Examination of Witnesses (Questions 700
- 719)
THURSDAY 13 JANUARY 2005
MR EDDIE
GRAY, DR
STUART DOLLOW,
MR CHRIS
BRINSMEAD AND
DR JOHN
PATTERSON
Q700 Mr Jones: Moving on, most countries,
in fact almost all countries, do not allow direct-to-consumer
promotion of prescription medicines, although notably the United
States does, and your pharmaceutical companies are enthusiastic
participants in that in the United States, which is what you have
to be really within that system. Do you think that direct-to-consumer
advertising has much to recommend it to other countries?
Mr Brinsmead: I think my position
would be that we in this country are happy with the situation
and would not be pushing for direct-to-consumer advertising on
behalf of AstraZeneca anyway at this moment. I think what we would
think is important is that the provision of medical information
about a product to patients should be possible, so I think we
have to distinguish between advertising on television and in magazines,
that type of activity from providing information. The fact is
that if a patient wants to know about a drug or a disease, they
can go on to a website and they can use the search engine and
they will get lots and lots of information. It could come from
anywhere and the information may or may not be validated. I think
it is important that there should be some way whereby pharmaceutical
companies, who by definition have most of the information, especially
if it is a new product they have been researching, can make sure
that information is available to the patients, to doctors and
to the people who want to know about that.
Q701 Mr Jones: Mr Gray, since your
company operates in the United States and in this country and
other European countries, you would be in a good position to compare
and contrast the values.
Mr Gray: Yes. In addition, I was
personally living and working in the United States in the early
`90s when the DTCA all started. I think I learned from that that
any form of communication has to sit comfortably in the cultural
context. It was very interesting. The friends my wife and I had
when we lived there were the people who lived around us and parents
of children in the schools, so they were not industry people.
Some of them were doctors in the system. I have to say that those
people, pretty overwhelmingly, thought DTCA was a good thing.
They felt it was consistent with "American life" for
want of a better phrase. They wanted the information; they were
very, kind of, proactive about which doctor to go and visit and
all of that kind of thing. I think my sense of the UK is that
the cultural context is not appropriate for direct-to-consumer
advertising. I do not think the public want it and as an organisation
we are not pressing for it.
Q702 Mr Jones: Do you see, in this
country, sponsorship of selected patient organisations and disease
awareness campaigns as a substitute for direct-to-consumer advertising?
Mr Gray: I do not see it as a
substitute at all. I see disease awareness as a separate and valid
activity. I was talking earlier about the issue of: Do we invent
diseases and are we trying to stretch the criteria? and I think
another part of the element that has got mixed up in that is this
issue of whether there are also patients, kind of, being forced
or encouraged into the system who should not be. If you look at
the current attitude of the National Health Service and how at
the moment, particularly in primary care, with its focus and attention
on long-term medical conditions, the National Health Service is
actively looking and seeking to get patients in as early as possible
and that is to the benefit of the patients. If you look at the
current new general practitioner contract, for example, various
measures which lead to GP payment are around issues like: Do we
know if all these patients are in a particular condition? Do we
have a register of them? Are we seeing them ever so frequently
. . . on a certain frequency? et ceteranothing to
do with whether or not there is any treatment involved. Those
are important measures for the ongoing health of these long-term
conditions. The other thingwhich sometimes is a bit galling,
quite honestlyis that often the best balance of management
of a patient only really comes about if you can make the patient
aware and get them to access the system early. If I think about
diabetes, for example, everybody would say for Type 2 diabetes
that the first thing you do is a regime of diet and exercise.
Everybody says that, including us: it is on all our materials.
But of course the later a person actually is caught and presented
for Type 2 diabetes, the less successful diet and exercise is
and the accusation is: Why are they on drugs so quickly? Well,
actually, because they turned up too late. The earlier they turn
up, then the more successful that period of diet and exercise
and the more elongated that can be. We do take part in such activities.
I have one here: there is no promotion involved in it at all,
and we do have examples of people who have responded with words
of thanks on the basis of: "I read that and realised some
of those applied to me and I have gone and done something about
it"interestingly, including a member of parliament.
So it forms a valuable service, and I see it in isolation and
not as a substitute for anything, quite frankly.
Dr Dollow: If I could supplement
that and reflect on my experience. I used to be a hospital doctor
and a general practitioner, and, when you see patients coming
in who are informed, it enables you to have a debate with them
about their health. So many of the things in medicine are not
black and white, they are about making choices, and if patients
are informed about how to help make those choices they are engaged
with the management of their own disease. That has to be a benefit.
If, however, a patient comes in and you find they simply do not
have the disease, you can say, "Well, it's good that you
are aware of it, but you don't have it so I don't need to worry
about it." I think that individual doctor/patient relationship
has to be seen as the final and appropriate gatekeeper of the
information that gets to patients through disease awareness.
Q703 Mr Burns: Could I pick you up
on that point because there is also a counterview to that, which
is that there is a growing problem in the patient/GP relationship
because individuals are going into the GP practice, having read
some information from a variety of sources, including the internet,
and telling the doctor what is wrong with them. Then, when the
doctor examines them and does not agree, a blazing row ensues
because the patient believes that the doctor has got it wrong.
On the argument that a little education is worse than no education
at all, a lot of GPs are having serious problems with their relationships
with their patients.
Dr Dollow: All I can do is reflect
on my experience and the experience of friends and colleagues.
Q704 Mr Burns: With respect, how
long ago was that experience?
Dr Dollow: My experience was 14
years ago, but . . .
Q705 Mr Burns: That was before the
internet.
Dr Dollow: But friends and colleagues
who are currently in general practice I still talk to and I think
I can reflect on the discussions that they have had with me. There
are occasionally disagreements, but, in most cases, some patients
have been sent away, saying, "No, you haven't got that,"
and with some patients saying, "Yes, actually you have got
that and it is worth you doing something about it," which
may or may not require a medicine.
Q706 Chairman: As you have indicated
that you have looked at videos of previous sessions, may I raise
the evidence given to us by the Royal College of General Practitioners'
witness. You may remember, a practising GP spoke in some detail
about her concerns over the way in which, as a consequence of
the industry's marketing and, in her view, disease mongering,
she was faced with patients, particularly on the osteoporosis
issue, coming in with all sorts of concerns that she felt really
were completely wrong. She was very strong in saying that we are
into a climate now where people come in having had their minds
made up about their own health problems, and it creates immense
difficulties for people like her. Did you see that?
Mr Gray: I did. I think there
is a very pertinent kind of connection with the previous question.
Nowadays, I believe I am right in saying, health on the internet
is the biggest content behind pornography. From our point of view,
in terms of any disease awareness activity in which we have been
involved I am extremely confident that we apply to it exactly
the same standards that we apply to everything else. I think,
if you have looked at any of the health information available
on the web, there is a range from very respectable right down
to complete and utter cranks. Ours, as a percentage of the total
that is available, is actually really very small. So I do believe
you are probably right that many General Practitioners, as Dr
Heath, I think it was, confirmed in her own evidence, are experiencing
this problem, but the idea that it is a function of what we are
doing . . . I think the world has well moved beyond that. The
sheer amount of information on the internet now on health matters,
completely unregulated, I suspect, is much more a contributor
to that situation than anything in which we are involved.
Q707 Dr Taylor: Turning to research
and innovation, we have all seen a huge explosion of really important
new drugs over the last 40 years. There is a list as long as your
arm. The discovery of those sorts of huge innovations really seems
to have slowed down. Is this inevitable? What fields are you looking
at? We have had a very useful paper from the ABPI about polio,
river blindness, trachoma, HIV, tuberculosisall the things
in the less well-off countries. What sort of areas are you looking
at to increase the rate of innovation?
Dr Patterson: We look across,
we think, about 80% of medicine in the therapeutic areas in which
we research, so most of the areas that you would regard as key
priorities or the major causes of morbidity and mortality, but
no one company looks at all fields, for instance. Could I pick
up on that innovation has decreased. We have seen, in the last
few years certainly, a reduction in the number of medicines getting
to the market place, but I think amongst them are some very significant
and very innovative medicines. People fail to understand just
the length of time and the investment required to get them there.
Perhaps the best example I can give you is monoclonal antibodies.
They were discovered in Cambridge in the UK in 1976 but the first
medicines based on monoclonal antibodies only got to the market
place in 2000 and it is only now that we have, sort of, 10 or
12 of them out there and actually it is only now that the first
fully human monoclonalsbecause the early ones were antigenic
and could not be given multiple timesare beginning to come
through. So that is something like 30 years from their discovery.
During the 1990s a lot of the human genome work was undertaken.
Many exciting new things came out of that and somehow the world
expects instant gratification. I suspect, if I am still working
in this industry in 2015 and 2020 that gratification will start
to hit the market place, but if you add 10 years from when a medicine
is first discovered to get into the market place, to the science
that is required to turn a SNIP or a change into our understanding
of the genome into something that has become a medicine, you are
talking 20- to 30-year time periods. During the '90s, in addition
to all the classic organic chemistry, small molecule type work
that industry was doing, we had to add in all the new science.
We have finite resources too. Most companies diverted resources
into those things and as a result there was a slowing down of
some of the other small molecule work. I hope we are going to
see in the second half of this decade the fruits of some of those
labours beginning to speed up again and most of us would say our
early development portfolios, those products that are in pre-clinical
or phase 1 and 2, are now significantly greater than they were
five years ago.
Dr Taylor: Thank you. That is very clear.
Q708 Dr Naysmith: I am going to move
on to a subject which has been described to us as "pharmacovigilance"
although I am not sure what that term really means. Would it be
fair to say that, once drugs get licensed and are on the market,
companies typically spend a lot more time and money on demonstrating
their benefits than investigating and looking at their potential
harmful effects? Do you think that is true? If it is true, do
you think they have the balance right?
Dr Patterson: I think that is
an outrageous statement and it is not true at all.
Q709 Dr Naysmith: Not true at all.
Dr Patterson: I think we have
a legal, moral and ethical duty to follow the safety of our products
from the moment they go to the first patient through to the moment
we stop producing them or they stop being on the market place.
Our adverse reactions programmes and processes are global. We
have large numbers of people employed in our organisations whose
sole role in life is to collect, collate, examine and analyse
those activities. We have a thing in AstraZeneca called the SERM
process (the safety, evaluation, review mechanism). It is a community
of people who have nothing to do with the efficacy of our products
or nothing to do with the marketing of our products. They are
doctors and scientists and epidemiologists whose job is to review
the data on a regular basis to make sure there are no signals
coming out, there are no adverse reactions coming out, and then
to make sure that if we see those things they are dealt with appropriately,
either by, at the very extreme, stopping selling the medicine,
or changing the data sheet or informing health authorities. In
addition to that, we have regular safety update reports that we
make to the health authorities, and, again, depending on the severity
of the adverse event, we report either rapidly or on a periodic
basis. When a product is newly in the market place, we often have
more onerous needs than before. It is all there. We also monitor
not just everything that comes into us spontaneously but the world
literature for anything that is reported there, and we take every
regulatory authority worldwide database and feed it into ours
so that we can get the most comprehensive worldwide database of
safety. Then, as soon as we have a signal or an issue, we talk
to the health authorities, we vary our licence or we take the
appropriate steps.
Q710 Dr Naysmith: That is all very
commendable. Have you ever suggested to the Government ,in this
country, or the Department of Health,that the system they use
in this country for reporting adverse effects of drugs does not
really work? I am sure Dr Dollow will confirm that the card system,
where a card is supposed to be sent in by GPs and hospital doctors
when they see adverse effects, is widely recognised to be a bit
of a nonsense. Dr Patterson, you would find a lot more adverse
reactions being reported to you if we had a proper system for
doing that.
Dr Patterson: The UK, of course,
represents only about 3% of the sales of our products globally,
so it is a relatively small percentage.
Q711 Dr Naysmith: It would be a statistically
significant cohort if you were studying something about a drug.
Dr Patterson: That is certainly
true. We would always encourage every country to have the right
kind of systems that are as comprehensive as possible. Of course
we do have in the UK the Southampton unit which actually prospectively
goes out and takes cohorts of patients and looks for specific
events. It is not instead of spontaneous reporting but in addition
to it, to get these things put into the context of the wider usage.
These things are not absolute: you have to put them into the context
of the disease and the other medicines that are available.
Q712 Dr Naysmith: Does Dr Dollow
agree with me that the card system, on which medics are supposed
to send in adverse effects, does not work very well?
Dr Dollow: Let me reinforce, first,
John Patterson's view. GSK has a system which is essentially similar,
in that we absolutely report all adverse effects on a global basis
to all authorities worldwide but we can only work with the information
that we glean from our clinical trials and spontaneous reports
and systems such as yellow cards. We again have a large safety
department in the UK and the US and around the world which reports
these adverse events. They are individuals who spend much of their
day trying to get much more information. I think the yellow card
system was a great innovation. I think the difficulty, as people
have previously said, is its expansion: whilst supportedand
we would certainly recommend that any expansion of it be supported,
including patient reportingthe difficulty behind it is
getting the robust information. In one of the previous evidence
sessions, Professor Vallence mentioned the use of the general
practice research database. That is a very good idea and we would
certainly recommend that GPRD is expanded to beyond the cohort
of patients that it currently has. Currently GPRD works by a diagnosis
being put in and the name of a medicine being put in and then
the analysis has to be associated by someone specifically doing
an analysis. We would recommend not only expanding it as part
of National Health Service IT expansion but also people putting
in adverse events and labelling them as adverse events so they
can go further in. So I think the yellow card system is very good
and we support its expansion but I think there is more we can
do. Certainly we would be very welcoming of anything the Committee
recommend to support that.
Q713 Dr Naysmith: We are getting
a bit short of time now, but could I quickly ask GSK about Seroxat
and the fact that, up until quite recently, June 2003, the company
maintained that withdrawal symptoms from Seroxat were very rare,
round about 0.1% was the figure, and now you have to accept that
it is nearly 25%. How did that come about? There is evidence that
you knew before June 2003 that the figure you were using was wrong.
Dr Dollow: I think it is important
to put it in context. I think it is a good example of how labels
change over time: so the labelling, be it in the patient information
or the doctor information. I would confirm also that withdrawal
effects and discontinuation symptoms have always been in the Seroxat
label, so it has always been there both in the patient side and
in the doctor side. It has, however, been updated over time as
more information has become available to us. The fact that more
information becomes available to us allows us to make a reasonable
recommendation based on the data, so that we can say the frequency
of those adverse events and the descriptions used for those adverse
events is more appropriately labelled. Additionally, I think,
when it comes to patient information leaflets, it is a very good
example of how patient information leaflets can be worded more
appropriately. Seroxat is an example where we have extensively
done user testing. Patient information leaflets, while they legally
have to be compatible with a summary of product characteristics,
sometimes are written in a way which is unhelpful to patients.
We have found through the Seroxat process and through extensive
user testing that the patient information leaflet is now more
friendly. I think we would also recommend that more user testing
happen with patients, such that they are written from a blank
sheet of paper whilst still being compliant with the summary of
product characteristics.
Q714 Dr Naysmith: Despite what all
of you have said, does this episode not indicate looking a bit
more closely at some of the harmful effects of drugsand
I know you disagreed with the original question, Dr Pattersonthat
it might be worth spending a bit more resources looking at that
rather than looking at the beneficial effects once you get to
the market?
Dr Dollow: Someone who has a patient
in front of them recognises that any prescribing decision is taken
on the basis of the risks of the disease the patient is suffering
from, the risks of prescribing the medicine and the benefits that
medicine is going to bring. When we think about the evaluation
of our medicines and safety, we have to take it in those contexts.
We cannot separate them. People have recommended, for example,
that safety evaluation be separated within the MHRA. I would,
I think for clarity, recommend to the Committee that it is actually
all within the MHRA but is in separate lines at the moment. We
would support keeping it within the MHRA but ensuring that the
safety and the efficacy are considered together.
Dr Patterson: In terms of the
things that are recognised as potential issues, either from the
trials or from the literature, we do diligently follow those.
I would give you an example. On Crestor which was mentioned earlier,
on a weekly basis now I see a graph of the incidents and a report
every week as to key events that may have happened, number of
deaths, etc, and where that sits opposite the whole literature.
That is worldwide on a weekly basis. Where it is an issue is where
something is totally new; i.e it has not been described before.
There it comes down to pattern recognition, which might come from
a doctor seeing it in several of their patients and often comes
from aggregating together experience over a number of trials for
the development of longstanding trials in the course of the market
place. That will always happen, particularly with the much less
frequent side effects. If something happens one in a thousand,
and you have 3,000 patients in your database or even 30,000 at
the time of launch, unless it is unique, unless the drug turns
your ears green or does something like that, it is unlikely to
be picked out if it is a slight excess of something that the patient
suffers from with that disease anyway, and you need large databases
and long periods of time in order to pick it out. We do look for
pattern recognitionthat is what our SERM process doesbut
it sometimes takes 10 or 12 trials to be published before that
comes together and the signal comes out.
Q715 Mr Burns: The ABPI and its international
equivalents have recently announced the launch of a clinical trials
register. It is going to go further than the voluntary schemes
currently in place. Do both of your companies support the setting
up of a public register of all clinical trials registered at inception?
Would you be happy to see it run by an independent authority?
Dr Dollow: Our company is on record
as going further than the current recommendations, so, yes, we
would support that, both for results and from studies from inception.[16]
Dr Patterson: All clinical trials,
yes.
Q716 Mr Burns: What about run by
an independent authority?
Dr Patterson: I do not think it
matters. A register is a register, as long as the right information
is there and it is only done once. We have a multiplicity of new
registers appearing at the moment.
Q717 Mr Burns: The pharmaceutical
industry has told us how it wishes to work closely with government
and the regulators. If such a relationship is attractive, why
is it apparently that companies from time to time omit to give
all the data at their disposal to the regulators or to NICE?on
the assumption that that statement is true.
Mr Brinsmead: We, as a companyand
it is the same for every companywould have to submit all
of our data to regulatory authorities around the world, so I am
not sure that is true.
Dr Patterson: I think what you
are driving at is the situation where maybe the work has been
done outside the label of licence indication for a product, where
the company is not applying for a licence for that indication.
With a product coming to the market place for the first time,
absolutely everything from everywhere is in there. When a product
is out in the market place, people may use the product in other
countries or of their own volition for things that are not part
of the licenceand they may do that themselves. Once a product
is there, any doctor can buy the product and use it or any hospital
can use it for whatever they wish. We do not control that. If
they then do that, we may not even have that information to provide
it.
Q718 John Austin: I wonder if I could
come back to the question on Seroxat. You said in response to
Dr Naysmith that there was a period when you changed your view
from severe withdrawal symptoms being rare to acknowledging the
real level, but is it right that the initial clinical trial showed
a significantly higher rate of significant withdrawal symptoms
than you were suggesting when you were suggesting they were rare?
Why were you acting so defensively, almost in denial, when members
of Parliament tabled an early-day motion a couple of years ago
regarding the problems of withdrawal from Seroxat when you knew
that there were significant symptoms?
Dr Dollow: First, let me respond
to the point about the level of withdrawal symptoms from one single
clinical trial. That was a control which started putting people
on several levels of Seroxat, so it started with 10, 20, 30, 40,
which did not mirror clinical practice, and stopped them very
abruptly. The levels in that one trial did not reflect the balance
of all the evidence that was available from all the dossier that
was submitted to the regulatory authorities. At the time that
we put the information in our label about the discontinuation
symptoms, that reflected the knowledge that we had and that reflected
the knowledge that was available across the world. With regard
to the evolution, we did not change our label at one point. The
label evolves over a period of time, every time that it is being
revised when there are safety updates and revisions to the licence.
With regard to the early-day motion, I am afraid I do not have
specific information about that, so I would probably have to get
back to you on that.
Q719 Mr Jones: You are multinational
companies operating in the world market and Britain is a very
small part of it. What importance do the changes our government
might make in the way in which they regulate drugs have to you?
Is it more as an example to other governments or is it important
in itself?
Dr Patterson: This is our home
market for us. We have a third of our global research and development
here; we employ some 10,000 people in this country. It matters
enormously to us that this is an environment in which science
is good, in which scientists can work in academic laboratories
or in our laboratories with animals without fear; it matters to
us enormously that the national health system is somewhere where
we can do what is called translational research. We particularly
focus our cancer work in this country and work with people who
can then take those products into the early testing in man in
a very well organised and scientific manner, and it matters to
us at the end of the day that those people who have worked with
the medicines in research are able to use them in the market place
and able to talk to their colleagues globally about their experience
with these products. So it matters.
Mr Gray: I would support that
it matters absolutely. I think I would also add that recommendations
both from the Government and indeed from inquiries like this one
also pertain to the very original questions that the Chairman
was putting with regard to our reputation also. I think, therefore,
we would take them extremely seriously.
Chairman: Could I thank you, gentlemen,
for an excellent session. We are most grateful to you.
16 Note by witness: GSK's position is that
it supports both clinical trials results and studies from inception
being available. All relevant information should be on such a
register, and the register should be accessible. By whom a register
is run seems to GSK largely immaterial. GSK does not rule out
support for an independently run register, but remains unclear
as to what advantage there might be, or are being claimed for
such an arrangement, as compared to the existing position. Back
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