Examination of Witnesses (Questions 820
- 839)
THURSDAY 20 JANUARY 2005
PROFESSOR SIR
ALASDAIR BRECKENRIDGE
CBE, PROFESSOR KENT
WOODS AND
DR JUNE
RAINE
Q820 Mr Bradley: Can I take from
that that to date you do not think that your information has been
as good as that put out by the industry and the public are more
likely to take that information and promotion rather than yours,
accepting the point you are making that you will try and do better
in the future?
Professor Sir Alasdair Breckenridge:
Well, we have suffered as an agency for not being professional
enough in our communications. That is the bottom line and we are
determined, as I have said once or twice already, to change that.
It seems strange that a regulatory organisation did not think
that communication was important, but since 2003 it is quite clear,
the importance that it has, and we are acting very greatly on
it. I do not know, Kent, whether you want to add something to
that.
Professor Woods: I would just
add a word because it is a very important area of our business.
We had an independent external review of our communications activities
which reported some months ago earlier last year and, as a consequence
of that, we are forming within the Agency the Communications Division.
That will bring together some 26-27 people, many of whom are already
in the organisation, but we are drawing this together as a focus
of activity. We have appointed a Director of Communications, who
will take up post in about 10 days' time and we are also investing
about £1 million in our website over the next six months,
so this is a very substantial investment, as an organisation,
in our ability to communicate information not only to the general
public, but also to health professionals. We have quite a complex
external environment who require communications from us and I
think that one of the difficulties we have had in the past has
been that because we did not make an explicit task of communicating
in that way, others have done it perhaps with less disinterest
and, therefore, I feel that we do, as regulators, have an important
function in ensuring that we are a source of authoritative, independent
and trusted advice on matters of drug safety, efficacy and quality.
Q821 Mr Bradley: In that review,
did they comment on the fact that your independent review panel
on advertising and on breaches of advertising did not meet at
all in 2002 and has it met since?
Professor Woods: I cannot answer
that specific question. Dr Raine may be able to shed some light
on that.
Dr Raine: You are absolutely right,
it has not met and, for that reason, and it is an appeal mechanism
which industry may choose to follow, we are adopting different
strategies and the main one has been to publish the complaints
that we have. I think you will find on our website that there
are 17 correct statements out there now. It is adopting one of
the successful strategies which the FDA has used which is naming
and shaming. If we cannot get the appeal forum used as a way to
get a rigorous result, then we will adopt other measures and,
as I have said, we are consulting on how we interpret the law
at the moment.
Q822 Chairman: When I opened up,
talking about the changes you are bringing about, one of the issues
which was mentioned was openness and, in particular, your view
that the public should be much more engaged and more aware of
some of the difficulties and some of the implications of the work
you do. I think a theme which has come through our discussions
in this inquiry and, in particular, with the companies themselves
has been their understanding of the need to be much more open
and transparent, but of course at the end of the day in an area
of quite vigorous competition you have got commercial confidentiality
and I wonder whether you feel you can go further on openness and
engagement where you have inevitably at the end of the day got
the problem of this commercial confidentiality. Would you, for
example, like to publish some of the data that you have referred
to which you receive and which currently you cannot? Could we
reach a situation where we could at some point achieve that possibility
which will even more engage with the public and inform the public
possibly?
Professor Sir Alasdair Breckenridge:
Yes, I think, Mr Chairman, there are two changes which are taking
place. Firstly, although we are bound, as you say, by the laws
of commercial confidentiality, if an issue does come up of public
health importance, we will publish that data irrespective of the
commercial confidentiality and we have done this on several occasions.
The second thing which is happening, and I know that you have
discussed this as well, is that there are these proposals which
are going ahead incredibly quickly now about the registration
and the making public of clinical trials, so however these are
worked out, and we are a party to these discussions obviously,
once the public know that a trial has been registered and they
will be able to access the results at some time, it will be impossible
for companies who are starting bits of work to hide that away.
We welcomed this move both to register and to publish clinical
trials and that will make our job much easier, although we still
recognise that there are issues of commercial confidentiality
with which we will have to deal.
Q823 Dr Taylor: Can I go back to
Dr Raine and the problem with the particular drug that I think
Mr Austin raised. Is there a likelihood when patients are used
in market research that this can indirectly sort of turn into
a promotional campaign? Certainly with this particular drug, we
have had evidence that their campaign was actually to target consumers
and patients. Now, are you aware of that? Could you expand on
what you said to Mr Austin before? What methods would you have
of controlling that sort of activity?
Dr Raine: Would you like to name
the medicine?
Q824 Dr Taylor: It is AstraZeneca
and Crestor.
Dr Raine: Yes, of course. No,
our controls on promotion do not extend to the activities and
these would fall under the general controls on clinical trials
and the nature of the consent that needs to be obtained and full
explanation. It would not be within my domain in advertising to
look to see the information that is provided to subjects in trials
of this nature.
Q825 Dr Taylor: So would anybody
be aware of promotional campaigns taken on, which could target
the consumers directly?
Dr Raine: The issue of direct-to-consumer
promotion of a prescription medicine is prohibited very clearly.
The grey area which Professor Breckenridge referred to where we
do have obviously a policeman role is what is called "disease
awareness". Now, the law prevents us from getting involved
so long as specific medicines, specific licensed products are
not mentioned, but clearly, by implication, if there is a new
medicine in a particular area, one can construe that a campaign
might be referring, by implication, to Viagra, for example, if
that is the only medicine in that area. Certainly we would take
very careful advice, including legal advice, if we thought a disease
awareness campaign was effectively promoting a medicine.
Q826 Dr Taylor: Promoting a particular
drug?
Dr Raine: Yes.
Q827 Dr Taylor: So you would be able
to do that?
Dr Raine: Yes.
Professor Sir Alasdair Breckenridge:
Yes.
Q828 Dr Naysmith: Perhaps we can
turn to an area really which you have mentioned already two or
three times, which is this question of balance between safety
and efficacy, and of course we have spent quite a lot of time
talking about safety so far. Could I ask you if it concerns you
that there are pretty reliable figures suggesting that under 50%
of new drugs which get on to the market offer any significant
advance?
Professor Sir Alasdair Breckenridge:
Thank you for asking that question. It is a very interesting question
because when you see a drug being developed, it will be 10 or
12 years before it comes to the market. It is based on a pharmacological
idea and many companies will light on this idea and start to develop
the medicines. Now, the precise route which they go down differs
and the drugs may well come to the market 10 or12 years later
at about the same time and there are several very interesting
examples of where the company, which was first in the field, in
fact did not finish up the best and it was the second in the field
which had a better efficacy profile or fewer dangers. The other
thing which does happen of course is that as drugs are developed,
they very often develop indications for efficacy in areas for
which they were not intended, so whilst the drugs which are developed
down the line from the leaders may not have obvious advantages
in one area, they may well be incredibly important in other areas.
There are many examples of that going back to the 1960s with beta-blockers
and more recently with angiotensin-converting enzyme inhibitors
where it was the second and third drugs in the line where people
began to notice an effect in heart failure and not in hypertension
and these are the mainstays of heart failure treatment now, so
it is a very interesting debate as to what a me-to drug really
means.
Q829 Dr Naysmith: What I am really
interested in is finding out what you can do to encourage less
concentration on need-to drugs. For instance, the FDA in the States
categorise new molecular entity drug applications according to
significant therapeutic advance and what they do with them then
is prioritise them for peer review and moving into the system.
Now, do you operate anything similar to that?
Professor Sir Alasdair Breckenridge:
No, we do not.
Q830 Dr Naysmith: Why not?
Professor Sir Alasdair Breckenridge:
Well, the law says that we will consider a drug for safety, quality
and efficacy. That is the law under which we operate. There are
certain other countries which do, I am aware, operate policies
which you describe, but the European law, as far as I am aware,
under which we operate cannot categorise medicines in that way.
Q831 Dr Naysmith: Are you saying
that it would prohibit you from doing it in that way?
Professor Sir Alasdair Breckenridge:
I think it would. I think that if a submission came to us for
a new chemical entity and its safety, efficacy and quality were
sufficient, we would license it.
Q832 Dr Naysmith: But there is a
backlog, is there not? There is a queue to get things through.
Professor Sir Alasdair Breckenridge:
Well, the queue is much less than it was. You may care to ask
Sir Michael Rawlins in the next session that question because
that is very relevant to his role.
Q833 Dr Naysmith: I realise that,
but it is also relevant to your role.
Professor Sir Alasdair Breckenridge:
Well, with all respect, it is not because we are regulators. We
do not say how people should use drugs and whether the National
Health Service
Q834 Dr Naysmith: So you are criticising
the FDA's policy?
Professor Sir Alasdair Breckenridge:
I am not criticising it. Who am I to criticise the FDA? I am just
saying that they operate under a different legal system than we
do.
Q835 Dr Naysmith: But maybe if we
thought it was a good idea here, we could start beginning to change
the legal system here, if people thought it was a good idea. I
am trying to find out what your views are on it and whether your
Agency, in doing what you do, could be helpful in this.
Professor Sir Alasdair Breckenridge:
For all the reasons I have just discussed with you about looking
into the future as to what the role of an individual agency may
be, I think it would be a very brave thing for an agency to say,
"Look, this is just a me-to drug. We are not going to license
it". I think that is not how I see the role of the Agency.
Q836 Dr Naysmith: I do not think
people are saying that they are not going to license it, but they
are saying that if there is competition for resources, they will
maybe try to go for something which offers more advance potentially.
Professor Woods looks as if he wants to have a go at this one.
Professor Woods: A couple of thoughts
might be helpful. Firstly, the assessment times for new products
have been very substantially shortened over the years and I do
not think there is a queue such that one would need to prioritise
in the way you suggest. The second thing is that although it would
be nice if each innovative drug broke into a new therapeutic territory,
in reality we do not actually fully understand what the utility
of a drug will be at the point it reaches the market. We know
about its safety, its efficacy and its quality to a degree sufficient
to grant the product licence, but its actual utility and use will
become clear. I think the distinction between safety and efficacy
on the one hand and practical utility on the other is an important
one. Speaking as a prescriber, and I spent 30 years prescribing
drugs as a physician, it is certainly valuable to the prescriber
to have a range of options available to suit the needs of the
individual patient. Although you can say that drug A is not as
good as drug B in large trials, when it comes to the individual
patient if drug A does not work, you may want to try drug B and,
therefore, there is that, if you like, redundancy in the system,
but in reality it is the flexibility which allows patients to
be better treated. The other point I would make is that if you
were to consider legislating in a way which inhibited the development
of what seemed like need-to drugs, there is a risk that we would
lose things. For instance, if you take the antibiotic area, there
is a multitude of antibiotics which might treat a particular infection,
but we need all of them because patterns of resistance change
and the likelihood that we might actually discard or obstruct
the development of a drug which five years down the line is actually
the antibiotic that we need because the first four antibiotics
are no longer working, I think that is the kind of practical implication
one would have to think through before considering new legislation.
Q837 Dr Naysmith: Some of the things
you have said are really very interesting because we have had
views expressed here, and I know from my own experience and background
in various aspects of medicine and so on, that we need more, better,
more efficacious new drugs and whilst I accept what you say about
altering the odd molecule here and there can make quite a difference,
there is a concentration, and I am sure many people agree with
this, on diseases which are sort of easy to crack, easy to treat
rather than looking at some of the very difficult ones. For instance,
on a worldwide scale, it is ridiculous that malaria still kills
so many people, but it has been suggested that because there is
not a particularly good market for it in developing countries,
maybe there is not nearly enough concentration. That is a very
extreme example, but the same applies to lots of other drugs,
I think.
Professor Woods: I think that
is absolutely right.
Q838 Dr Naysmith: Witnesses have
told us this.
Professor Woods: Indeed.
Q839 Dr Naysmith: All I am asking
is if there is anything you can do as an agency to sort of encourage
firms to do the right thing. Of course if you are saying you cannot
do it because of legal constraints, then maybe we need to look
at that.
Professor Woods: Well, I think
there are limited things which regulators can do to ameliorate
this situation. It is a problem, I do not dispute that and I think
you are absolutely right, but the drivers which encourage or inhibit
useful innovation in the pharmaceutical area are quite complex
and regulation is only one of them. It can act negatively. If
one creates a climate where innovation generally is made more
risky, more expensive, if one over-regulates, if you like, it
means that the available investment will go towards the safer
products, safer in the commercial sense. To produce another beta-blocker
is not going to be quite as much of a blockbuster as to produce
a completely new treatment for something untreatable, but, on
the other hand, it has a degree of commercial sense about it and,
therefore, it is important to recognise that although regulators
cannot do a great deal to stimulate innovation, and there are
some things we can do which I will come back to, we can certainly
do things to inhibit innovation and we must be careful that we
do not inadvertently do that The ways in which we can simulate
innovation are actually to engage with innovating companies at
an early stage of product development to provide scientific and
regulatory advice, that is to say to help the company understand
the hurdles that will have to be cleared, perhaps a different
mechanism of action, perhaps breaking new ground, to satisfy us
as regulators that it is worthy of a product licence. I think
that scientific advice is something which we have really only
been doing over the last year or two and the number of scientific
advice meetings we hold is going up really quite steeply. I think
that is something very positive that we can do and the only constraining
factors on us really is firstly industry's uptake of that option
which they are very keen to do and the second thing is our resources,
our scientific resources within the Agency, to provide that degree
of assistance. The FDA, to whom you referred, I think have taken
this even further and they have produced a very thought-provoking
document recently called Innovation or Stagnation? which
asks the question and delves more deeply into the matter of, what
can regulators do to foster innovation? The areas they see as
a difficulty are the growth of regulatory science, if you like.
Are there better ways of predicting clinical hazards at an early
stage of development in order that companies do not waste money
on drugs which ultimately are going to fall down? Are there other
surrogate markers which will detect potential hazards at an early
stage and, if so, can the regulators introduce those into the
assessment process? Are there therapeutic markers that we can
pick up earlier in order that the process of development can be
more accurately targeted on those things which are going to work
and have an acceptable safety profile than those things which
are doomed to fail at a late stage of development? Regulators
around the world are thinking about this and both the FDA and
ourselves have discussed it internally at length.
Professor Sir Alasdair Breckenridge:
The other thing is that the picture for malaria, which is an area
in which I am closely involved, may not be as gloomy as you are
saying. There are some very interesting things happening in that
area now, thank goodness.
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