Original_To:  BITNET%"mdphd-l@ubvm"
Newsgroups: bit.listserv.mdphd-l
Date:         Tue, 29 Dec 1992 09:35:00 EST
From:         Mike Brooks <BROOKS@UFBIOT.BITNET>
Subject:      interesting essay on the FDA

        The Right Lesson To Learn From Thalidomide

                  Steven B. Harris, M.D.



   The Food and Drug Administration was originally (early in this
century) charged with establishing the purity and safety of foods
and drugs.  As such, it was tolerable, and even did a certain
amount of good in acting as policeman against certain types of
actions which we all agree constitute "fraud" (i.e., putting
horsemeat in the hamburger, putting sugar instead of antibiotic
in the antibiotic pills, etc.)

   But then, and the late 1950's and early 60's, something
horrible happened, both to the citizen and to the State.  In
Europe, a drug called thalidomide was marketed as a tranquilizer.
In America, the FDA official in charge of the American "new drug
application" for thalidomide (Nov., 1960) was a woman physician
(Francis Kelsey, M.D.) whose physician/pharmacist husband did not
like the way routine pharmacologic tests had been done on
thalidomide.  Dr. Kelsey was also concerned about some medical
reports in late 1960 that thalidomide might cause neuropathy in
some of its users.  Neither of these concerns was fatal for the
thalidomide application, but together they were enough to hold up
the FDA's approval of thalidomide for a year.  Since neither
problem had anything to do with birth defects, it was only by the
sheerest chance that the red-tape in these matters caused intro-
duction of thalidomide to be delayed in the U.S. until it began
to be suggested in late 1961 that thalidomide was a dangerous
drug for pregnant women.  In the end, the association between
thalidomide and birth defects was discovered in Europe, not
America-- and certainly was not discovered by the FDA.  Despite
this, on August 7, 1962 a grateful President John F. Kennedy
awarded the Distinguished Federal Civil Service Award to Dr.
Kelsey, who by this time was beginning to make (in retrospect)
statements about how she had been concerned with the reproductive
safety of thalidomide all along.

    However much we all like heroic tales and medals, there is
actually very little in the record to bear out the official
heroic version of the thalidomide story.  Upon careful examina-
tion it appears that no reproductive tests were done at all on
thalidomide before 1961, nor indeed did the FDA ask for any.  In
fact, it appears that even had any pre-marketing reproductive
tests of thalidomide in rats been done, they would have *still*
have shown negative results, for thalidomide (as it turned out
later) does not cause birth defects in rats.  We now know that it
would have taken a much more exhaustive set of animal tests to
catch thalidomide than was routinely used anywhere in 1961.  An
honest reading of the facts thus forces the conclusion that
(questions of luck aside) Dr. Kelsey's medal was awarded basi-
cally for being a delay-causing bureaucrat and thereby allowing
Europeans to serve as first-class "guinea pigs" for Americans, in
a case where (quite literally) guinea pigs themselves would not
have done an adequate job.  Dr. Kelsey's medal was soon to become
an excuse for much self-congratulation regarding FDA policy,
without much thought being given to what the consequences of a
de-facto U.S. marketing delay policy might be, if applied to all
new drugs across-the-board.

   And there was other fallout.  In 1962 the thalidomide disaster
gave unexpected new life to several stalled bills on capitol hill
which proposed to give the FDA power over not only safety, but
also the _efficacy_ of new drugs.  There was a some irony in
this, since the thalidomide disaster itself was of course an
issue of safety, and had nothing at all to do with efficacy (the
bills were themselves introduced before anyone had heard of
thalidomide).  Unfortunately, however, the fine distinction was
lost on congress, which only knew that the FDA seemed to be a
good thing and should therefore be made bigger.  In 1962 the so-
called "Kefauver Amendments" to the Food, Drug and Cosmetic Act
were passed into law, giving the FDA new broad powers, and thus
the bloated and mutated regulatory agency that we know today was
born.  Thalidomide, as it turned out, proved to be a monster--
producing drug in more ways than one.

   Today, thirty years later, the cost of developing and market-
ing a new drug in the United States has risen to an average of
about a quarter of a billion dollars PER DRUG.  To make a long
story short, a large part of this money is regulatory cost.  Not
surprisingly, the huge sums spent in drug development are re-
flected in the price which the consumer pays when he/she picks up
any prescription for a newer drug.  The reader who wishes to
directly assess the regulatory cost of the FDA is invited to shop
for pharmaceuticals in Mexico, where (except for packaging) the
identical pharmaceutical product made by the identical company
can sometimes be had for as little as 1/5th the U.S. price.

   The FDA is responsible for high regulatory costs in money; the
regulatory cost in lives is more difficult to assess, but is
probably significant.  The high cost of drugs has led not a few
impoverished patients to stop taking what the doctor ordered,
sometimes with expensive or even tragic results.  Even worse, the
newest drugs now, as a rule, are available in Europe for years
before being available in the U.S., and in the interim many U.S.
patients almost certainly die for lack of treatment.  One
estimate, for instance, puts the number of people who died of
cardiac arrhythmias, as the direct result of the historical FDA's
multi-year lag-time in evaluating beta-blocker drugs, in the
hundreds of thousands-- a number which, if correct, makes up for
thalidomide many times over.

   It is important to understand that this situation arises via
one of the significant shortcomings of democracy.  Politically,
the FDA comes under severe pressure for passing a drug which is
later shown to be unsafe, but (in an unbalanced way) comes in for
much less political pressure as regards the equally dangerous
failure to swiftly pass a drug which proves to be efficacious.
This lack of balance results from the fact that patients who die
as the result of a drug-reaction are seen to die because of the
drug, but patients who die as the result of lack of a drug
(especially one which the local docs are not familiar with) are
seen to die of the *disease*.  Even if the local doctor under-
stands the FDA's role in preventing the patient from being
properly treated, "Stenosis of the Government" is not a medical
diagnosis, and cannot be written on a Death Certificate.

   It is also important to understand that this situation arises
because of a certain laziness of the citizenry in understanding
that the decision of whether to take a specific drug for a
specific purpose, is only partly a scientific one.  The reason
for this is that, even in the rare case where the probabilistic
risks and the benefits of "taking the drug vs. not taking it"
have been fully defined by science, the *balancing* of these
risks and benefits is still an ethical and moral decision, and
one which varies wildly from person to person, due to circum-
stance and personal preference.

   To put it succinctly, the decision to try a new and possibly
dangerous treatment may well and properly be influenced by how
much pain the prospective treatment-taker is in, and even upon
how soon he or she can expect to die if nothing is done.  Unfor-
tunately, however, these factors do not directly enter into
decisions made in Washington, basically because Washington is not
in pain, and Washington is not dying.  If you are the patient
with a serious problem, therefore, you may expect that having a
decision about your treatment made for you in Washington is less
likely to be satisfactory, if for no other reason simply due to
the fact that they do not know you or your problems in Washing-
ton, and even if they did know you, still could not care about
your problems nearly so much as you and your family do.  Empathy
is a function of proximity; all physicians know this.  It is an
elementary principle of medicine that nearly any displacement of
medical decision-making away from patient and physician in the
direction of a place thousands of miles away, is bound to result
in needless suffering.  Thus, the FDA as it functions today is
basically engaged in an evil enterprise.  To be sure, the people
who run the FDA may not be evil people (though perhaps some are)
but unfortunately, this does not change the facts about the FDA's
generally negative impact upon the world.

   The FDA, it must be remembered, is in the game for the
political power, not for the benefit of the citizenry.  This is a
fact which comes across in many issues, large and small:

*  In large health issues, the FDA is known to bow to political
pressure if it is massive enough (i.e., the AIDS lobby), but
there are very few fatal diseases in which those struck by the
disease are characteristically young and full of energy (which
can be used for lobbying) for many years before they succumb.
The FDA as an institution is thus free to remain firmly en-
trenched to retard development of treatments for hundreds of
equally deadly diseases which have smaller or weaker groups of
victims, by comparison with AIDS.  Alzheimer's disease patients,
for instance, do not ACT UP.

*  In small health issues the FDA's basic unconcern for health is
neatly illustrated by the fact that the FDA will not permit any
information about the possible dangers or side-effects of
particular herbal preparations to be printed on the bottle label,
even though such warnings might do much good.  This is because
the FDA does not want to set the precedent of providing usage
information of any kind on herb bottle labels.  The safety of the
consumer is secondary to the politics of the issue.

   A full discussion of the FDA's many failings on specific
issues is beyond the bounds of this essay, but there is room for
a last informative illustration.  For more than ten years the FDA
has zealously prohibited vitamin companies from making claims
about the ability of the B vitamin folic acid to prevent certain
birth defects, even while evidence in favor of this hypothesis
mounted year by year.  Finally, this year (1992) the American
Society of Pediatrics, in the face of overwhelming scientific
evidence, formally recommended that all women of childbearing age
(whether known to be pregnant or not) routinely take a folic acid
supplement pill.  Incredibly, as of this writing, the FDA will
still not permit vitamin manufacturers to inform the public of
this on the bottle label (!)  Since there now appears no place
the FDA can hide on this issue, however, it now seems likely
that, rather than admit a health claim for a vitamin pill, the
FDA will instead soon *mandate* adding folate to white flour, as
part of the enrichment process.  We thus seem likely to go very
soon from a situation where manufacturers are prohibited from
telling of the benefits of the vitamin, to one in which manu-
facturers are *obligated* to add it to your food without your
request (perhaps still without being allowed to tell you why).
Going from "prohibited" to "required" without going through the
intermediate state of individual choice is a nice illustration of
the way our government thinks, to be sure, but in the meanwhile,
until all this is sorted out and everyone is forced into the
"correct" mode, more children will surely be born deformed
because their parents meanwhile lacked information on supple-
mentation.  Once again, however, the mission of the FDA is power,
not the prevention of birth defects.  Anyone who still thinks
otherwise did not learn the right lesson from thalidomide.








May be reprinted without permission, if reprinted whole.
(c) 1992  Steven B. Harris, M.D.
Compuserve 71450,1773
310 825-1927
Comments: Gated by NETNEWS@AUVM.AMERICAN.EDU