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The
Canadian Society for Diabetic Rights
Presentation to Standing Committee on Health:
Feb. 03, 2003
Thank you for allowing us to appear before
the Standing Committee on Health today. We
represent The Society for Diabetic Rights,
formed two years ago to work for a strategy to
retain natural animal-sourced insulins in
Canada. We have about 250 members from
Newfoundland to British Columbia. We have more
members than money – we all work as volunteers
to inform physicians and people with diabetes
about the problems we and many others experience
with synthetic – or “human” – insulin.
Our goal is to see a national strategy in Canada
to ensure a secure, affordable and
domestically-accessible source of natural animal
insulin, both beef and pork.
We are
asking the Standing Committee on Health to hold
full public hearings on the experiences Canadian
diabetics are having with synthetic insulin. The
main questions we would like a public hearing to
address are:
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How many Canadian
diabetics experience adverse reactions
to synthetic insulin, including
hypoglycaemia ( hypoglycemia , insulin
shock, insulin reaction ) unawareness,
severe and frequent hypoglycaemia (
hypoglycemia , insulin shock, insulin
reaction ), memory loss, skin rashes,
weight loss, edema, anemia,
arthralgia-arthritis-myalgia syndrome
and other allergic reaction?
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How accurate are
product monographs?
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What steps has
Health Canada taken to increase
awareness of the availability of pork
insulin as a safe and viable treatment
option, and a preferred treatment for
those who experience adverse reactions
to synthetic insulin?
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How
is Health Canada addressing the problems
reported by diabetics using the Special
Access Programme to obtain beef or pork
insulin from the United Kingdom or
Brazil, including the unfair burden
imposed because of added costs?
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What
is the best national strategy to ensure
that Canadian diabetics can obtain
natural animal insulins – both beef
and pork – readily in any pharmacy in
the country on the same basis and at the
same cost as synthetic insulins?
In July 2002
we also asked the Standing Committee to
investigate ways to raise awareness about
synthetic insulin hypoglycaemia ( hypoglycemia ,
insulin shock, insulin reaction ) unawareness
among physicians and within the diabetes
community. We continue to see a great need to
develop information for the public, diabetes
educators, pharmacists and the medical community
about these and other side effects associated
with synthetic insulin. We believe Health Canada
should encourage people with diabetes,
physicians, pharmacists, diabetes educators and
other health professionals to report suspected
adverse reactions to insulin.
We also are
concerned about the influence of insulin
manufacturers on medical education, on Health
Canada and on physicians and diabetes educators
who advise patients about the most appropriate
insulin treatment. In addition, we believe that
physicians should have to disclose any conflict
of interest to their patients when advising them
about insulin treatment options. At the very
least, those who publish insulin treatment
guidelines should be required to list any
potential conflicts of interest associated with
the author.
These are the
main points we raised in our letter to the
Committee on July 2, 2002. In our presentation
today we will address the reasons that support
our request.
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There is a wide
schism between the claims about the
advantages associated with synthetic
insulin and the actual experiences
reported by many diabetics both in
Canada and worldwide.
When
the first synthetic insulin was being tested,
doctors involved in clinical trials for Eli
Lilly said this new type of insulin would help
reduce the incidence of long-term complications
of diabetes by controlling blood glucose levels
more effectively. But even the most ardent
supporters of synthetic insulin said it should
be used only on appropriate patients (those with
allergies to natural animal insulins) and that
transferring patients “en masse” would be
inappropriate.
In 1993
or 1994, Novo Nordisk succeeded in getting its
new insulin product, Novolin, approved by Health
Canada. A year later, it withdrew all of its
animal insulin products from the Canadian
market. At that time more than one-third of all
diabetics – roughly 45,000 people – used
animal insulin and, according to Eli Lilly, 95
percent of these used Connaught-Novo brands.
Thus, Canadian diabetics were switched “en
masse” to synthetic insulin between 1994 and
1995.
Canadian
diabetes patients learned either from their
pharmacist or their physician that Connaught-Novo’s
natural animal insulin was being withdrawn and
that they would have to start using “human”
insulin. Most were told by their doctors that
“human” insulin was better than animal
insulin because diabetics experienced fewer
allergic reactions to it. “Human” insulin,
doctors said, was safer, better and “identical”
to the insulin naturally made inside the human
body. Those diabetics who resisted switching
were told that all animal insulin was being
withdrawn from the market and they would have to
roll with the times. Most diabetics were
switched to humulin, made by Eli Lilly. If they
complained to their doctors that they were
unable to achieve stable blood sugar levels,
that they couldn’t tell when their blood
sugars were low, that they generally felt ill,
they were simply told they would have to “persevere”,
that they had no choice.
Diabetics
who contacted Health and Welfare Canada in the
mid-1990s to complain about Novo Nordisk’s
decision and to report problems using “human”
insulin were told to work more closely with
their doctors. Doctors, the Health Protection
Branch advised, should contact Novo Nordisk “to
find solutions for patients having concerns or
difficulties with the transfer from beef-pork
insulins to human insulins”. [Letter to Mrs.
G. Mushet from the Health Protection Branch,
June 26, 1995.]
In
1989, The Economist noted that Humulin, Eli
Lilly’s synthetic brand insulin, was causing a
“peculiar reaction” in diabetic patients.
“But why, no one knows”, the article said.
Three years later 400 diabetics in Great Britain
came together to launch a class action lawsuit
against Novo Nordisk and Eli Lilly, claiming
harmful effects from using synthetic insulins.
This attempt collapsed after two Novo Nordisk
sponsored studies were published disputing the
litigants’ claims. Six years later, Suzan
Kawulok, an American woman, launched a class
action lawsuit against the two companies
claiming she and others had been inadequately
warned about severe side effects, up to and
including death. We do not know the status of
this lawsuit.
In
1996, the US Food & Drug Administration
listed Humulin insulin as the 8th
most reported drug for adverse reactions.
MedWatch reported in early 2000 that over a
period of two years, 1998-1999, inclusive, 4,000
adverse events were reported with synthetic
insulins as a suspected primary or secondary
agent. These events included 150 deaths, 144
automobile accidents and 1,400 hospitalizations.
The most commonly reported adverse event
involved hypo- and hyperglycaemia “drug
ineffectiveness".
Adverse
event reporting has been widely recognized as an
under-utilised tool in Canada’s system of post
market surveillance. Estimates vary, but the
rate of reporting is between one percent and ten
percent of actual experience. As of December 30,
2002 there were over 630 adverse reactions
reported to the Marketed Health Products
Directorate – up from approximately 450 in
February 2002. These include 9 deaths.
Our
society has received reports from all of our
members and some of these have also been
reported to the MHPD. We have received reports
of 11 deaths. Two families in our group
represent young women with severe and
irreversible brain damage caused by night time
hypoglycaemia ( hypoglycemia , insulin shock,
insulin reaction ) and seizures. Many of our
members are permanently disabled and unable to
work because of their inability to avoid severe
and frequent hypoglycaemia ( hypoglycemia ,
insulin shock, insulin reaction ). One of our
members represents a group of approximately 140
Ontario families with one or more children who
have diabetes. He reports that approximately
one-quarter of the children in these families
are unable to identify an insulin reaction when
it occurs. Many also report frequent and severe
hypoglycaemia ( hypoglycemia , insulin shock,
insulin reaction ), blackouts, memory loss,
lethargy and inability to focus or concentrate.
The
most common complaints associated with synthetic
insulin are loss of control over blood sugars,
unexplained fluctuations, hypoglycaemia (
hypoglycemia , insulin shock, insulin reaction )
unawareness, increased severity and frequency of
hypoglycaemia ( hypoglycemia , insulin shock,
insulin reaction ) including blackouts and comas
(insulin shock), inability to focus or
concentrate, memory loss, myalgia or
arthritis-type symptoms, edema, anemia,
depression, severe and rapid weight loss,
vomiting, diarrhoea, skin rashes.
The
quality of life for diabetics trying to survive
on synthetic insulin is low. Many report they
are afraid to sleep at night because they don’t
believe they’ll wake up in the morning. Those
with young children report they must train their
children to rescue them if they black out
unexpectedly. Many who are grandparents report
that their kids don’t want to leave the
grandchildren with them because of their
frequent blackouts.
This is
no way to live, and it is, in many – perhaps
most – cases, unnecessary.
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There is a wide
schism between what the manufacturers
claim and what the evidence suggests.
Letters
from Eli Lilly and Novo Nordisk to our members
state that antibodies are associated with animal
insulin. Diabetics who reported that animal
insulin lasted longer than synthetic brands were
told they were likely producing antibodies to
the animal-derived insulin they were using.
These antibodies, according to Novo Nordisk, “can
extend the duration of the insulin by binding
the insulin in circulation”. Customers were
also informed that antibodies can cause problems
at injection sites. According to Novo Nordisk
“these reactions are seen with insulin usage
but rarely or never when using human insulin”.
[Letter to Dr. Francine Goulet from Dr. Anders
Bogg, Director of Medical Affairs, Novo Nordisk
Canada, July 21, 1995.]
According
to Eli Lilly, “Animal insulin is a foreign
substance in the human body. It produces
antibodies when used in humans, that is, the
body recognizes it as a foreign protein. That is
why human insulins were invented and brought to
the market in Canada in 1983. Human insulin,
known as Humulin, is identical to the insulin
that is contained in the pancreas of people
without diabetes”. [Letter to Helga Kelnor
from Mark Fleming, Manager, Lilly Diabetes Care,
July 8, 1996]
One of
our members who contacted Eli Lilly in 1999 to
express concern about the withdrawal of
beef-pork insulin products was told that some
patients experienced problems “when
transitioning from animal-derived to human
insulin”. A number of factors, she was told,
are involved: “people taking animal insulin
develop significant levels of antibodies against
that insulin…[which] may attenuate and buffer
the activity of injected insulin. When switching
to human insulin, these antibodies significantly
and rapidly decrease and may even disappear
entirely”. [Letter to Mrs. Marie Fitzgerald
from Donna R. Loughbridge, RN, Medical
Information Associate, Eli Lilly Canada, Inc.,
April 21, 1999]
In July
2002 The Cochrane Review published the results
of a thorough review of randomised controlled
trials of human versus animal insulin. Its
review (Richter B, Neises G. 'Human' insulin
versus animal insulin in people with diabetes
mellitus (Cochrane Review). In: The Cochrane
Library, Issue 3, 2002. Oxford: Update Software)
found that “At the time of introduction of
human insulin, marketing strategies suggested
that the lower immunogenicity of human insulin
and the anticipated decline in antibody titres
would offer a clinical advantage for insulin
treated patients”. However, these claims were
disputed as early as 1988. According to Richter
and Neises, “The studies on immunogenicity of
human and animal insulin were difficult to
compare because of the different assays for
insulin antibodies. Overall, depending on the
duration of follow-up, a decline in insulin
antibodies was observed following transfer from
animal to human insulin. This tended to level
out in studies of six months and longer
follow-up, rarely demonstrating significant
differences at the end of the trial” [pp.
10-11]
The
claims human insulin did not produce antibodies,
or that it produced fewer antibodies, are not
supported by the studies reviewed by the
Cochrane review. The association of rDNA insulin
with the human insulin produced in the pancreas
of non-diabetics is not accurate.
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There is a schism
between the information issued by Health
Canada and both the adverse reports
filed by Canadian diabetics and the
conclusions of the Cochrane Review.
The
Marketed Health Products Directorate has
dismissed the concerns of many hundreds of
Canadian diabetics who have reported their own
experiences, or those of their children,
spouses, siblings or parents. It is probably
safe to say that the response of Health Canada
and the MHPD (and the Therapeutic Products
Directorate before April 2002) has discouraged
many from reporting in the first place. Health
Canada has described our dilemma as an issue of
“choice” on the market, and advised us it
cannot force a company to produce a product it
doesn’t want to produce. While we support
choice of insulin, we feel our concerns are
related to our health and not our options as
consumers.
In May
2002, Health Canada issued a bulletin entitled
“The Safety of Human Insulins”. It stated
that “"human [sic] insulins have largely
replaced animal insulins because they are more
effective and have an excellent drug safety
record, both in Canada and in other
countries." The Cochrane reviewers found
that, on the contrary, the evidence indicates
synthetic insulin is not "more
effective". Health Canada seems to be
unaware of the reporting history associated with
synthetic insulin products in the United States
and Great Britain.
Health
Canada’s bulletin also states that "The
major advantage of human insulins is that there
are fewer anti-insulin antibodies formed than
with animal insulins. This means a lower risk of
adverse allergic reactions and a lower
possibility the patient will need higher and
higher doses of insulin."
Not
only is this assertion is also contradicted in
the Cochrane review, it is also contradicted by
the experiences of our members. It is estimated
that between one percent and three percent of
diabetics who used animal insulin prior to the
introduction of Humulin experienced allergic
reactions. Estimates vary, but many suggest that
a similar number, at least, are allergic to
synthetic insulin.
Health
Canada’s bulletin claims that "Prior to
human insulins being approved and marketed in
Canada, a thorough review of their effectiveness
was done. The results of clinical trials, some
conducted in Canada, were studied and
post-marketing experiences from other countries
were examined. The conclusion was that the
benefit-risk balance of human insulins was
appropriate."
This is
an alarming assertion. The Cochrane Review found
that “most studies were of poor methodological
quality” and that “None of the studies
assessed diabetic complications,
diabetes-related mortality or total mortality,
health-related quality of life, costs or
socio-economic effects”. Diabetes-related
complications include retinopathy, nephropathy,
neuropathy and increased risk of cardiovascular
disease. The reviewers concluded that “The
story of the introduction of human insulin might
be repeated by contemporary launching campaigns
to introduce pharmaceutical and technological
innovations that are not backed up by sufficient
proof of their advantages and safety”.
Conclusion
There
is no evidence that synthetic “human”
insulin is better or safer than animal insulin.
There are few reliable studies that indicate
what the experience of diabetes patients is with
hypoglycaemia ( hypoglycemia , insulin shock,
insulin reaction ). The estimates of how many
people experience adverse effects from using
synthetic insulin vary from three percent among
endocrinologists in Canada, to 20% by Diabetes
UK, to 53% by Swiss endocrinologists. Recently
the Swiss health minister, Dr. Thomas Zeltner
(his proper title is Director, Federal Office
for Public Health, Switzerland) wrote to
outgoing director of the World Health
Organisation, Dr. Gro Brundtland to ask her to
address “what steps might have to be taken to
ensure the future production of porcine insulin
on a global level”. Dr Zeltner estimated that
at least 10 percent of diabetics required animal
insulin to survive.
Low
blood sugar is a side effect of insulin use. The
confusion arises about whether severe and
frequent hypoglycaemic events are an acceptable
and necessary consequence of insulin treatment.
We say no, it isn’t, as long as animal insulin
remains on the market.
hypoglycaemia
( hypoglycemia , insulin shock, insulin reaction
) during the transition
from animal to synthetic has been the focus of
most of the clinical trials comparing synthetic
and porcine insulins. This leaves a gap in
information about those who never used animal
insulin. More research is required to determine
why some people see their weight drop to 75lbs.
or 85lbs. for no reason, why we experience
unexplained bouts of vomiting and persistent
diarrhea. There is no question that the effects
of human insulin on our quality of life and on
diabetes-related complications and mortality
have not received adequate attention.
Until
these questions are answered Health Canada must
respond to the reports of adverse reactions by
patients who report to the MHPD and ensure we
have access to animal insulin in Canada. We ask
the Standing Committee on Health to support a
public hearing to more fully understand the
situation so that a strategy to ensure animal
insulin is available at the local pharmacy is
developed.
Thank
you on behalf of our members for allowing us to
address the Committee.
Colleen
Fuller, President and Brenda Johnson, Vice
President
Society
for Diabetic Rights |