MR. SIEGNER:
Good morning and welcome. My name is Wes Siegner, I'm a partner
at the law firm of Hyman, Phelps & McNamara. This briefing
for the media is to discuss the FDA's, the Food and Drug Administration's
upcoming release of new adverse event reports concerning dietary
supplements that contain ephedra. Ephedra is an herb that
has been used for 5,000 years in China and is currently and
widely distributed in the United States primarily for weight
loss, energy and other purposes.
Before
I move on, I want to very briefly explain a couple of terms
and the experts can deal with this later. But you'll hear
some terms today: ephedra, ephedrine, ephedrine alkaloids
and ephedra alkaloids. And I just want to explain to you what
that is.
Ephedra
is, as I said, an herb. Ephedra contains ephedrine alkaloids,
which include ephedrine, pseudoephedrine and other alkaloids
that are naturally found in plant materials. In the early
1900s, medical uses for ephedrine were discovered and the
original ephedrine was extracted from the plant. Since then,
companies learned to synthetically manufacture ephedrine.
So the ephedrine that is today present in over-the-counter
drugs is actually the chemically synthetic ephedrine. There
are significant differences between the ephedra and chemically
synthetic ephedrine.
This
briefing is sponsored by the Ephedra Education Council, which
is a newly formed group, and the Council for Responsible Nutrition,
which has been in existence since 1973. The Ephedra Education
Council is composed of members of the Ephedra Committee of
American Herbal Products Association.
The
Council for Responsible Nutrition I'm sure many of you are
familiar with. They represent more than 100 companies in the
dietary supplement industry.
Now
the focus of the briefing today is again this release of adverse
event reports tomorrow by the Food and Drug Administration.
We understand that FDA has collected adverse events over a
period from June of 1997 to March of 1999, and that they have
collected approximately 140 adverse event reports that they
believe are connected in some way to the consumption, or may
be connected in some way to the consumption of ephedra.
Measured
against the rising sales of these products, what is the scientific
meaning of these adverse event reports? That is what we want
to discuss today. It is not our purpose to debate the need
for appropriate regulations of ephedra products. Everyone
agrees, including industry, that there's a need for appropriate
regulations, including serving limits and recommendations
against the use of these products by minors. Everyone agrees
that we need vigilant enforcement by the Food and Drug Administration
of today's existing laws.
The
primary issue here is the safety of ephedra when it's appropriately
labeled and properly consumed. And that's an issue that both
the FDA and industry have vehemently disagreed over for several
years now.
Tomorrow's
news will raise questions in the minds of millions of consumers
about the safety of ephedra. Our panel of experts has been
assembled so that we can educate the press and you can educate
the public as to the real issues pertaining to these products
and the meaning of these adverse event reports.
Before
turning to the panel I thought I could give you a little background
information of what brought us here today. In 1997, FDA published
a proposed rule to regulate ephedra products. And that rule's
really been the subject of several years of controversy. The
rule sought to impose very drastic limits on serving amounts
for ephedra products, also drastic limitations on the duration
of use of these products, limiting to seven days of use, and
also sought to prohibit the use of these products for weight
loss.
Essentially,
in industry's view, this proposal amounted to a ban on ephedra
products and the entire ephedra category. FDA, in its preamble
to the proposed rule, stated that the primary basis for the
proposed rule was the over-800 adverse event reports that
the FDA had collected over a period of several years. FDA
also stated in the preamble to the proposed rule that it had
relied on just 13 of those over-800 reports in order to set
a serving limit for these products. It's the validity of this
approach that we will address here today.
In
1999, the General Accounting Office issued a report that was
highly critical of the scientific basis for FDA's proposed
rule. The GAO found that there really was no scientific basis
for using the adverse event reports in the way that FDA had
used, particularly with respect to the use of the 13 to set
the serving limits. As a result of this and other actions,
FDA last month announced that it was going to withdraw the
dose and duration limits from the current proposed rule. And
we expect that tomorrow in the Federal Register FDA will formalize
that announcement.
I
want to be clear that industry has sought a different path
than what we're seeing here in terms of how industry and FDA
are working together. We tried to encourage FDA to work cooperatively
with industry to give industry the adverse event reports so
that industry could have a thorough and scientific review
of those reports done and given to FDA before FDA went forward
and issued an analysis to the public.
FDA
has declined to work with industry in that way. Instead, in
an approach that I believe shows clearly that there is really
no significant public health issue here, FDA has chosen to
withhold the adverse event reports from the public and industry
for more than two years and to go forward and do its own analysis
of those adverse event reports and release it to the public.
And that's what we're expecting will occur tomorrow. Industry's
cooperative approach was supported by all of the major trade
associations of the dietary supplement industry, also by the
U.S. Small Business Administration and several members of
Congress. And you have materials in your packet concerning
those issues.
Millions
of consumers have safely used ephedra products over the years.
What you will hear today from these scientific experts is
again, the meaning of these adverse event reports. And I think
we have with us people, experts who can explain as well as
anyone what the scientific meaning of these reports really
is. You will also hear today why experts who have reviewed
all of the scientific data objectively believe that when you
use ephedra properly and the product is appropriately labeled
according to industry standards that this product is safe.
Now,
that's the easy part of my job. The next part of my job, which
is holding these fellows to time limits so that you can all
ask questions at the end, is the most difficult part. But
I would like to introduce them all.
Next
to me here is John Hathcock, who is the vice president of
Nutritional Regulatory Affairs at the Council for Responsible
Nutrition. John has a very extensive background in toxicology
and was formerly at the Food and Drug Administration. Again,
you have materials in your packet, so I'm not going to go
into detailed explanations of their background here.
Ted
Farber and his partner, Norbert Page, are both principals
in a toxicology firm called ToxaChemica International. Ted
also has extensive experience in government service with both
FDA as a toxicologist and the Environmental Protection administration,
as does Norbert Page. Norbert is also a toxicologist and has
over 30 years of experience in this area.
Without
further delay, let me introduce John Hathcock, who is going
to give some background on what AERs are and what AERs are
not.
MR.
HATHCOCK: Thank you, Wes, and good morning, ladies and gentlemen.
In order
to look at the AERs that are coming out, in order to give
them some meaning with regard to the overall body of evidence,
it's very important to recognize what AERs are and also just
as important to recognize what they are not.
An
AER is simply a case report, one case report that comes into
the Food and Drug Administration. And it can come from a consumer,
from a physician, or from other sources. The contents of the
AERs, as they've been received by the FDA, can vary greatly,
from very terse, sparse, to voluminous and often sometimes
within that voluminous content, repetitive.
The
ability of delivery of detail, crucial detail varies greatly,
not depending on volume, but instead simply on whether the
particular investigator -- physician or other individual --
happened to address the crucial technical issues that are
necessary in order to give them meaning.
The
FDA's AERs -- adverse event reports -- for dietary supplements,
in general, and for ephedras in particular, simply accumulates
whatever reports it receives. And it does not send them through
any additional professional screening for content, for clarity,
for completeness or for continuity of the logic. The AER system
itself, what it is, is it's very faulty and it needs -- it
is in great need of repair. The Food and Drug Administration
has asked for a large increase in funding to help solve some
of its problems. These requests for fundings to fix the AER
system have come from Commissioner Henney and from Center
Director Levitt.
Also
the General Accounting Office has recognized that in this
report from last summer already mentioned by Wes that the
system has numerous shortcomings and limitations.
What
the AERs are not is just as important to recognize. Often
the AERs do not answer such basic questions as -- some of
them do not tell the signs or symptoms that were the basis
of the complaint. They simply say it was an adverse event,
generalizing without being specific.
Often
an AER will not answer the question what is the gender and
age of the person involved in the incident? Some are missing
information about the product and the manufacturer of the
product. Some are missing information. Many of them are missing
information about the dose, frequency and duration of consumption.
Many of them do not address the issue of about whether the
individual involved in the event had pre-existing health conditions
that may have precipitated alone or added to the susceptibility
to adverse events. Many of the AERs do not address whether
the person was consuming some other product or ingredient
or substance that could have caused the event or added to
the likelihood of an adverse event coming out.
No
matter how voluminous or complete an individual AER might
be, or even if they all were very detailed and complete, AERs
are not by themselves a sufficient basis for doing a safety
evaluation of a product or an ingredient. Because of their
basic nature, they cannot establish a cause and effect relationship
between the product and an adverse event. And they are not
adequate for a risk assessment; that is for a quantitative
assessment of the relationship. And in that regard, I would
direct you to the caveats, disclaimers, that FDA puts into
its website under the Center for Food Safety and Applied Nutrition,
its AER website. If you go into that and do a search for any
ingredient, the first thing pops up is a box of limitations
on use of the AERs. And one of those basically says you cannot
-- we have that as a handout, so I invite you to look at that
in some detail.
At
best, AERs represent only one-half of a case-controlled study
as an epidemiological scientist would describe it. What's
missing in the AERs is the comparison to the populations who
did not consume the products: what was the disease or event
rate in that population and how does it compare? And is there
any evidence whatever for causality?
In
summary, then, I would say that a full risk assessment for
safety evaluation of a substance must address all relevant
available scientific evidence including clinical trials, metabolic
studies, published case reports, as well as the FDA's AER
system. All evidence from all those sources should also be
subjected to the causality criteria that's been established
by the National Academy of Sciences.
Thank
you.
MR.
SIEGNER: Thank you, John. Our next speaker is Ted Farber.
He is going to talk briefly about the 1997 proposal and the
use of the AERs in support of that proposal, and also the
General Accounting -- the GAO report. Ted.
MR.
FARBER: Thank you, Wes. Thank you, ladies and gentlemen.
If you
would refer to the folder that you have from the Ephedra Education
Council, I'm going to refer you to some handouts that I have
in the folder. The first handout is entitled "Docket 923 AERs."
Over
a year and a half ago, Wes Siegner of the law firm of Hyman,
Phelps & McNamara asked our firm to analyze the adverse
effects database assembled by Food and Drug in regards to
ephedra containing herbal products. This AER database comes
from an unfiltered telephone hotline set up by the Food and
Drug Administration to receive largely anecdotal information,
primarily from non-medical sources. Approximately 20 percent
of the reports in this database were actively recruited by
the Department of Health down in the state of Texas and largely
cover one product which has been removed from the marketplace
several years ago.
Now
based largely on these AERs, as Wes had indicated, the FDA
issued a proposed rule that has -- would have effectively
removed ephedra-containing dietary supplements from the marketplace.
My partner and I, Dr. Norbert Page and myself, have spent
over 700 hours carefully examining each and every report in
the AER database. And I would like to share with you some
of the facts in terms of the almost total inadequacy and worthlessness
of this database.
If
you look at the first page of the handout, you can see how
the analysis of these 923 AERs lays out. Fifteen of the products
could not even be identified. There was no name associated
with the product. And 13 percent of the AERs are involved
with a product that does not contain any ephedra at all.
Almost
72 percent of the AERs were devoid of medical records. In
addition to that, there were significant deficiencies in regards
to dose level reporting, dose frequency reporting and duration
reporting. And not attempting to double-count in some of these
situations, the bottom line is that 85 percent of the database
is worthless, inadequate in terms of doing a causality analysis.
In fact, it's even higher than 85 percent, because we accepted
just a one-line sentence from a physician or a single paragraph
from a hospital as a medical record.
Now,
what about the adequacies of using this kind of database for
doing epidemiological projections and doing a causality analysis?
If you refer to the second page of my handouts, these are
official FDA caveats that appear in the docket associated
with the AERs. And I've emphasized the last two items there
in regards to the worthwhileness of the database. It states:
"Accumulated case reports should not be used to calculate
incidence or estimates of product risk. And occurrence or
incidence rates cannot be derived from AERs, only reporting
rates."
The
third page of my handout actually shows you that in violation
of their own caveats and accepted principles in our science,
the FDA went ahead and in fact did epidemiological projections.
These values are right out of the proposed rule, completely
improper in regards to what we've done. John has pointed out
that when you do an epidemiological analysis of even the simplest
form, you need four numbers. You need a numerator and a denominator
among the population that's taking the product. The only thing
Food and Drug has is a suspect number as the numerator. It
doesn't have a denominator, and it doesn't have a numerator
and a denominator to use in the general public that has not
been taking the product.
The
last thing that I would like to refer to on the handout is
just a few simple facts about Ma Huang ephedra. This is an
herb that's been used by the Chinese extensively. We're talking
about hundreds of millions of people over the centuries have
been treated with this herb. At levels three to 10 times greater
than the levels of ephedra and ephedrine that are found in
these herbal dietary supplement products, there has been no
report of adverse effects in our medical literature as well
as the Chinese medical literature at these dose levels.
Ma
Huang contains a number of ephedra alkaloids, one of which
is ephedrine. This was isolated 75 years ago. It's been extensively
used in Western medicine. We know what the pharmacology and
toxicology are, and the AER database is inconsistent with
what our experience is for the last 75 years.
I
don't know how many of you are aware of the fact that there
are over-the-counter products containing ephedrine, the principal
alkaloid in ephedra. Primatene is one. Bronchaid is another.
These asthmatics have been taking these products, some of
them probably for decades, along with the ubiquitous intake
of caffeine in coffee and cola beverages. There is no incidence
comparable to the incidence of AERs connected with ephedra-
containing products associated with Bronchaid and with Primatene.
Basically,
where are the bodies? Where are the cases in regards to these
products? They're not there. And it's a gross inconsistency
and an ideological situation that exists in regards to what
Food and Drug has been trying to do.
Wes
has just made note of the fact that perhaps another group
of AERs are going to be released by the Food and Drug Administration
tomorrow. We don't know really what the total number is, but
we've had an opportunity to preliminarily look at that database.
That database is still an inadequate database, and will not
materially change our opinion in regards to the worthlessness
of this system.
Thank
you.
MR.
SIEGNER: Thank you, Ted.
Our next
speaker is Norbert Page. Norbert's going to address the adverse
event reports that we suspect are coming out tomorrow. We
have obtained a copy a couple of weeks ago from the Hill.
Let me add a couple of caveats concerning that. We know that
the adverse events that FDA will release tomorrow are included
in this set. We're not sure exactly which ones they're going
to pick out of the set that we have reviewed.
But
nonetheless, the review that both John Hathcock has done on
behalf of CRN -- and we'll give a chance for him to talk about
that in a minute -- and Dr. Page and Dr. Farber have done
will include whatever sets that FDA releases tomorrow. So
Dr. Page's comments are relevant to that data set.
MR.
PAGE: Thank you, Wes. It's a pleasure being with you. As Wes
has indicated, we have started our scientific analysis of
this group of 140 of the AERs. And what I want to do is sort
of walk you through the process of how we're analyzing the
AERs and some of the things that should be looked for in doing
an analysis.
I
might mention to you that the type of analysis that we performed
is basically the hazard evaluation and the risk assessment
that's routinely used in federal agencies. Dr. Farber and
I have both had the responsibility of conducting risk assessments
for many years. And so I think we know the procedures quite
well.
Basically,
there are two steps to doing a risk assessment. You've already
heard a little bit about this. The first step is obtaining
reliable data, so that you can basically bring together critical
facts and a number of cases which can be analyzed. And then,
from this analysis, you go to the second step, and that is
to determine or ask the question: Are the instances of the
alleged effects greater than that expected in the non-exposed
populations?
John
has called that the Control Group, and that's what it's normally
referred to -- Control or Reference Group. Now the risk assessment
procedure involved is basically what's known as a weight of
evidence approach. This is gathering all the information and
weighing it.
Basically,
where is the beef?, what is the weight? Is there a risk? How
great is this risk? And does the risk outweigh the benefits?
This type analysis is needed for a scientific basis for any
government regulatory action.
The
federal review. Let me step back just a little bit and talk
about the process of evaluating individual reports. Because
I think that's very critical to this whole analysis. A number
of these issues have already been addressed, so I'll try to
go through 'em a little quicker.
First
of all, we look for exposure information. Was there indeed
consumption of ephedra? Was the product clearly identified?
Do we really know that the person had consumed the product?
If
we know this, then, let's then ask when was it consumed and
what was the dose-level, frequency and the duration? And on
this line, keep in mind that ephedrine does not remain in
the body very long. It leaves the body fairly quickly. That's
the reason asthmatics will take tablets four times a day,
just to keep their blood level up. And so this gets important
when you analyze the temporal relationship: how long before
the event was the product actually consumed, if it was?
I
can't emphasize more highly that exposure history is important.
Without an exposure, of course, any effects cannot be related
totally to that lack of exposure.
Second
point. Is the alleged effect biologically plausible? Let me
explain what we mean by this. Is the effect one for which
there is already existing clinical or laboratory data that
shows that the effects can be caused by the substance? I think
we all know that substances vary in their biological effect.
That's the way pharmaceuticals are directed toward one specific
organ or disease versus another.
I'll
give you one example of the current AERs. It involves a woman
that noticed that her abdomen was enlarged two weeks after
she started consuming the dietary supplement. It turned out
that she had an ovarian tumor, which was surgically removed.
However,
she submitted an AER, claiming that the supplement did it.
I think we all know that tumors don't arise that fast. It's
certainly not going to come up in two weeks. Tumors usually
take anywhere from many months to several years from the time
they start to becoming a clinical problem.
Now
one can only speculate that that woman's dietary plan may
-- she may have reduced her weight to the point now that the
abdominal swelling became noticeable. Chances are it was a
coincidence, that there's no relationship between the tumor
and the dietary supplement. However, we have an AER that has
been submitted alleging this. FDA did not filter this out
of the group of 140.
Okay,
the third point I want to get to is that there can be other
risk factors that should be considered. Now, to analyze for
this, we need two key types of information. Good medical histories
and the patients. And then also a good family history.
Let's
go into the medical history first. Medical history and records
can be quite revealing. It often shows that the alleged effects
in fact existed prior to the person's consuming the supplement.
Let
me illustrate this just a little bit. one situation. We've
seen a number of reports where individuals had pre-existing
hypertension, but they reported that they had hypertension
as a result of using a recent dietary supplement. You have
to take into consideration whether in fact there is a relationship
between the most recent exposure to the supplement, or was
it just by coincidence it just happened? It had no relationship
to the supplemental use.
Were
there other pre-existing risk factors, such as medicines that
were being taken at the time? I'm couching a number of questions
that we go through mentally in doing this analysis. Now was
the person obese and fasting? Was the person engaged in very
strenuous exercise programs? Was there an underlying medical
condition that should be considered, such as diabetes? Was
the person a smoker? What other products was the person exposed
to?
That's
about all I want to give as an overview. But I think what
I want to transmit is this is a fairly complex analysis that
basically has to be performed before we can give any type
of good credibility to the particular reports.
MR.
SIEGNER: Okay. We're running a little over on the presentations
here. And I don't want to deprive people of the opportunity
to ask questions. John Hathcock has some winding-up comments,
but I think that he best address those in the context of questions
from the press.
And
with that, why don't we take some questions and I can parse
them out. Go ahead. Yes.
Q
Dr. Hathcock, the news release from your organization says
that you have made a study. I wonder if you could tell us
if that study indicate any deaths? If so, how many? Or what
we would commonly refer to as serious illnesses? If so, how
many? And your analysis? Would you share with us the details
of your analysis?
MR.
HATHCOCK: The 140 cases represent everything from reported
diarrhea followed by constipation to death. We recognize that
there are some 10 cases of fatalities, several of stroke and
other serious events.
When
you look at those with regard to the criteria for causality
and for compounding and missing data, we find often either
missing or even conflicting information about dosage. In one
particular case of a young man who had a seizure, while he
was being incapacitated by that, his wife asserted that he
took the product strictly by label, according to the label
instructions. After he had recovered somewhat, he acknowledged
that he had been taking a handful several times a day, and
that's a quote.
So
there's all kinds of information about various levels of adverse
events, ranging from trivial and non-specific to major. And
the issue is what is those rates among the general population
who is not taking the product.
Thank
you.
MR.
SIEGNER: Yes.
Q
I don't know exactly who should respond to it.
At the
hearing before Congress in 1997, either just before or just
after this new rule was proposed, the head of pharmacology
at Georgetown University Medical Center stated in the last
sentence of his remarks, of his testimony was that it is clear
that ephedrine or ephedra products cause some ventricular
or fibrillation, or some kind of rapid heartbeat that is very
dangerous, and that that is why dosage, or whatever, should
be eliminated.
Do you
agree with that? Do you recall what I'm talking about? I'm
not with the data, but the potential danger of causing heart
problems, rapid heart beat; for example, the kind that killed
Elvis Presley. Is that true that this product can do that?
Or do you completely reject the testimony of this doctor?
MR.
SIEGNER: Let me just frame the event, and then I think I'll
let Dr. Farber handle the question, because he was at the
event and also testified.
I
believe you're referring to a hearing before the House Commerce
Committee or Government Reform Committee that occurred last
May. And --
Q
No, I think this was prior. This was prior. This was not before
-- I don't know if it was prior --
MR. SIEGNER:
Okay. I believe the same individual -- Dr. Woolsey (ph) is
the individual --
Q That's
correct.
Q
I looked it up in my records. So I couldn't find it.
MR.
SIEGNER: Right. Okay. And I believe that I wasn't at the one
that you were talking about, but he's probably testified as
to the same information at the hearing that I was at and Ted
was at, Dr. Farber. So anyway, I understand, you know, who
it is and what was said. And with that, I'll let Dr. Farber
respond to the issue of whether this is medically plausible.
MR.
FARBER: The House Government Oversight Committee meeting which
was held in May of last year -- I testified at that hearing,
and so did Dr. Raymond Woolsey. My recollection of his testimony
-- he made a statement that as far he was concerned, there
was no safe dose of ephedra.
Q
That's correct.
MR.
FARBER: Congressman Burton asked me for my opinion in regards
to that statement. That's contrary to just about the most
basic tenet of the science of toxicology. And basically, to
sum it up, the dose makes the poison. Everything on God's
Green Earth has some toxicity associated with it at some dose.
But also, there's a safe level for everything in God's Green
Universe. And for somebody to make that kind of statement
basically indicates that he's way off base in regards to even
the most fundamental concepts in toxicology. I believe Dr.
Woolsey also served on the Working Force Committee, the second
one, that Food and Drug put together. This was the committee
that made the judgment in regards to what a dangerous level
of ephedrine was based upon 13 cases, six of which had no
medical records. And there were two deaths associated with
those 13, one of which was at an enormous dose level, certainly
not connected with the eight milligrams that they set as the
limit. And the other death there was caused by a product that
did not contain any ephedrine whatsoever.
MR.
SIEGNER: Other questions.
Q
What are some of the products that contain ephedrine? What
are some of the popular dietary supplements that have ephedrine
in it?
MR.
SIEGNER: Well, with respect to name brands that people would
recognize, there are products that are marketed for weight
loss, including -- I think probably the most widely known
is metabolites product and other products. There's also a
product -- products marketed through the GNC stores. It's
hard -- I don't want to pick out any single product. There
are really hundreds of these products available in health
food stores and in drug stores. And you know, the best thing
to do, in terms of getting samples, is to go out and get them.
Q
-- cough cold products? Most cough cold products available
OTC contain ephedra or ephedrine.
MR.
SIEGNER: It contains pseudoephedrine. The pseudoephedrine
is approved as a decongestant.
Q
Is that the same family or -- ?
MR.
SIEGNER: It's the same family of alkaloids, that's correct.
And ephedrine is actually used -- approved for use in nasal
topical decongestants also as products -- bronchial dilators
for asthma.
Q
Are they in the same category that's being discussed here?
MR.
SIEGNER: It's a different -- that's a different category.
They're regulated as drugs under the over-the-counter drug
monographs. They all contain synthetic ephedrine and pseudoephedrine,
whereas the products we're talking about are regulated as
dietary supplements -- not under the over-the-counter monogram,
but as foods and supplements.
Q
So metabolized GNC, weight loss products. Can you be anywhere
more specific?
MR.
SIEGNER: Weight loss products, energy products. Are there
other questions.
Q
Do you agree that there should be surveillance of these products?
And if so, how should the system work if it's not working
properly now?
MR.
SIEGNER: Well, I think there's two questions there. Yes, industry
is very much supportive of both surveillance, in terms of
having a good adverse event monitoring system. And the problem
right now that we have is that there's information going into
the system, but the information isn't being properly handled.
And most disturbing to industry and I think to the public
overall is you can't get information out of the system.
We
have had requests for adverse event reports into FDA for over
two years. And we have not received responses to those requests.
But also, with respect to the information-in, information-out,
FDA has a website which was part of this hearing last year
that Congressman Burton held. And the problem there is that
you have events posted on an Internet website, such as "death"
or "seizure" or "stroke" with a product named and ingredients
with no other information.
And
you can't -- you know, companies first become aware that there
may have been a report on their product by going to the FDA
website. But then they can't get the background information;
they can't find out more information in order to make any
responsible judgments. So, yes, we need a good monitoring
system.
The
other question you had is, you know, what do we do if it's
not working. Well, one of the things that we believe is that
the standards that industry has put in place have actually
worked. And you know, that will maybe come out as we evaluate
the AERs more and work with FDA on that. But the information
that's coming certainly into industry through their systems
is that there really is no significant level of adverse reports
with the products when they are properly labeled or properly
used.
Q
Could you repeat that last sentence?
MR.
SIEGNER: The last sentence. Is that our information is that
companies, through their monitoring systems -- and some of
these companies do have very good monitoring systems -- have
information that shows that when the products are properly
used and properly labeled that they are safe.
Q
If the system is in place, what is it that they need to do
more? More personnel to do the follow-up, to insure that all
of the boxes are ticked off on information?
MR.
SIEGNER: That's correct. We would like, when information comes
in, to have follow-up to get the boxes, as you say, ticked
off. FDA has always recognized that the system works best
when you get reports from health professionals, because they
know how to ask the proper questions, how to give the proper
information.
There
is a problem. You know, I don't think the system is going
to discourage consumers from reporting. But there is a problem
overall with consumer reports. They tend to be inaccurate,
incomplete and as Ted said, anecdotal. Sometimes you get reports
from friends or relatives where they really have almost no
information. But that gets chalked up as an adverse event
report associated with a particular product.
Also
obviously, we would like to see more attention paid to once
you get the appropriate information in make it accessible
to the public.
Q
-- so many more than 140. What is the time frame that you're
discussing?
MR.
FARBER: Well, this was the first batch of AERs that was utilized
by the agency to support the proposed rule. Initially they
--
Q
[Off-mike, inaudible remark.]
MR.
SIEGNER: I think it was approximately '93 through June of
'97.
MR.
FARBER: There were first 800 and some odd, and then some --
about 100 and some odd additional were added to the pile.
So we looked at 923 of them. And both Norbert and I looked
at every one of those, looking for the adequacy of the data.
And sort of kicking and screaming, we did our own causality
analysis, because - - I say kicking and screaming because
the database was so inadequate. We were scientifically reluctant
to do a causality analysis. But we did it anyway, trying to
do something with the data. And there is nothing there in
that first batch that alarmed us. And frankly, our preliminary
analysis of this 140 or 134 AERs really don't change our attitude.
Q
If you could just stay there for a moment. If I add these
numbers up very quickly, they look like they add up to maybe
about 2,000 AERs from '93 to '97. And now you're saying there's
only 140 that are the subject since 1997? Is that -- ?
MR. FARBER:
Well, I believe it adds up to 923. But now there's an additional
140 or 134. It's not on that list. We haven't analyzed that.
We've looked at it preliminarily. We have not had the time
to do the kind of detailed analysis that was performed in
regards to the 923.
MR.
SIEGNER: Let me just respond to the confusion on this chart.
The numbers reflected there aren't intended to add up to 900.
What that is a representation is out of the 900, how many
are missing medical records? How many are missing dosing information?
So you will get some that are missing both and add up to a
higher number.
MR.
SIEGNER: Yes, sir.
Q
Could you answer the question of the economics of this? Some
number or how much in dollars is spent in retail on these
type of products that you're talking about?
MR.
FARBER: I think Wes would be more the person to respond to
that question.
MR.
SIEGNER: We're in the process of gathering better information,
so the numbers I will give you are fairly -- fairly rough.
But our understanding is that there's somewhere in the neighborhood
of three billion servings per year of these products being
sold at this time. I would guess that the retail sales of
these products are in the neighborhood of several hundred
million to a billion dollars.
Okay.
I guess I'm being told we need to wrap up. Should I take one
more, or -- okay. Okay, yeah, and we'll stay behind and be
happy to answer further questions, sure.
Q
Two very short questions. The numbers 134 and 140 new AERs
have been thrown around. Can you be more specific as to which
number is accurate?
MR.
SIEGNER: Tell you exactly? I'm not sure we've done an AER
count. I'll let John answer that.
MR.
HATHCOCK: Well, one of us at the Council for Responsible Nutrition
was talking with a Center Director for Food Safety and Applied
Nutrition at FDA, and he used the nice, round number of 140.
I assumed he was generalizing, because when the records that
came to me add up to 134. So I don't know if he was rounding
off or if there's something that's a surprise.
Q
And as a follow-up to that, can you give us an idea of how
many different types of products were involved in those 134
-- ?
MR.
HATHCOCK: Some -- two products add up for about half of the
total. There's a wide scattering, and I don't have the number
of the -- the total number of the different products that
were involved, but certainly it must have been in the neighborhood
of a dozen or more.
And
the thing that is astonishing to me is that some of the individuals
were not only taking multiple products, but taking a huge
number of multiple products. One individual listed as taking
83 different products during the last year. I find that astonishing
financially, if not otherwise. (Laughter.)
MR.
SIEGNER: I guess that wraps it up. And again, we'd be happy
to stay around, and we will stay around to answer further
questions.
Thank
you.
[END OF
EVENT.]
