Flaw in the System: Page Two
When Dr. Joseph Sadusk
said Parke-Davis’s efforts had been “minimal” he selected the right word.
I know this from firsthand experience. A few years ago Mr. Williams changed
his mind about Parke-Davis staying apart from our Foundation and graciously
arranged for three members of the research staff to meet with us on the
subject of Parke-Davis’s Dilantin package insert. (This package insert
is discussed below.)
At this meeting, I
met the senior research officer of Parke-Davis. When we finished our discussion
he mentioned that the FDA had not approved Parke-Davis’s application for
the use of PHT in cardiac arrhythmias. The reason, he said, was that the
company did not supply cardiograms requested by an individual in the FDA.
The research officer said, “We could get them for $100,000 but why spend
the money, all the cardiologists are using PHT anyway.” I won’t take sides
in this hassle between the FDA and Parke-Davis. There was foolishness
to spare. (PHT is so widely used for cardiac arrhythmias that AMA Drug
Evaluations has it in the category of antiarrhythmic agents.) But you’d
think Parke-Davis would have considered it a privilege to spend the $100,000.
A few weeks after
this, a physician applied to our Foundation for a modest grant ($6,000).
He had done interesting preliminary work on the use of PHT as a protection
against brain damage after cardiac arrest. We intended to make the grant,
but it occurred to me that the new Parke-Davis management might appreciate
the opportunity. I called my new acquaintance, the research officer, and
asked him about it. It didn’t surprise me that I was told no. It did surprise
me how quickly I got the answer, on the phone, without consideration of
the matter. The senior officer explained that Parke-Davis was spending
its research moneys on a new medicine the company hoped to patent. I thought
there will be snow on the Devil’s roof before they came up with as good
a medicine as Dilantin. But I got the point—patents on Dilantin had expired.
Well, to sum up, Parke-Davis
got Dilantin by luck. They didn’t understand their own product, have done
little to try to understand it, and haven’t spent a bean in furthering
its understanding. This has contributed to the overlooking of PHT.
But let’s see Parke-Davis
in perspective. There’s no Mr. Parke, no Mr. Davis—just an entity with
those names. Since Parke-Davis did not get PHT by the sweat of its research
there was none of the interest in the drug that would be found in a company
that had developed its own product. As a result, new uses for PHT was
a job never assigned to anyone and no one took it upon himself. It has
been easy to cuss Parke-Davis, the entity, but not the people. In fact
I’ve never met anyone at the company I didn’t like.
Dilantin package insert.
I was weaned on the
Securities Exchange Commission. The SEC is a fiend for full disclosure—the
positive as well as the negative. If Parke-Davis operated under SEC regulations
the SEC would have the company in court for the rest of the century because
of the great amount of positive data that’s not disclosed in its package
insert. But Parke-Davis operates under FDA regulations. Apparently full
disclosure is required on the negative side, but no disclosure is permitted
when the evidence is positive, unless it has an FDA listed indication-of-use.
No matter how flimsy the evidence for the negative, it must be disclosed.
No matter how solid the positive evidence, it may not be mentioned. It
seems a poor way to run a railroad.
An example of inexplicable
illogic. For some years prior to 1972, Parke-Davis’s package insert made
reference to a number of the uses of PHT other than epilepsy. In 1971
the insert stated: “Dilantin is also useful in the treatment of conditions
such as chorea and Parkinson’s syndrome and is employed in the treatment
of migraine, trigeminal neuralgia and certain psychoses.” In 1972 reference
to these uses was deleted, although the evidence for their use had been
substantially increased. Unfathomable. I don’t know whether this was the
fault of Parke-Davis or the FDA. But an innocent public has suffered.
I had taken PHT for
about a year when I started talking to doctors about it. These were informal
talks and occurred when chance brought me together with physicians, as
at a dinner or in a locker room. I must have spoken to more than twenty
doctors during that early period. None of them had heard of PHT being
used for anything other than epilepsy. The discussions were friendly,
but it was almost impossible to get a physician interested in the subject
of PHT. I thought this was because, as a Wall Street man, I was an improbable
source of medical fact.
But my lack of credentials
was the smallest part of the communication problem. In the physicians’
minds there was the fixed notion that PHT was just an anticonvulsant.
They had been taught this in school, the “knowledge” had been in their
heads for a long time, and had calcified. Don’t pick on the physician.
Calcification of ideas is a human trait not special to him.
There was an even
bigger obstacle—the sure knowledge the physician had that if Dilantin
had as many uses as I said it had, they would have heard about them from
Parke-Davis. After all, Dilantin was their product, wasn’t it? And they
wanted to make money, didn’t they? This “irrefutable logic” always defeated
me. If I tried to explain, time would run out before we could get back
There’s been a recent
trend to knock the doctor. I think it’s a reaction to the pedestal position
we had him in a decade ago. We learned from “Dr. Kildare” and “Marcus
Welby, M.D.” that there are two physicians to every patient. In real life
this isn’t so. Doctors rarely make house calls anymore. They can see three
patients in the office for one in the home—and still it’s hard to get
an appointment. Don’t blame the doctor. It’s the ecologists’ fault—they’ve
allowed the spread of Homo sapiens to get out of hand.
When you are giving
a member of the medical profession a hard time (in your head of course—who
would dare do it in person), consider that the doctor’s day never ends.
Sick people don’t care what time it is, and the doctor has to go around
with a beeper attached to him or be in constant touch with his telephone
service. This means twenty-four hours’ tension. We complain about what
the doctor doesn’t do. But do we appreciate the things he does that we
We come to an important
subject: medical literature. Medical studies are called literature (Shakespeare
might demur) when they’re published in a medical journal or as part of
the record of a medical conference. There is a great deal of this literature.
You could wallpaper the world with it and have enough left over to do
your kitchen. The notion that physicians know what’s contained in the
literature is bizarre. But some of them sound like they half believe they
do. If you ask a physician a question he can’t answer, don’t be surprised
if he responds, “Nobody knows.” Which seems to suggest he has read all
the literature and has total recall.
It’s estimated that
there are 3,300 medical journals in the world. A poll in seventeen counties
of upstate New York (not exactly the boondocks) showed that the average
physician subscribed to 4.1 of these journals. Double this figure if you
like. Even if he or she reads the 8.2 journals cover to cover, he or she
would still be 3,291.8 journals short. You can see it’s impossible to
expect the physician to read the medical literature to determine which
drugs he or she should use. That’s why, in this day of specialization,
this is left to the drug companies and the FDA.
However, when a physician
gets a new idea about an approved drug, he or she may apply it. (Former
FDA Commissioner Charles C. Edwards states: “Once the new drug is in a
local pharmacy, the physician may, as part of the practice of medicine…vary
the conditions of use from those approved in the package insert, without
obtaining approval of the FDA.” The Federal Register, Vol. 37,
No. 158, Aug. 15, 1972. This was clearly restated in the April, 1982,
FDA Drug Bulletin.) But the opportunity doesn’t come up often.
Usually new uses of a drug are well explored by the drug company that
introduced it. PHT has been a marked exception, and a rare opportunity
was presented to the physicians.
The medical profession
did not fail us. The work of thousands of physicians has given us a rich
literature on PHT. This literature, international in scope, covers a wide
variety of medical disciplines. Published in many languages over a period
of years, it is spread far and wide. But intermingled with millions of
other studies, this literature is almost lost unless someone seeks it
The science fiction
writer Robert Heinlein calls it the Crisis of the Librarian: “The greatest
crisis facing us is not Russia, not the Atom Bomb...It is a crisis in
the organization and accessibility of human knowledge. We own an enormous
‘encyclopedia’ which isn’t even arranged alphabetically. Our ‘file cards’
are spilled on the floor, nor were they ever in order. The answers we
want may be buried somewhere in the heap....”
Let me give you an
example of how difficult it would be, even in a single field, for a physician
to be acquainted with the literature on PHT. Disorders in the field have
many names. A general description of the field is uncontrolled muscle
movement, or continuous muscle fiber activity. To illustrate the point,
we made up a table of twenty-one published studies on this subject in
1975. (Since then many more studies have been published. See The
Broad Range of Clinical Use of PHT.) These studies show dramatic
recovery in intractable patients when given PHT. In many of the cases
myogram readings (electrical muscle recordings) confirmed the clinical
observations. The difficulty an individual physician would have in becoming
acquainted with this work is shown by the following:
The studies were published
in eight different countries, in sixteen different journals—Journal
of Neurology, Neurosurgery and Psychiatry, Lancet, The
Practitioner, South African Medical Journal, Klinische Wochenschrift,
Arquivos de Neuro-Psiquiatria, Acta Neurologica, Proceedings
of the Australian Association of Neurologists, Ceskolovenska Neurologie,
Connecticut Medicine, Neurology, Archives of Neurology,
New York State Journal of Medicine, California Medicine,
and New England Journal of Medicine.
In only two of the
twenty-one studies was the word phenytoin used in the title. The other
studies were published under such dissimilar titles that Scotland Yard
couldn’t have found them, without the key word phenytoin. Some members
of the medical profession have prescribed PHT for a variety of purposes
for many years. The breadth of its use has been more than might be imagined.
IMS America Ltd. surveys the use of thousands of drugs. For their estimate
of the many clinical conditions for which physicians are using PHT, see
The Broad Range of Clinical Use
One might draw the
conclusion from the IMS America survey that the medical profession knows
all about PHT. But this is not the case. Many physicians know of one or
several uses of PHT. Few have an overall picture of the drug. Thus we
have a strange situation. Dr. Jones prescribes PHT for depression. Dr.
Smith uses it for migraine. Dr. Hemplewaith for trigeminal neuralgia.
But, if a patient asks Dr. Snodgrass if he could try PHT for any of these
purposes, he may get ushered from the office with the admonishment that
PHT is only for epilepsy.
The right of a physician
to prescribe whatever drug he wants is fundamental. But in making his
decision he should have a reasonable amount of evidence on which to base
his judgment. A reasonable amount of information has not been available
to the physician, at least not from the expected source, the drug company.
The informsation has been there, but it’s been hidden in millions of medical
papers, like trees in a forest.
When physicians know
more about PHT they will realize they have been imposed on by the system
and deprived of a remarkable therapeutic tool.
Page: A Flaw in the System Page 3