Why Tens of Thousands of Heart Patients Died
in America's Worst Drug Disaster
by Thomas J. Moore
(New York: Simon & Schuster, 1995,
$23.00, ISBN 0-684-80417-4)
A REVIEW ARTICLE
© 1997 by Ralph W. Moss, Ph.D.
This is an extraordinary book. It tells how, in just a few years, approximately
50,000 people died from taking drugs that were intended to prevent cardiac
arrest. The book focuses on two drugs in particular: "Tambocor"
(flecainide acetate), manufactured by 3M Pharmaceuticals, and "Enkaid"
(encainide), from Bristol Laboratories.
Ironically, such class I anti-arrhythmics were given to patients because
their doctors believed that by preventing abnormal heart rhythms they could
prevent sudden heart attacks. Instead, the opposite proved the case--the
drugs themselves represented a greater danger.
"Often the effect was so sudden," says the book's author,
Thomas J. Moore, "that people literally dropped dead while going about
their normal lives."
The death toll from these class I anti-arrthymics will never be known
for certain. But Moore presents absolutely compelling evidence that between
the years 1989 and 1990, between 40,000 and 70,000 lives per year were lost
from the six largest-selling class I drugs. And that was only two years'
"Throughout the decades," says Moore, "it is clear
that hundreds of thousands died prematurely..." (p. 287). What
is more, such drugs continue to be widely prescribed.
Hundreds of thousands of deaths--you heard me right! Even if we choose
the more conservative figure of 50,000 deaths, quoted on the book's cover,
the toll from Tambocor and related compounds is greater than total U.S.
combat losses in Korea or Vietnam, and greater than all the commercial
airplane crashes in U.S. history taken together.
Have you heard about this? Probably not. Public knowledge of this major
disaster has been extremely limited, and the reaction of the medical community,
the media and the government has been muted, at best. In fact, Moore's book
itself has suffered a mysterious fate. It went out of print just one
year after its initial publication in late 1995. The publisher Simon
& Schuster decided, apparently on commercial grounds, not to bring out
a paperback edition, and no other company has so far expressed an interest
in doing so. Today, if you search for it on Amazon.com, the massive Internet
bookseller, you are informed that "THIS ITEM IS CURRENTLY NOT
AVAILABLE. We suggest that you occasionally check this page to see if it's
been reprinted." I was lucky. I managed to find a single copy at a
Yet Thomas J. Moore is an outstanding investigative reporter in the health
field. He is intelligent, careful and meticulous. Currently a senior fellow
at George Washington University's Center for Health Policy Research, Moore
was formerly an award-winning reporter for the Chicago Sun-Times, where
he was the Washington correspondent. He is also a former staff member of
the U.S. Senate Select Committee on Intelligence. What a sad commentary
on the state of journalism in corporate America that a book like this can
practically vanish without a trace.
Since you may never get a chance to read it, I am providing a longer-than-usual
review of this important work.
DRUG APPROVAL PROCESS
"Deadly Medicine" takes us step-by-step through the FDA drug
approval process. This might sound boring, but if you are interested in
medicine, it is an extremely important topic and very well told. What emerges
is a vivid picture of a soul-less and avaricious pharmaceutical industry,
which long ago figured out how it could dance circles around the Food and
Drug Administration (FDA). FDA is supposed to "regulate" the industry.
Instead, Moore shows that it is really the captive of the industry
He does this without emotionalism, without rhetoric, but with a quiet
accumulation of facts. Perhaps this is one reason that his important message
flew over the heads of the people for whom it was intended.
Anyone who doubts that the monopoly drug companies effectively control
the FDA must read this book. When you finish "Deadly Medicine,"
I think you will agree that a system which can produce a "Tambocor"
disaster is drastically in need of reform.
For example, Moore shows how the 3M company intensively cultivated the
FDA officers who were responsible for approving their drug. They routinely
studied these officers' every thought and action. When the FDA put Dr. Sughok
Chun in charge of 3M's Tambocor application, 3M quickly appointed Florence
Wong to be her constant liaison. The two women had similar backgrounds and
interests. "Chun found her pleasant to deal with," writes Moore.
She was "quick to understand what Chun wanted." In fact, Chun
and Wong would talk on the phone almost every day.
But this "friend" in industry kept detailed notes on every
conversation she had with the FDA officer and promptly passed them along
to her higher-ups. "Much as an intelligence service case officer does
each time he contacts one of his agents," says Moore, in a telling
analogy, "Wong prepared reports of the conversations she had with Chun
and other FDA officials."
In the end, we are not surprised that "Chun was enthusiastic about
Tambocor. She thought its main properties were well documented in a clear
and crisp analysis....She recommended that Tambocor be approved for use
for a wide range of heart rhythm disorders....Tambocor had passed its first
hurdle to FDA approval...." (p. 123). We readers look on in horror
as Moore recreates the atmosphere at FDA, in which a disaster of this
proportion can unfold without anyone waving a warning flag.
Of special interest is Moore's description of the activities of
Robert Temple, M.D., Dr. Chun's boss at FDA, who ultimately was responsible
for the approval of Tambocor and the other class I drugs. Temple was
recently appointed an ex officio member of the Alternative Medicine Program
Advisory Council, the body that advises the Office of Alternative Medicine
Temple would be an easy target for Moore to lambast. But I found his
portrait of the FDA official carefully nuanced and generous, considering
the magnitude of the mistakes committed in this case. Moore appreciates
Bob Temple's intelligence and quick attention to details. Moore tells how
Temple graduated from Harvard College and then went on to graduate first
in his class from Columbia University's medical school. As a young doctor,
he volunteered to make speeches before state legislatures against laetrile.
Moore also relates the following illustrative incident from Temple's early
"Bob Temple had barely gotten his feet on the ground at the FDA
when he found himself at a party with the FDA official who recruited him,
Dick Crout, director of the Bureau of Drugs. Crout asked him how he liked
the work. Temple said the work was terrific, but he had a problem. He
didn't have enough work to do. In an organization that was groaning
under an excessive workload, that was all the boss needed to hear. Crout
said he would find plenty for Temple to do. In short order, Temple was
working part-time as Crout's personal assistant...." (p. 105)
Although Temple is described as "a lover of raw data," he is
"not only smart with data," but "quick with words" and
"could use both to achieve the ends he desired." At another point
Moore notes that Temple "under pressure...was capable of fast footwork,
of cutting the fine legal point." (p. 263).
Moore is harder on the so-called "marquee professors," big-name
medical school physicians. These men and women simultaneously serve on FDA
advisory committees that recommend the approval of drugs in their field;
as paid advisors to the pharmaceutical manufacturers of these same drugs;
and as cheerleaders at posh seminars at which the industry convinces doctors
to prescribe these dubious agents.
It's quite a living. Top academic doctors can net hundreds of thousands
of dollars in payments from the drug industry--Moore gives the details.
It's all legal, I guess, and no one really seems to mind, except for a few
vociferous critics, who as this book demonstrates, have little power to
stop the Juggernaut.
But was there a "conspiracy" to approve a deadly medication?
I think one needs to read this book to understand the complexity of it all,
how the many and various parts fit together. For example, conspiracy theorists
will have to account for the fact that Temple himself had grave misgivings
about the safety of this whole class of agents. Yet in the end he bowed
to pressure and approved them.
Everyone may not have been in cahoots, yet they all played their respective
parts and the result was a tragedy of enormous proportions. It is more complicated
by far than eight guys getting together on a boat outside the continental
limits and plotting the end of the world. Yet it was not a tragic oversight,
either. It was simply the way the drug approval system works in the late
APPROVAL BASED ON A THEORY
Moore makes clear that proof of the effectiveness
(much less the safety) of Tambocor has never been adequately established.
Approval was based on a theory that by suppressing premature ventricular
complexes (PVCs) doctors would save their patients from sudden death. There
was no evidence for such a theory. This was the pet idea of some of the
marquee professors--convenient, since drugs existed to stop PVCs. But the
theory turned out to be wrong, tragically wrong. And hundreds of thousands
of people may have lost their lives because of this drug company inspired
theory. It makes one wonder where exactly is the "science" in
What finally exposed Tambocor was an NIH clinical trial called the Cardiac
Arrhthymia Suppression Trial (CAST). This showed that Tambocor and Enkaid
caused dramatically more deaths than did the placebo. The story of how this
test unfolded is extremely detailed and at times may be difficult to follow.
But it is worth whatever effort you put into understanding it. Moore's book
explains, better than any other writings I know, how drug companies manipulate
the whole testing process. One small bright spot is that NIH officials
come off better in this account than you might expect, especially when
viewed in comparison with FDA.
When NIH prepared to announce the disastrous outcome of the CAST study
to the media, the drug companies objected strenuously to making these "premature"
"As if to make the companies' point on another level," says
Moore, "a company lawyer walked down the hallway...and asked to
use the phone to call the White House. A few moments later [Heart and
Lung Institute Director Claude] Lenfant was called out of his office to
take an important call from 'downtown'." The caller was none other
than James Mason, the assistant secretary of health himself. The repercussions
of this phone call were vast, although they remained unseen by the public.
After the CAST results became known, some reformers in Congress tried
to expose what had happened. In a chapter entitled "Temple on Trial,"
Moore shows how ineffective Congress can be in such situations. The main
antagonists in this case were the aforementioned Dr. Temple and Mitchell
Zeller, then counsel to Ted Weiss's (D-NY) Human Resources and Intergovernmental
Relations Subcommittee. Weiss was a liberal reformer from New York City's
West Side who had an interest in the misbehavior of large corporations.
His counsel Zeller worked through 1989 analyzing thousands of pages of
documents and piecing together key episodes in the history of Tambocor.
He then shaped this "mountain of material" into a form suitable
for a congressional hearing. But while Zeller found many cardiologists who
were outraged over the Tambocor tragedy, few of them would testify to this
in public. At least half a dozen turned him down flat. "If they
went public with their criticisms of these drugs," Zeller commented,
"they were concerned that they would lose future funding from the drug
companies." Tom Moore calls this refusal to testify against other
physicians the 11th Commandment of doctors, "Thou Shalt Not Tell."
When the Congressional hearings finally took place there was almost no
public interest. "What was conspicuously absent," says Moore,
"was any specific information about the loss of life, the magnitude
of the error that had occurred." The chief target of the hearings was
Robert Temple, the man who approved Tambocor. Weiss and his fellow
Congressmen zeroed in on him. "There were serious flaws in the evidence
submitted by [3M] to prove that Tambocor was safe for use by persons with
mild or moderate arrhythmias. Isn't that correct?" Weiss demanded.
"Yes," Temple admitted.
But no exact numbers had been established. A few minutes later, Weiss
addressed Temple's FDA colleague, Director of Cardio-Renal Drugs, Raymond
Lipicky. "If you and Dr. Temple had stuck to your guns and not approved
Tambocor for mild or less than life-threatening arrhythmias fewer people
would have died unnecessarily."
But even though Lipicky had once told 3M, "This drug kills people,"
he would not acknowledge that simple fact at a public hearing. "You
don't know how many people died as a consequence of Tambocor," he told
the Congressman. "You have absolutely no knowledge of that and I
don't think that is an established fact. So I don't understand the question."
Everyone involved--drug companies, marquee professors, FDA officials,
outside cardiologists--all united on this one point, that above all other
things, the public must not know the numerical dimensions of the tragedy.
That, after all, was the stuff of headlines, and headlines were to be
avoided at all costs.
And, predictably, after the Congressional hearings, there was not a single
television story, no wire service story, in fact practically no news
coverage at all. When the hearing ended, Temple knew he had won. He
walked over to Mitch Zeller in the nearly empty chamber.
"You still don't get it," he said. Then he smiled and left
Later, in fact, the whole business was used to celebrate the glories
of the drug approval process. Dr. Raymond Woosley, a "marquee"
professor from Vanderbilt University, even told Moore:
"I think the system worked beautifully. Unfortunately some people
had to die, but they were dying anyway, they were dying from other
causes, and there are still people dying from things that are not tested.
There are things going on in the practice of medicine every day that affect
just as many people that are not being studied." (p. 266).
Ironically, Ted Weiss died shortly after these hearings of a sudden heart
attack. After Weiss's death, his counsel Mitch Zeller--the fellow who "still
didn't get it"-- found himself another government job--working
for the FDA.
--Ralph W. Moss, Ph.D.(3/9/97)
PULLOUT BOX: SURROGATE ENDPOINTS
Why would experienced doctors be so eager to "treat" their
patients abnormal test scores (PVCs) instead of finding drugs that have
proven life-prolonging benefits in humans?
The answer, Moore explains, is found in a concept called "surrogate
endpoints." This means that researchers conveniently substitute what may be
an essentially irrelevant test score for an actual symptom.
This is arcane, but important. Moore provides a three-page explanation
of this topic which is very illuminating. If you read his discussion very
carefully, you will come away with a better understanding of why so many
things go wrong in drug approval, and not just in cardiology, either.
Moore explains that back in 1962, reformers like Sen. Estes Kefauver
wanted the refurbished FDA law to require evidence of therapeutic effectiveness
for new drugs. In other words, the companies were supposed to prove
demonstrable health benefits for the patients. But the drug companies and
FDA realized that this would be no simple matter. Few drugs are really demonstrably
effective, and to prove such effectiveness would require them to spend many
millions of dollars. Thus, when the law was finally written, the word therapeutic
was quietly omitted. This simple change opened the door to what Moore
calls "entire families of drugs that provided theoretical benefits
to the patient rather than proven good. These unproven benefits were
called surrogate endpoints. They are effects believed to be surrogates or
substitutes for actual therapeutic benefits" (p. 120).
This is extremely important in helping us understand the lack of effectiveness
of cancer drugs as well.
Moore perceptively writes:
"The surrogate endpoint for anticancer drugs is reduction in tumor
size. Treating a cancer could logically have two objectives--to increase
survival or to improve the quality of remaining life. Cancer drugs are
approved without demonstrating either benefit. Reduction in tumor size
is sufficient. Patients do not necessarily feel better or live longer because
some malignant tumors are slightly reduced in size. As a group, chemotherapeutic
agents are among the most toxic in the entire arsenal of drugs. Because
survival and quality of life studies are not routinely required, there
is no way of knowing which agents do more harm than good." (p. 121).
Once you understand that the FDA approves drugs based on these "surrogate
endpoints" you understand why so many drugs are not really effective
for real human health problems at all. Nevertheless, they are very effective
at improving the bottom line of America's most profitable business, the
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