Examination of Witnesses (Questions 980
- 999)
THURSDAY 3 FEBRUARY 2005
LORD WARNER,
DR FELICITY
HARVEY AND
DR JUNE
RAINE
Q980 Dr Naysmith: One of the things
we were talking about earlier was the question of new drugs and
their efficacy and safety and so on. This is an old chestnut with
this Committee, but we are very much in favour of being able to
look at old drugs as well as new ones, through NICE preferably,
and we have said before that we think it is under-funded and under-resourced
and if it had more money and more resources, then it could answer
some of these questions much more quickly. I should just like
to ask you whether there are any plans to try to encourage NICE
to take on more work, which is what it amounts to basically.
Lord Warner: I am not sure that
the Chairman of NICE would thank me, if I said that they should.
Q981 Dr Naysmith: I think he would
Lord Warner: I think NICE has
been one of the great success stories in terms of the service
that they provided to the NHS and doctors and other health professionals.
We can certainly look very carefully, and we do look very carefully,
at the references to NICE. I think there is a moving pattern really
in which we are putting more guideline references to NICE compared
with single products which is where much of their early work started.
We are trying to get that better balance, so that they look at
total disease conditions—it relates back to some of the
earlier discussion in this Committee—they take the whole
disease condition which a group of people may suffer from and
look at what is the best way of treating that and put in place
within their guideline, the role of the pharmaceutical product,
if there is a pharmaceutical product. That is where we are trying,
with the co-operation of NICE, to take many more of the references,
so you get a more holistic picture of what is the best therapeutic
response to particular sets of disease conditions.
Q982 Dr Naysmith: I remember when
it was set up, that we were really going to look at some of the
old techniques as well and it tends to get dominated by innovative
drug therapies and so on, which is a pity. What you are recommending
now, what NICE is doing now, will be very helpful in that respect.
Lord Warner: Fracture clinics
was a good example, where you are actually looking at the phenomena
which are taking place in the health service and actually balancing
out the drug therapy against the whole range of services or responses
that you need for people with a particular condition. There has
been a very positive response from the NHS at getting that kind
of guidance rather that just guidance about a particular pharmaceutical
product.
Q983 John Austin: Going back to something
you said earlier on when we were talking about mild depression
when you made a comment that NICE now recommends against initial
drug treatment use in the case of mild depression, I know that
follows on as well the expert working group's conclusions that
SSRIs were not effective in the treatment of mild depression.
Although I welcome those conclusions, both of the expert working
group and NICE and the guidance that NICE has given out, why has
the MHRA not advised prescribers of patients of this?
Lord Warner: I am sorry, I am
slightly confused there. The basis of NICE guidance is that that
then becomes the source of authoritative advice to doctors. One
would not expect the MHRA to be communicating that. I am not sure
I fully understand the question.
Q984 John Austin: The MHRA's key
conclusion still remains that SSRIs are effective medicines in
the treatment of depression. There is no added qualification now
that this does not apply in cases of mild depression.
Lord Warner: My recollection is
that guidance went out at the same time, but I do not know. Dr
Raine, would you like to say something?
Dr Raine: Yes; certainly. The
focus of the MHRA work was to review in the context of the safety
concerns, risk and benefit, but the therapeutic advice, which
was issued at the same time, was very much for NICE's remit. The
two are not inconsistent, they should be read together.
Q985 John Austin: You do not feel
the necessity, although you have the opportunity now, to modify
your key conclusion.
Dr Raine: No, I do not think it
needs modifying. It is to be taken in conjunction: the regulatory
risk benefit advice and the NICE guidance on the therapeutic options.
Q986 John Austin: One of the other
issues I want to raise is the implication of licensing of drugs
for particular purposes. The license use of SSRIs for mild depression
led, I am told, to a three-fold increase in prescriptions in the
1990s. Do you have any comments on that?
Lord Warner: I do not have any
particular insights to make on that particular surge in the use
of that particular product. It is not unusual for new products,
particularly when they are thought by doctors to be useful for
their patients, to have a big surge in take-up. One has seen that
in the area of attention deficit drugs as well. What I would say
is that we have tried to balance that with the kind of guidance
that we have given through the NICE process. As I said earlier,
the Audit Commission study that I mentioned of wasteful expenditure
showed a marked decline in the period between the early 1990s
and 2003 in terms of prescribing habits, so we ended up at 2%
rather than 14%. That Audit Commission study suggests that prescribers
are being more cautious than they were in the past about leaping
on band wagons and engaging in wasteful prescribing.
Q987 John Austin: May I come on specifically
to the findings on Seroxat and the expert working group? The working
group learned of the seven cases of suicide in the original clinical
trials, but they appear to have accepted the company's assurance
that none of those cases was linked to adverse drug effects. We
now know that GlaxoSmithKline, or SmithKlineBeecham as it then
was were aware of the potentially serious consequences of withdrawal
symptoms much earlier on, even though they were still maintaining
that such cases were rare, which we now know was a fraudulent
statement. The MHRA and the expert working group do not appear
to have ever examined the raw data; they merely seem to have relied
on the information given by the pharmaceutical companies.
Lord Warner: We went over the
ground earlier about the general points about raw data; I can
go over that again. On the specific issue about whether that particular
company did withhold information—and in a sense it does
not matter whether it was raw data or a summary of the clinical
trials, the same arguments apply to what I am going to say—if
they did in fact withhold information, that would be an illegal
act under the medicines legislation and the MHRA, through their
enforcement arm, are actually investigating the allegations that
have been made in that particular case. That investigation is
not complete. I cannot at this time, as you will understand, make
any further comment on it other than to say if it is found that
there is evidence of non-conformity with the medicines legislation
in providing the information that is required to be provided,
you can take my assurance that there will be vigorous prosecution
in that particular case, if that is the case.
Q988 John Austin: I am grateful for
that. I was somewhat concerned that someone who could have been
a key witness mysteriously could not turn up and give evidence
to us when we wanted to ask certain questions at a previous session.
My question still remains. There was a detailed 18-month inquiry.
If the MHRA does not examine the raw data on suicide cases in
a detailed 18-month inquiry, are we to conclude that the MHRA
rarely does so?
Dr Raine: Perhaps it would be
useful to stress again that in relation to paroxetine we went
back and re-examined the original trials. In that case, the rigour
has extended to that level of detail. If it would help the Committee,
I should be very happy to produce a short note on the precise
methodology which was employed just to clarify that point.
Q989 Chairman: It would be helpful.
Dr Raine: The published document
we now have is some 200 pages long, so a concise note may be helpful.
Q990 John Austin: Were you looking
specifically at anti-depressant safety?
Dr Raine: Selective serotonin
reuptake inhibitor safety; that is correct.
Q991 John Austin: You were not looking
at the wider issues of risk and benefit in that area.
Dr Raine: Certainly the focus
was on the safety concerns. This was the prime reason for the
rigorous review. It had to be taken in the context of this very
serious illness which is a major burden to the public health.
The report itself makes that very clear in one of its first chapters.
Q992 John Austin: May I say that
at the last session the Chairman of the MHRA, Sir Alasdair Breckenridge,
referred to the importance of not discussing the question of drug
safety in isolation and emphasised the need for education of the
public in terms of risk and benefit. I presume that is something
you would agree with.
Lord Warner: Absolutely. I was
very much trying to get that point across in the earlier evidence
I was giving. On the issue of raw data, my understanding is that
in the inquiry on which you have been pressing us, two products,
Epogam and paroxetine were actually subject to very significant
partial re-analysis of data. There was a going back into the raw
data in order to look at some of the issues around suicides and
suicidal indications. In that particular case, the MHRA did not
spend the length of time on just one product, it was a large range
of products; where there was the need they went back into the
raw data to do a re-analysis. It simply is not true that under
no circumstances do they use the raw data: in most cases it is
not necessary to do so.
Q993 Dr Naysmith: It has been suggested
in evidence to us that the post-marketing surveillance function,
checking particularly that licensed drugs are safe, should be
removed from the MHRA just to avoid possible conflicts of interests
arising. What do you think of that?
Lord Warner: My sense is that
this does not happen in other drug regulatory bodies. While I
make a few more remarks, I give my two colleagues time to consider
whether they can think of any other country where that division
has been made. I do not think there has been, from recollection.
Q994 Dr Naysmith: Can you understand
how, from the outside, it looks as though there must be some conflict
of interests when the minister responsible for drug regulation
is also the co-chair of the pharmaceutical industry competitiveness
task force?
Lord Warner: There are two things,
are there not? There is the situation within the regulator and
the situation at the political level with the minister. Within
the regulator, there is operational separation of post-licensing
supervision in the form of Dr Raine and the people who are dealing
with the original licensing applications. It is useful to have
within the overall body both these functions combined, although
there is a clear separation of the staff who are working on those
two particular functions and it only comes together in the chief
executive across the agency. It becomes easier for the post-licensing
scrutiny of a particular product to be carried out if they can
get access easily to the data which was around at the time of
the licensing application itself; that becomes operationally a
simpler thing. I would argue there that there is not much of a
case for separating them up into two bodies with all the overheads
which go with two bodies when there is no evidence, as I recall,
that any other country has gone down that path.
Q995 Dr Naysmith: I think the Netherlands
have, have they not?
Lord Warner: There is some doubt
as to precisely what they have done.
Dr Harvey: I think in the Netherlands
the final decision around pharmacovigilance still sits with the
licensing body.
Dr Raine: Yes; absolutely. Although
they collect ADR reports and do a certain amount of signal detecting
work in a separate body, it is the licensing body equivalent which
does the risk assessment and risk management decision making.
Q996 Dr Naysmith: They definitely
separate pre- and post-marketing functions in the Netherlands.
Dr Raine: It is not directly comparable
in that way. There is a separate collecting of ADRs but not the
decision-making process, which is centrally done.
Lord Warner: So the actual decision
to withdraw is taken by the same people who take the decision
to licence in the first place. I think that is the point my colleagues
are making. In terms of your other point about whether the person
sitting in my job, past, present or future, is able to strike
the right balance, I tried to get the arguments across in my opening
responses to the Chairman's questions. I think a balance can be
struck and I think it is important that we do not get into a situation—the
only point I would emphasise—where preoccupations with short-term
financial issues in relation to healthcare, which is a problem
in many countries and certainly is a phenomenon in some European
countries at the moment, actually dominate the decision-making
in relation to the future development of particular products.
If there is no scope for encouraging the development of research-based
products in this area, the only people to suffer ultimately are
the citizens of that country because you diminish the flow of
new pharmaceutical products onto the market through a research-based
industry. We think that balance has to be struck and under successive
governments we have struck that balance by combining in one department
the responsibility for running the NHS effectively and being the
sponsor organisation for the research-based pharmaceutical industry.
Q997 Chairman: What I think Dr Naysmith
is after, and it is an interesting question, is whether you find,
as co-chair of the competitiveness task force, also with responsibilities
for the regulatory mechanism, that on occasions you have to make
some pretty difficult decisions on which side of the fence you
may need to go. You have an industry which is hugely important
to the economy, employs thousands of people and is a major earner
for Britain, but on the other hand you have that very important
responsibility in terms of public health. Have there not been
situations where you have found yourself in some difficulty in
determining exactly whose side you are on at a particular time?
Issues must have cropped up which have caused you some problems
in that respect.
Lord Warner: I certainly do not
want to give the impression that I am cavalier about this. I do
think about these issues very carefully and I certainly do not
want to give the impression that I am schizophrenic either. What
I think I would say is that if you are trying to achieve a balance
and that is what you are consciously trying to do, you work hard
to achieve that balance. I try to ensure that I hear what the
industry has to say, I sometimes, if I am honest about it, take
what they say with a pinch of salt and I particularly sometimes
take it with a pinch of salt during the course of PPRS negotiations.
I would point to the PPRS negotiations as a good example of where
this balance can be struck. We certainly did not end up in those
negotiations where the industry wanted us to end up and there
was much rhetoric from the industry, if I may remind the Committee,
about a settlement being forced upon them. There were not loud
hosannas in some parts of the industry about the outcome of those
negotiations. Equally, however, at the end of the day, the ABPI
recommended that settlement to their industry. There are difficult
judgments and there is hard bargaining to be done sometimes in
some of these areas. We have touched on some of these issues around
enforcement, when there is poor practice, if you like, in relation
to supplying evidence. Where there is evidence that people have
not supplied the information that they will be required to under
the medicines legislation we will not hesitate to take tough enforcement
action. I believe that it is possible to strike that balance,
but I can see other people might find that the arguments go the
other way.
Q998 Chairman: Cross-dressing in
politics is apparently quite fashionable, but you seem to be in
an impossible cross-dressing position in the role you have. What
I am interested in are your thoughts. What would be the impact
if the commercial aspects, the competitiveness task force aspects
of your role were actually within DTI and the regulatory remained
within Health? Can you see any advantages or can you see any disadvantages?
Obviously that is an issue which, as you appreciate, has been
thrown around throughout our inquiry.
Lord Warner: Once you separate
those two functions it would be far more difficult to get the
right balance. You set up scope for conflict departmentally within
government if you go down that path and I would still cite Europe
in that particular case. Where the going gets rough in public
expenditure terms and you have a slightly embattled health minister
trying to cope with a burgeoning budget against the wishes of
some of his colleagues, this does not of course happen in this
particular country, but overseas there are sometimes less favourable
circumstances that this government has managed to achieve in this
area. Where you get that, there is always the danger that the
short-term consideration, in terms of balancing the health budget,
will over-predominate. That is the argument I would ask you to
dwell on. I would say that can be detrimental to the longer-term
interests of the citizens of that country in terms of the health
products which get developed. There are countries in Europe which
did, 10, 12, 15 years ago, have strong pharmaceutical industries
which have actually weakened very substantially over the last
10 to 15 years.
Q999 Chairman: What you are saying
is that this cross-dressing I referred to is not an impossible
task from your point of view.
Lord Warner: I do not want to
come across as a fervent cross-dresser and I never quite see myself
in those terms, but if that is the label the Committee wish to
apply to me, I am comfortable in that position.
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