Examination of Witnesses (Questions 659
- 679)
THURSDAY 13 JANUARY 2005
MR EDDIE
GRAY, DR
STUART DOLLOW,
MR CHRIS
BRINSMEAD AND
DR JOHN
PATTERSON
Q659 Chairman: Good morning. Can
I welcome our witnesses and express the Committee's appreciation
for your co-operation with our inquiry and the written evidence
which you have supplied. Can I ask you each briefly to introduce
yourselves.
Dr Dollow: I am Stuart Dollow,
the Medical Director for GlaxoSmithKline in the UK.
Mr Gray: I am Eddie Gray, the
General Manager for GlaxoSmithKline in the UK.
Mr Brinsmead: I am Chris Brinsmead
and I am the General Manager of AstraZeneca in the UK.
Dr Patterson: I am John Patterson
and I am Executive Director of Development for AstraZeneca.
Q660 Chairman: Can I begin by asking
a question, which in a sense is at the heart of this inquiry,
which is achieving the balance between the commercial imperatives
that you people have to work to and the business issues that you
have to address and the wider public health concerns that we have
had put to us during the course of this inquiry. I am sure that
you will probably have looked at some of the evidence that we
have had so far and understand the kind of tensions that we are
addressing: that, from a public health perspective, the concerns
occasionally that the public health interest is not served well;
concerns on the other side that obviously you are a major, a key
player in the UK economy and a very important employer of very
many people. How do we achieve this balance that kind of is at
the heart of the issues we have addressed in this inquiry?
Mr Gray: I think we would agree,
Chairman, that it is a difficult challenge. My instinctive response
would be to say that actually it is a focus upon the patient which
should be the guidance for us all. I think absolutely the approach
that I would hope would come out of an inquiry such as this and
other aspects of health is a recognition that I think healthcare
is a shared challenge. I think it is something in which everybody
has a role to play; we do, not the most important role, but we
do have an important role to play. I have to say that I have been
pleased that there is a kind of acknowledgement throughout the
inquiry you have held so far from many of the witnesses that even
though they may not agree with us on every single point, they
do recognise that there is an important role for the industry
to play. I think clearly there are wider challenges in that issue
of shared health and those which are perhaps most pertinent to
the industry, I think, are to do with the issues of treatment,
but also I think increasingly as society moves on and as we do,
thankfully, conquer some diseases, the issue of preventative health
and how we get that balance right going forward. I think for us
as an organisation we, within that framework, would look at the
whole issue of how do we approach that healthcare challenge where
prescribing is an appropriate response to achieving the appropriate
prescribing in each individual patient's case. I think if, as
a collective in that shared challenge, we can target that and
we can all agree that that is the target and we can build a system
which I think incorporates many of the other threads which have
emerged out of the inquiry, the kind of changing expectations,
which I think we do sense quite strongly around things like public
access, scrutiny, transparency, et cetera, and build that in a
way that ensures that all the people who have a role to play can
be, for want of a better phrase, adults in that environment, then
I think we will be very successful. I think the danger is to think
that if people have issues with the current situation, the conclusion,
therefore, should be to exclude one player going forward in some
way because I do not think that would benefit patients at all.
I think certainly from a GSK point of view, and we have followed
the inquiry very closely, we do have what we believe are some
positive recommendations to add to those we have already submitted
and hopefully at the end, Mr Chairman, you could give us an opportunity
to contribute those.
Q661 Chairman: I am sure you will
want to make those points as we go on with some of the questioning?
Mr Gray: We will try to do so,
yes.
Q662 Chairman: Does anybody from
AstraZeneca want to add to that?
Dr Patterson: I would like both
to echo, Mr Chairman, what Eddie Gray has said, but also to add
one or two things of my own. I am a physician by training. I joined
this industry 30 years ago and the reason that I come to work
every day along with my 60,000 colleagues in AstraZeneca is because
we believe that many of the objectives of public health are shared
by ourselves. In fact we are not working in the opposite direction
in terms of treating disease and preventing disease wherever possible,
so it is the desire actually to find new medicines and improve
public health that makes most of us excited and interested in
coming to work every day. Yes, we do it in a commercial environment,
but that does not necessarily put us at odds with the Government
and there are lots of good examples where the Government's priorities,
the key areas, whether it is coronary heart disease, mental health,
are exactly in line with our priorities for developing new medicines.
Something like just under half of the new medicines introduced
in this country in the last 10 years fit with those key priorities
that the Government has expressed.
Q663 Chairman: So with your medical
background then and your past experience, do you feel that the
balance that I referred to is struck about right at the present
time or should it be shifted in one direction or the other from
your own standpoint?
Dr Patterson: I do not think there
is a balance at the moment. I think in the last two or three years
things seem to have gone completely out of balance in terms of
public perceptions, in terms of people taking some seemingly very
polarised stances in these areas, so I think it is useful to have
a discussion about where the balance should stand. We are going
through a period of dramatic change, a dramatic desire from patients
and the public for more openness than there has been previously,
a desire for perhaps the risk:benefit ratios to be different from
how they have been perceived previously, and I think it is time
to have an open dialogue about those kind of things and see how
we can work together going forward.
Mr Gray: I would just support
that point. I was particularly struck in one of the previous hearings
that you had when there was a phrase, I think, from Sir Ian Chalmers
who was talking at the time about access to clinical trial information,
which I think is what he was talking about at the time. He talked
about the current situation not being consistent with 21st Century
public values. I think within the industry I support John's comments
and I think there is a feeling that actually the expectations
have shifted quite quickly and quite significantly and to some
degree trying to catch a train that is already moving is the kind
of experience that most people would feel some commonality with.
Q664 Mr Jones: I was going to raise
this later, but, Dr Patterson, you just spoke about the balance
having moved very rapidly in the last couple of years. Could you
reflect on why there has been that change and why it is not a
change which is peculiar to the attitudes that people have of
the pharmaceutical industry in this country? I note from a poll
conducted in America that confidence in the industry and the public
perception that the industry is doing a good job has fallen from
79% of the public in 1997 to 44% of the public now, a huge change
in a very short period of time and the conditions in the United
States would seem to be very different from the conditions in
this country, so why?
Dr Patterson: I do not know that
I have all the answers, but I can try and give you my own perception.
I think health has become a much, much greater topic in the media
than we have ever had previously. Every time you turn on the television
or the radio, even the major news programmes are covering significant
health issues, so it has become a much more public topic than
ever previously. There is a tendency of course to polarise and
things are either, certainly from our perspective, wonder cures
or killer medicine and there is very little seemingly in the middle.
Therefore, every time something happens in our world, a new medicine
is introduced, there is a huge media outburst, shall I say, associated
with it and, equally, when something happens with one of our medicines,
that is also very much more public than it ever used to be. One
of the issues that we face is that as we bring very effective,
modern, potent new medicines to the marketplace, inevitably we
are starting to see more evidence of issues of tolerability and
side-effects. It is certainly true that as you innovate, you do
not always know from either the laboratory work or from the clinical
trials exactly what the profile of the medicine is and we have
had a number of high-profile failures as an industry over the
course of the last few years which have been very, very visible
in the public domain, particularly as they got picked up often
early in their life and perceived as being the next panacea, if
you like. There is a more rapid rise and a more rapid fall going
on than we have ever seen previously and these issues have been
debated and people are not well versed, as we know, in many fields
in talking about relative risk, so when there is an issue with
tolerability of a product, to try and put it in the context of
how many people are dying of that disease and what the current
problems of that disease are does not always fit well with the
20-second soundbite on television.
Q665 Chairman: What you are saying
then, Dr Patterson, in a sense is that perhaps the increased media
awareness of, and interest in, health has a bearing on your industry's
image. I was going to move on to one or two comments that we have
picked up on perceptions of the industry's standing. There was
somebody from Mr Gray's company who was quoted in a conference
recently who likened the industry's standing to that of big oil
or big tobacco firms, and I think you may recall that reference.
Richard Sykes said to our Committee when he gave evidence that
the industry is getting, "a very bad name, possibly because
of its competitive nature". Now, the impression that Dr Patterson
is giving us is that perhaps this is an unfair image and these
comments arise very much because of the media's focus on health,
but is there some justification for this image and one of the
reasons for the image that appears to be one that is fairly widespread?
Mr Gray: I think John makes a
valid point about the publicity and the impact that has and I
think he does make an extremely good point around the concepts
of risk and benefit. If I can simplistically put the position,
society's attitude is, "This is a complex area. We'll let
the scientists sort it out", and increasingly as society
has found that to be unacceptable and started to want to peer
in the box and scrutinise, then some of these issues have come
to the fore and at the moment I think that the kind of science
view of risk:benefit and the public view of risk:benefit is a
very different one. I think there is a lack of understanding and
I think it is natural human nature, when you do not understand,
to be suspicious and, therefore, to mark things down.[14]
Q666 Chairman: So to pick up that
point and your point earlier on about engaging with the patients,
what you are implying is that people need to understand more about
the industry, but I would come back and say that perhaps the industry
needs to be more transparent, so how could it become more transparent
and more engaged with the people it serves?
Mr Gray: I think in terms of what
I was trying to say earlier about a kind of moving train and trying
to catch that, I do not think I would argue about that as a direction.
I think it is how we balance that movement against the fact that
the situation is not any less complex than it was, so we are having
to do that in an area that remains. It is still science and it
is still the balance of risk and benefit that has to be assessed,
but I do not think I would argue with that. I think a positive
thing is that having realised that that train is on the move,
we have started to respond, so I think the most obvious example
of that would be the clinical trial registers, et cetera, and
it is a little disappointing that that then gets reported as some
kind of PR exercise when I actually think it is a genuine attempt
to respond to this kind of new expectation and agenda. I think
as a broad principle, how do we move forward, improving the kind
of transparency and scrutiny, but doing it in a way where actually
we can still arrive at good public health patient-centred risk:benefit
balances absolutely is the broad challenge and doing it in a way
which allows the industry to be an adult in that and play its
role, not that the only way is to exclude it in some way or fence
it off, I think that is the challenge, I would agree.
Q667 Dr Taylor: Can we move on to
information and the promotion side. The industry has got codes
and standards that relate to the control of the quality of drug
promotion. Are there any controls on the quantity of drug promotion?
Witnesses have told us in other sessions that whereas research
staff in companies are only increasing very slowly, marketing
staff are increasing extremely rapidly. Have you any comments
on that? Are there any controls on the actual quantity of promotional
material you can use?
Mr Brinsmead: I think the first
thing to say is that if they are talking about the number of people
employed in research and development and marketing, in our company,
broadly speaking, those numbers have remained broadly consistent
over the last sort of five to 10 years, so I am not sure that
would be true for AstraZeneca. In answer to your question around
the amount of promotion, the quantity as opposed to the quality,
there are limits on that both in the code and in companies, so,
for example, the number of times that we can visit a general practitioner
in a year is prescribed by the code, so we do not have any limits,
as far as I am aware, on the amount of material that we may provide,
and the material provided would obviously be down to what material
you need to provide to explain the disease and some of the ways
that the product works.
Q668 Dr Taylor: So the number of
visits to a particular general practitioner is limited, is it?
Mr Brinsmead: Yes, it is, by the
code of practice.
Q669 Dr Taylor: And the amount of
money that the representative can spend on hospitality, is that
limited too?
Mr Brinsmead: I think, talking
about the question of hospitality, we would only provide any hospitality
if it was in association with a scientific or an educational meeting,
so to give an example, it may be that a sales representative would
have a meeting with some GPs at lunchtime and in the case of our
own company, we would limit them to spending no more than £10
on the sandwiches and drinks that they would provide at that meeting
for the GPs, so yes, there is a limit, but I would make the point
that hospitality is really just secondary. The purpose of the
meeting is to talk about the medicine and how it might be used.
Q670 Dr Taylor: Any other comments?
Dr Dollow: Maybe I could give
a bit of context about the development process because I again
would echo Mr Brinsmead's comments that the number of medicines
in development in GSK has increased rather than decreased, so
the R&D expenditure we expect to have increased, so although
I do not have exact figures, I do have figures on the number of
medicines in the pipeline which has increased since the time of
the start of GSK. At the moment GSK spends 40% of its R&D
in the UK, about £1 billion, and 6,000 employees are working
in R&D in the UK. Additionally, we recognise that many of
the products which are coming through in our pipeline actually
have a very high attrition rate, so only one in 10,000 of the
compounds that are synthesised will get to the marketplace to
be medicine and only one in 10 that gets into man will be a medicine,
and I think that is an important one to remember as well.
Q671 Dr Taylor: So that is your firm6,000
in R&D?
Dr Dollow: That is correct, yes,
in the UK.[15]
Q672 Dr Taylor: How many in marketing?
Mr Gray: In marketing, maybe about
120 or something like that, 120 or 130. There is one other point,
if I may, or viewpoint of this which I think is worth thinking
about and that is to kind of put the position of activity and
promotion within the context of what actually seems to be happening
within the UK as a health service and if I look across that big
picture, then I see the rate of generic prescribing at 78% and
a target of 85, and I see the uptake of new medicines generally
being one of the slowest in western Europe, and acknowledged by
everybody as being the case. The last time I appeared before this
Committee it was about NICE and one of the recommendations was
about implementation because NICE was making recommendations,
so here it is effective and safe and it is cost-effective to the
National Health Service and we still cannot get it taken up, so
the broad picture would not suggest that the level of promotion
is bracing things away in any one direction. The big picture tends
to suggest that the checks and balances are working pretty well.
Q673 Dr Taylor: Is it because we
in this country are slightly more cautious than other places?
Mr Gray: Well, I would take your
advice, as a medic, on that!
Q674 Dr Taylor: Witnesses in previous
sessions have suggested that some drug firms are guilty of having
a drug and actually looking for an illness, an extra illness for
it to work on. Are there any comments on that?
Dr Dollow: Maybe I could respond
to that. For any medicine to be approved, it has to be treating
a valid condition, so any condition that we seek to investigate
has to be a condition that is recognised internationally, otherwise
the regulators will not approve it. I do not recognise the fact
that people are suggesting that we are inventing diseases. That
is not something that we would do. Any medicine that we have which
has an indication is certainly related to an indication which
is well recognised by the medical community.
Q675 Dr Taylor: We have got here
two of the largest and, hopefully, most reputable firms. Do you
think any of the other ones are trying to popularise an illness
among people so that one of their drugs would be used more? That
is the sort of thing people have suggested to us.
Dr Patterson: Can I come in on
top of what Stuart said. There is, first of all, a licence and
anything that any company sells has to be within its licence,
otherwise it is breaking the law, and those licences are given
for specific diseases which are usually within what is called
"ICD", the International Classification of Diseases,
so they have to exist to get a licence. Now, it is certainly true
that in order to make it more acceptable sometimes for patients
to talk about their disease, we may give them a nicer name as
an industry, and I will give you an example. No male around this
table, I am sure, wants to say, "I've got impotence",
but by calling it "erectile dysfunction", it has become
a little bit more acceptable, but we did not invent erectile dysfunction;
impotence has been there for centuries and is a considerable issue
for many people. It is maybe part of the semantics of giving it
a nicer name, but you cannot invent a disease against which you
promote a medicine in this country because we have licences.
Mr Gray: I think in watching all
the tapes of the earlier hearings, this is perhaps the kind of
thread of questions which has actually left me most confused,
if I am honest, and I think that there has been a degree of confusion
as to what are the kind of accusations, so to speak. I think this
one about inventing diseases has been answered and I will not
touch on that, but the other one has been this idea that it is
the industry or certain members of the industry in some way trying
to kind of expand the criteria by which patients gain inclusion.
I think clearly there are separate conditions, if I look at the
ones that we are involved in, where the symptomatology is clear
and either you have this disease or you do not or there are well-established
tests for asthma, et cetera, to test lung function, et cetera.
I think the other thing which is changing a lot now which again
is important is that the National Health Service itself, either
through national service frameworks or through the GP contract,
is actually setting the target and the standards which apply,
so if I think about Type 2 diabetes, for example, within the GP
contract they are targeted to have all Type 2 diabetes patients
at 7.4%, so there is absolutely no credibility whatsoever in me
going out and arguing that it should be 5%, so I think there is
again in the way in which individual disease comes forward to
a doctor, supported now by things like NICE guidelines, NSFs and
GP contracts, et cetera, clearer definitions than there
have ever been as to what constitutes an individual condition.
Q676 Dr Taylor: Can you give us any
idea of when a major drug is invented and discovered for one particular
illness and quite legitimately it is discovered that it has actions
on other things? I am thinking particularly of the hypotensives
that were discovered to work well for prostatic hypertrophy. Have
you got any idea of the sort of proportion of money your firms
make from the big blockbuster discovery as opposed to the sort
of creeping growth on to the other indications?
Dr Patterson: Perhaps I can try
and answer that, not quite in the terms you put it. Most medicines
get into the marketplace for a licence in a single indication.
We then continue to work with that product throughout its life
cycle, often looking at new indications, new formulations, new
ways in which it can be of value to patients. It is quite common
for medicines to be used ultimately more in an indication that
was developed later on. An example would be the angiotensin-converting
enzyme, the ACE inhibitors, which started off as anti-hypertensives
and then went into heart failure where they are used fairly uniquely
and are successful. Our job is to continue to do that and, for
instance, this year on a global basis AstraZeneca will spend about
40% of its total clinical development budget on actual life-cycle
management of products that are in the marketplace, so it is very
common for us then to look at the indications and we have to do
that into special groups who are not indicated in the first licence.
There were papers, I think, in The Lancet at the end of
the 1990s which showed that something like half of the top 20
medicines in the world are actually being used more for indications
that came after they had been put in the marketplace than their
first indication, so it is an ongoing process. We live with these
products for the whole of their life cycle to the point where
they go off patent and disappear or are superseded.
Q677 John Austin: I was tempted to
ask Mr Gray if there is any empirical evidence that watching tapes
of proceedings of this Committee might be a cure for insomnia!
My real question is directed to Mr Brinsmead because in your marketing
campaign for Crestor entitled "Right First Time", you
mention the desire to exploit the emotions of prescribers. I wonder
if you could explain that and perhaps describe other means of
stimulating the use of your products.
Mr Brinsmead: Perhaps I can just
take a step back and say that heart disease and problems like
that are a government priority and clearly having a high level
of lipids is something that the Government and doctors and patients
want to reduce because you can prevent heart attacks and strokes,
so we are very proud that we have a statin called Rosuvastatin,
which we brought to market a couple of years ago that does this
more effectively than the statins that are already in the marketplace.
Now, if you think about why people make a prescribing decision,
well, they will make a decision on a rational basis and they will
think about the data, they will think about the patient in front
of them and what this patients needs to do. However, doctors are
also human beings like anybody else and they have feelings and
needs and what we find in the emotional sense is that it is important
that we understand how people feel so that we can actually make
sure that the messages we give them are appropriate. If I gave
you an example, if someone was saying that they were feeling a
bit cautious, a bit uncertain, and we talked earlier on about
whether English doctors were perhaps more cautious than their
counterparts in other countries, then it is important that we
make sure we provide all the tolerability data and the safety
data to try and address that feeling. I think the emotional aspect
of the marketing is particularly important.
Dr Patterson: I think there is
an emotional reaction in this country against using new medicines.
The Government's own figures show that in things like coronary
heart disease, only a small percentage of the patients who should
be receiving those kinds of medicines are doing so, so you have
to look at what it is that is part of the decision-making of that
doctor and appeal to the relevant senses.
Q678 John Austin: I can understand
the desire of companies to get new drugs on to the market fast,
but I think from something Dr Patterson said earlier, should we
not be concerned about the intensive promotion of new drugs which
typically follow the launch of a new product when we are not really
sure of the side-effects or long-term effects of the use of that
drug?
Dr Patterson: I think all new
medicines carry potential risk because new medicines are effective
and they hit pharmacological systems, some of which we do not
fully understand. I think it is very important though that we,
as an industry, who have spent the last 10 or 11 years developing
those medicines, are the people who can carry that information
in to the doctors and allow them to make an informed decision
as to how that new medicine might fit into their therapeutic armamentarium
compared with something they have been using previously. The issue
that you raise is the intensity with which we do that and I am
not sure on what basis we are saying that we are any more intense
than we used to be in that activity. I think we often have more
data, so if you take the medicine we are talking about here, whereas
when I first started working in this industry at the most 1,000
patients would be treated prior to a licence, while with Crestor
we had something like 30,000 patients treated in clinical trials
before we came to the licence, so we knew a lot more about it
than we did with medicines coming in 10 years ago, so there is
a lot of data and a lot of information to be shared, all of which
did not exist in the textbooks when those doctors were trained
and none of which are pieces of information that they will have
seen previously or the people whom they work with in hospitals
will have seen previously, so we have to carry that information
and that requires some kind of a process for getting that message
across.
Mr Brinsmead: Sadly, in this country
only about half of the people who should be treated and achieved
the levels that the Government's targets stated, only about half
of the people treated reach those targets, so there is a positive
outcome of intensely promoting a new medicine and that is if you
can actually prevent more people having heart attacks and strokes,
that must be a good thing. The other thing I would like to say
is that there is the Black Triangle system in this country whereby
all new medicines have a black triangle and that is an indication
to the healthcare professionals that if they see any side-effects,
they must be reported to the regulatory authorities, so there
are ways with a new medicine where the safety of the patients
and the safety of that particular medicine are picked up through
that system.
Dr Patterson: And the data show
that Britain is still the slowest to take up new medicines in
Europe. We take up new medicines at about the same rate as Croatia,
so again we may be being intense in your eyes, but the reality
is that the speed of uptake of new medicines in this country is
slow.
Q679 John Austin: Could I go back
to the issue of Crestor. In July 2004 you developed a PR campaign
to reinforce the positive risk:benefit profile of Crestor when
a month earlier, in June, the MHRA had issued new prescribing
advice for the 40mg dose and a revised pack insert had been introduced
presumably because there was more awareness of risk. Why, a month
after that was identified by the MHRA, did you have a positive
PR campaign to reinforce the positive risk:benefit?
Mr Brinsmead: Well, let me talk
a little bit about that. I think the fact is that as we launched
Crestor and as we got more experience in the marketplace, it became
clear to us that the drug was not always being used appropriately
at the correct start dose and we actually had a series of campaigns,
not just the PR campaign that you refer to, but also we worked
very closely with our sales team and very successfully to make
sure that the drug was used at the correct start dose. I do not
think that there is any negative implication of having a PR campaign
aligned with a change to the prescribing information of the MHRA.
I think it is important that we, as a company, when we get the
information on the drug when there is a change, we make sure that
we tell people about that very, very quickly.
Dr Patterson: We are actually
very proud of that campaign because the start dose for Crestor
has always been 10mg in this country and quite a significant number
of patients, who are often patients who are having side-effects
from other statins or failing to get control, were being put on
by doctors at higher doses than 10mg, so exactly in line with
the agreement with the MHRA, we actually went out with that campaign
and made sure that people started at 10mg and we have reduced
the percentage of patients on the higher doses in this country
by a significant number, and we can show you the data, as a result
of that campaign. PR is not always bad, sell, sell, sell, but
PR can actually be about the proper use of the product in the
right circumstances for better patient safety.
14 Note by witness: "mark down" is
used in this context to mean to view negatively, rather than simply
to take note of. Back
15
Note by witness: The figure of 120-130 refers to GSK's
UK Operations, ie those involved in marketing to the NHS. Back
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