Examination of Witnesses (Questions 940
- 959)
THURSDAY 3 FEBRUARY 2005
LORD WARNER,
DR FELICITY
HARVEY AND
DR JUNE
RAINE
Q940 Mr Jones: Are you saying that
you, as a body, were given all the information that was available
for you to make a reasonable decision at the time you made it?
Dr Raine: Yes.
Q941 Mr Jones: So there was no fault
on your side and no fault on the company's side either then?
Dr Raine: Going back to 1990,
the data were provided according to the guidance operating at
that time to enable a robust decision on risk and benefit in 1990.
Q942 Mr Jones: 1990. What has happened
since?
Dr Raine: Since then, as is normal
for medicines, a vast amount of information is gained about clinical
use, other studies are conducted in other indications and, as
we have stressed, in this case, there was a substantial body of
information available from patients themselves. To make a re-visited
risk benefit judgment, all of that was taken into account.
Q943 Mr Jones: You do not think you
could have improved the situation then at the time?
Dr Raine: In 1990 the product
information reflected the understanding of the balance of risks
and benefits and the advice of the Committee on Safety of Medicines
at that time.
Q944 Mr Jones: May I move on? In
the absence of near certain evidence that the regulators tend
not to issue formal warnings of risk, are you satisfied the regulators
effectively communicate uncertainties of risk to the users?
Lord Warner: The documents the
users get are the patient information leaflets, which are themselves
modified over time; as new evidence comes around people do revise
the patient information leaflet. It is probably the thing on which
patients rely most. If you say to me "Are patient information
leaflets perfect in every way?" the short answer is that
they are not and that is why there is new legislation coming through
Europe to ensure that patient information leaflets are themselves
produced with much more user involvement in their production.
As I recall, I will get my colleagues just to check, that new
legislation comes into operation in October.
Dr Raine: Perhaps I might just
expand on that. The new requirement that medicines information
for patients is tested in the population who are going to be using
that medicine was in fact introduced early, so it will become
operational from 1 July.
Lord Warner: We are trying to
construct a situation in which the document which is the lead
document for patients about particular medicines is framed in
a way which is most useful to patients. I suspect what lies behind
your question is: is it always easy to tell from the document
what the real risk benefit to particular people is? I think that
is a perfectly fair point to be made and that is why we have to
try to improve the quality of the presentation of information
in those leaflets. I think you will find that somewhere in each
of those leaflets the danger signals are signalled. The question
is whether they are signalled in a way which is most helpful or
whether they could be made more helpful to patients on a particular
product. We have already published a leaflet from the new group
that we have set up in this area to try to help patients themselves
understand risk issues.
Q945 Mr Jones: What about information
given to the prescribers? Is it made clear to the prescribers
that this product has this potentially beneficial effect, but
that there is a range of unknowns and possibilities that it may
have?
Lord Warner: Well of course there
is a very vast array of information given to prescribers. There
is a National Prescribing Centre and their various bulletins are
sent to prescribers. The very fact that we have such a high generics
prescribing rate suggests that prescribers are, on the whole,
pretty well-informed about the products.
Q946 Mr Jones: As we have had evidence
before, the access providers get to information about new drugs
comes overwhelmingly from the people who are producing the drugs.
Therefore, it is unlikely that the person who is selling the drug
is going to highlight what potential risks there would be to that
product.
Dr Raine: Perhaps just a word
of clarification. The information that the company provides is
very strictly controlled in law. The terms of the marketing authorisation
include the document called the Summary of Product Characteristics,
which is an evidence-based document on which we seek advice from
the Committee on Safety of Medicines. The controls on any communication
are that they must strictly adhere to those terms. So that is
the starting point for advice to the user or the prescriber which
is an evidence-based document.
Dr Harvey: May I also add that
the National Prescribing Centre does indeed send bulletins to
doctors, not just for drugs which are quite a long time post-licence,
but it often sends out bulletins at the time, or very shortly
after licensing of new drugs, which deal with their clinical and
their cost effectiveness. It also sends bulletins through for
drugs which are on the horizon, which are likely to be coming
to market shortly. So, in fact, prescribers do have information
not just from the pharmaceutical industry, but also from other
independent sources as well.
Q947 Dr Taylor: May I just follow
that up absolutely specifically. To take Vioxx as an example,
on the day of release I am sure there was a lot of material, albeit
controlled, from the makers. What, for example, would an ordinary
GP have had to tell him why to be cautious about Vioxx on the
very day that it was released, remembering that the GP probably
will not look up the BNF every day, will not read the Drug
and Therapeutics Bulletin every day? What would he have had
in practice to compete with the stuff from the drug industries?
Dr Raine: May I describe what
happened on 30 September 2004? It would perhaps Chairman help
the Committee to know that this was a voluntary decision by the
company.
Q948 Dr Taylor: I mean at the moment
of marketing, not at the moment when it was decided to put restrictions
on it. What I am trying to get at is how we could prevent GPs,
who are the bulk of prescribers, going into a new drug with tremendous
enthusiasm right at the beginning when the side-effect profile,
the problems, cannot be known. I think the minister said that
there were thoughts about limiting the numbers of doctors that
could prescribe new drugs. What I am getting at is, what actual
information, other than from the pharmaceutical industry, would
a practicing GP have had about Vioxx on the day that it was liberated
to warn him to be a bit careful and not to use it as the first
choice non-steroidal anti inflammatory drug on a patient?
Lord Warner: It is almost impossible
to answer your very specific question about one particular day,
when Vioxx was put in the public arena. What is a fairer way of
trying to answer your question is to go through all the sources
of advice and information that are actually sent to GPs which
cover all new products. I do not want to sound as though I am
reading out a shopping list, but it is important to realise what
these other sources are. There are 1,200 NHS prescribing advisers,
mainly pharmacists, there are Area Prescribing Committees, there
is the BNF, there is NICE advice on particular products, admittedly
not on the day that you are mentioning, there is the National
Prescribing Centre which sends out MeReC bulletins, newsletters,
there is the monthly Drug and Therapeutics Bulletin published
by the Consumers' Association, there is a vast array of information.
With respect, Dr Taylor, that does cover things like Vioxx very
close to the point when they are being, as you put it, liberated
for the GP.
Q949 Dr Taylor: We do know that GPs
are faced with a vast amount of information. What I am trying
to get at is whether there would be a mechanism for a specific
very brief message of caution, or whatever, when any new drug
which is potentially an advance is liberated, absolutely obligatory
reading somehow to advise caution, so that the things are not
thrown around as freely as Vioxx was?
Lord Warner: I am certainly happy
to look at the issue, but my experience of GPs, and I would certainly
defer to you in this particular area, but my experience of GPs
is that they take their information from sources that they trust
and we do have a black triangle system which does also give alerts
about being cautious in particular areas.
Chairman: May I just make a point? In
a sense I am trespassing on an area which Richard wants to raise
anyway later on. Last week some of us from the Committee went
to meet the Use of Medicines Committee at UCLH and we were actually
very, very impressed by the work that they were doing, but struck
by the fact that a similar mechanism did not exist within primary
care where the industry have direct access probably more often
to the GPs than happened in a hospital environment. There was
not that mechanism for actually looking very carefully at what
was being prescribed and that was an area where we felt there
was a big gap.
Q950 Dr Taylor: Yes, we were incredibly
impressed with the method of control of prescribing at UCH and
the spin-off onto local PCTs. They certainly had controlled the
use of some of these new drugs and we really wondered whether
there could be some standardisation of drug usage committees throughout
the NHS because where you have a very good one, at UCH, it overspills
into the hospital prescribing and the local PCT prescribing and
this would seem to us to be quite as important as things like
ethics committees, which are standardised, and could make a huge
contribution. I think this would perhaps lead to the more rational
use of some of the new drugs as they come out. It is really a
question of the importance of these committees when they really
work and how the government could support these.
Dr Harvey: We do have prescribing
advisers at PCT level, but the area prescribing committees are
very much around looking at the use of drugs across the primary
and secondary care interface and you would expect within those
committees that you would have representation from the various
NHS trusts within that area, as well as the PCTs, to look at the
sort of prescribing habits they have and to look to see what their
general policy across the piece is, so I think part of that is
possibly covered within the area prescribing committees at the
moment. It is actually also fair to say there was a report Primary
Care Prescribing a report for Primary Care Trusts by
the Audit Commission back in 2003 where they looked at some of
the activities that primary care trusts are taking forward around
prescribing. As you said, in many cases GPs directly see pharmaceutical
representatives, but in some PCTs—and they gave an example
of somewhere with a slightly different approach—they actually
went to an information centre where that information was then
distributed. So there are different mechanisms at PCT level, but
the area prescribing committees and indeed the prescribing advisers
are very important in giving help to prescribers within primary
care.
Chairman: It is probably important to
make the point that we did have contact with a GP who was on this
particular committee; although it was hospital based of course
the PCT was represented. The picture we got was very much of a
concern within the hospital environment that patients were being
admitted who had been using products that certainly had been looked
at by the committee and not seen to be particularly helpful for
the condition from which they were suffering. So there was a concern
about direct access to GPs and the impact that was having. That
was the evidence which came over quite strongly.
Q951 Dr Taylor: Another point from
that meeting. They obviously had a very effective formulary and
I do not mean anything like the British National Formulary, I
mean really just a list of the sorts of things that they would
sanction the prescribing of, and it seems to be fairly ridiculous
that every PCT, every trust works on their own formulary. Why
could there not be a much wider-ranging formulary agreed across
many PCTs, across many strategic health authorities and many trusts,
rather than everybody trying to invent their own wheel?
Lord Warner: Of course NICE guidelines
do that, but they are very specific to specific products, are
they not?
Q952 Dr Taylor: They only come in
two years after they are put NICE and there is a very limited
range.
Lord Warner: May I ask Dr Raine
to try to explain the black triangle system, because I think the
black triangle system does actually deal with some of the concerns
that you actually have.
Dr Taylor: Yes, that was explained to
us actually.
Q953 Mr Jones: From the black triangle,
can I move to the yellow card, because I think all the evidence
we have received says that the Yellow Card system does not work.
So, minister, what are you going to do about it?
Lord Warner: All the evidence
I have suggests that the Yellow Card system does work, but could
be improved, so we are probably coming at this from a slightly
different position, if I may put it that way. We did have a review
of the Yellow Card system by Dr Jeremy Metters, which was published
last May and that was looking at several things. Essentially what
he was saying was that, with appropriate safeguards, the information
that was available from the Yellow Card system should be available
to researchers much more easily, so that became a resource there.
I do not think there was any evidence from that inquiry or from
any other work that I have seen that the Yellow Card system did
not feed in as an alert to ensure that the regulator accumulated
information about particular areas causing concern. What it did
identify was, in a sense, a gap in the ability of patients to
be able to fill in their own yellow cards and send in direct to
the regulator, their own perceptions of adverse reactions. I think
there is a misunderstanding to some extent about the Yellow Card
system. Every time you get a yellow card, it is not conclusive
evidence that a particular product is causing a particular reaction
in a particular person. It is saying that a particular person
has had some reaction.
Q954 Mr Jones: I understand that.
Lord Warner: I get a fairly substantial
parliamentary correspondence on the subject of yellow cards.
Q955 Mr Jones: Not from me. I understand
that.
Lord Warner: I think it is important.
I do not think it is always fully understood.
Q956 Mr Jones: Well I think we understand
it, but yes, obviously each individual yellow card does not really
tell you a great deal in itself. Where it becomes useful is if
you have a substantial basis of statistical evidence from a large
number of people who are saying similar things. The reason the
Yellow Card system does not work is that you do not have enough
information coming in from them; you do not have enough yellow
cards being reported to you.
Lord Warner: Volume does not tell
you necessarily to ring the alarm bell. We accept that we need
to change the system so that it is easier for patients to complete
their own yellow cards and make their own notifications and that
is why we have, and I will ask Dr Raine to give you a little more
detail, a pilot which we are now running in this particular area,
which does try to address some of those concerns, certainly in
terms of getting a faster, higher volume, patient response.
Dr Raine: Yes, I would reinforce
what the minister has said. Every adverse reaction does not need
to be reported in order to generate signals. The importance is
to have enough and to have them in time to act quickly. That is
why, over the years, we have expanded the reporting base from
the original doctors and dentists and coroners to include pharmacists
and nurses and now patients. It is the breadth of capture that
we need, plus the facilitation of their input via electronic,
via a number of mechanisms which are currently being piloted as
the minister says. We now have paper reporting, we have reporting
via the internet for patients and as of the 17 January I am very
pleased to say we are up to about 35 reports now from patients
and this is all vitally important in picking up those signals,
but it is only a part of the comprehensive programme of pharmacovigilance
that the MHRA operates. It is the initial trigger for a number
of actions that will strengthen, confirm, or refute the signal
and enable us to take prompt regulatory action and the tough decisions
which need to be taken to protect the public.
Q957 Mr Jones: Did you say you are
up to 35 reports from patients?
Dr Raine: From patients in a matter
of a week or two, yes.
Q958 Dr Naysmith: I want to explore
a little bit what Richard was exploring a minute or two ago, but
from a slightly different angle. We have had a lot of evidence
that GPs can sometimes be a bit profligate in their prescribing
of drugs and that that is probably related to drug companies targeting
GPs in different ways. We have heard evidence too that, increasingly,
nurses are being targeted now that they have prescribing powers.
As you say, there is lots of information about: there are the
black triangles and there are the NICE reports and there is the
Drug and Therapeutics Bulletin and all that sort of thing.
However, in the midst of this comes nice glossy advertising from
drug companies which can be used and busy GPs might think this
is the right thing, this tells them all they need to know. I know
that is not what the best GPs will do, but it certainly does happen
with some and from your answers so far it sounds to me as though
this does not really concern you very much, the role of advertising
coming from the producers in the midst of all this information.
You seem to think that because all the other information is there,
then it does not matter too much that there is this glossy stuff
produced by the drug companies.
Lord Warner: I certainly would
not want to convey the sense that I do not take that point seriously.
I think I was trying to say that there is another side of the
equation which is the volume of other sources of information to
GPs that actually exist.
Q959 Dr Naysmith: My point is that
probably the material coming from drug companies outweighs all
of that information. I know, as Dr Raine told us, there are regulations
about what can be said and it is controlled but . . .
Lord Warner: May I just give you
a couple of statistics which I think slightly call into question
the idea that GPs are sitting there and just simply lapping up
everything which is put to them by a drug company?
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