Deadly Medicine:
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' toll.

"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.

UNAVAILABLE

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 public library.

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 it regulates.

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 at N.I.H.

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 career:

"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 twentieth century.

 

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 "scientific medicine"?

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" results public.

"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 the room.

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 pharmaceutical industry.

--RWM (3/11/97)



Ralph W. Moss, Ph.D. is director of the The Moss Reports for cancer patients. Dr. Moss is the author of eleven books and three documentaries on cancer-related topics. He is or has been an advisor on alternative cancer treatments to the National Institutes of Health, the National Cancer Institute, the American Urological Association, Columbia University, the University of Texas, the Susan G. Komen Foundation and the German Society of Oncology. He wrote the first article on alternative medicine for the Encyclopedia Britannica yearbook. He is listed in Marquis Who's Who in America, Who's Who in the World, Who's Who in the East, and Who's Who in Entertainment (as a film documentarian). This Web site does not advocate any particular treatment for cancer. We urge you to always seek competent medical advice for all health problems, especially cancer. Before consulting our site please read our full Disclaimer statement.



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