest trials
come not in difficult-to-treat diseases such as cancer, as one might
expect, but in well-established therapeutic areas, such as antibiotics
or blood-pressure drugs, where enormous testing programs are needed to
ferret out small advantages over existing drugs that can then be
highlighted in marketing campaigns.

Postmarketing studies, as trials for drugs already on the market are
called, “are billowing out of control,” says Eve Slater, Merck’s
senior vice president for clinical testing. She decries “a total lack
of science” in some studies. But drug marketers contend they are
helpless to stop the one-upmanship. If a rival mounts a new study
aimed at backing up a sales-expanding marketing claim, “you have to do
it, too, or you are dead in the water,” she says.

High Pressure

Bristol-Myers is currently testing a powerful new blood-pressure drug,
omapatrilat, in one of the largest clinical-trial programs it has ever
waged. It will monitor 20,000 to 25,000 patients in dozens of
countries over the better part of a decade. The total cost could hit
$200 million, company officials say.

Omapatrilat is billed as an improvement upon a well-tested class of
hypertension drugs, known as ACE inhibitors, that have been on the
market for almost two decades. Existing ACE inhibitors don’t always
lower blood pressure enough, however, and often they don’t work well
for African-American patients. In the early 1990s, Bristol-Myers
researchers discovered a chemical that, in test tubes, blocked the
same bad hormones as old ACE inhibitors, while also boosting levels of
other “good” hormones that regulate heart function and blood pressure.

To capture a beachhead in this competitive drug category,
Bristol-Myers’s marketers proposed an ambitious plan: test omapatrilat
in a giant clinical trial against the three most heavily marketed
classes of blood-pressure medications (ACE inhibitors such as Merck’s
Vasotec, calcium-channel blockers such as Pfizer Inc.‘s Norvasc, and
angiotension II inhibitors such as Cozaar, also made by Merck).
Scientists heading the omapatrilat clinical-testing team readily
agreed, and large-scale trials began on about 5,000 people last year.

“The FDA told us that we don’t need all these trials” to get
omapatrilat approved for blood pressure, says Hubert Pouleur,
Bristol-Myers’s vice president for cardiovascular clinical research.
“But there is a difference between getting a drug approved and having
it be a commercial success. A new drug will be used only if it is a
significant improvement on existing drugs, and to establish that you
need trials that aren’t required for approval.”

Staking a Claim

The trial strategy, if successful, will allow Bristol-Myers to make
the powerful marketing claim that its drug lowers blood pressure more
than its competitors’ products. The company also is testing its drug
among the elderly as a class and among blacks — trials that could
help in marketing to these patients.

Early next year, researchers will begin an even larger round of
testing on more than 10,000 patients that will span five years and
seek to prove that omapatrilat reduces the incidence of heart attack
and death from cardiovascular disease. These trials need to be
especially large because some existing drugs, in particular ACE
inhibitors, have already been shown to reduce cardiac events, and
Bristol-Myers is looking for an advantage over them. Sol Rajfer,
senior vice president of clinical research and development at
Bristol-Myers, says the clinical onslaught “is driven by science” and
isn’t only about market positioning. “These trials help doctors use
the drugs wisely,” and could result in important public-health
benefits, he says.

Yet Anthony Coles, a doctor who heads cardiovascular marketing at
Bristol-Myers, puts it more bluntly. In a pharmaceutical category as
crowded as hypertension, he says, “you have to show your drug gives a
benefit beyond reducing blood pressure.”