Examination of Witnesses (Questions 20
- 39)
THURSDAY 9 SEPTEMBER 2004
DR FELICITY
HARVEY, DR
JIM SMITH,
PROFESSOR SALLY
DAVIES, PROFESSOR
KENT WOODS
Q20 Dr Taylor: I had rather sensed
the words were being used loosely rather than absolutely accurately.
Dr Harvey: We describe it as top-selling,
but I would have to look at exactly what has been said by the
ABPI there. I do not think there is any particular difference.
Q21 Dr Taylor: I would echo Professor
Woods' comments about the developments. I have been around a little
bit longer, and the developments have been absolutely amazing.
One thing that puzzles me is, when a drug is about to run out
of patent the industry can make a very small change to it or add
a well-known other drug to it, and then market it again as another
patent drug. Is that well-regulated? Are there controls over that
sort of thing?
Professor Woods: If a new drug
is developed, even if a small incremental change to structure
or minor chemical variation to structure is made, then it would
go through the licensing process in the usual way. Of course,
at the end of the patent period for the parent compound, there
would be the development of generic drugs, which would introduce
a very brisk element of price competition in that area. The scope
for extending patent protection by very minor chemical modification
is counterbalanced by the opportunity for generic manufacturers
to come in with the same product, and price competition is developed.
Dr Harvey: As the Committee is
probably aware, we have very much a policy for use of innovative
medicines, where they have been developed, but when prescribed
are done so generically. That has been a fundamental base in the
UK and part and parcel of undergraduate training. As a result
of that, we now have generic prescribing rates of about 78%. In
fact, in some, their generic prescribing rates are as high as
85%. That means clearly that when a drug has come out of patent,
then the drug that is dispensed is a generic of that particular
medicine; and that is very important for us. We have the highest
generic prescribing rates in the whole of Europe.
Q22 Dr Taylor: Dr Darnbrough implied
that the Government was perfectly happy for drug firms to go down
their own path for research. Is that absolutely so?
Dr Darnbrough: I was looking at
it from the Department of Trade and Industry's point of view.
You have heard several statements from Dr Harvey and others about
the increasing discussions between the Department of Health and
the companies to talk about what are the actual healthcare priorities
for the nation and the patients in the UK.
Q23 Dr Taylor: So we have a difference,
from your point of view, behind industry. The strongest motive
is profit. The Department of Health has to have another priority.
Dr Darnbrough: I cannot speak
for the industry, and I think you will have to explore this with
the companies themselves of course. The dialogue the Government
has is a joined-up one, and there are many things that colleagues
in the Department of Health and others in the DTI talk about with
the companies, including, very importantly, what the healthcare
priorities are for people in this country.
Dr Harvey: It might be worth Professor
Davies adding a bit from the R&D perspective. Obviously, the
stakeholder relationship means there is huge awareness of priority
areas within the R&D arena.
Dr Naysmith: We are planning to look
at research later on, so will leave that for the moment.
Q24 Mrs Calton: Can we turn to the
regulation and the trials, particularly as it applies to patients
involved in those trials and the regulatory framework for that.
I understand that the good clinical practice that is followed
has a confidentiality requirement set out by the ICH, the International
Committee of Harmonisation; but it does not permit the regulators
to see the full good clinical practice audit. Can that be right?
Is that satisfactory?
Professor Woods: Since the European
Clinical Trials Directive was transposed into UK law, and taking
effect from the beginning of May this year, inspection of good
clinical practice is a new regulatory role which we have taken
on, which gives us as an agency the opportunity to examine the
operation of the clinical trial at ground level and to also ensure
that any adverse events that occur are reported to us and recorded
rapidly, and from sites which may not be in the UK. The clinical
trials regulations now give added security in terms of the protection
of GCP within the research environment, which were not there before.
The clinical research trials community is very mixed. A large
part of it is pharmaceutically driven and organised, but there
is a large clinical trials activity which is funded by public
sector funders—the major charities, the DoH, the NHS. Therefore,
these trials researchers are working in slightly different communities.
One of the advantages of the new regulations is that it will allow
us to develop consistent standards of good clinical practice across
all trials. Indeed the Department of Health R&D division has
led the way in developing a research governance framework to ensure
that the standards of patient protection and data quality are
consistent and are observed.
Q25 Mrs Calton: Does that mean that
patients are fully protected; if the regulators cannot see the
information and see the audit and the results of the audit, but
do not see what goes into that?
Professor Woods: I would expect
that to be part of our inspection function, to monitor and to
supervise the standards of GCP being conducted in that trial.
Q26 Mrs Calton: Evidence that comes
from Professor Iain Chalmers mentions that the pharmaceutical
industry has a perverse influence on clinical agendas, particularly
with reference to expenditure on drug research, and it is unlikely
to significantly improve public health. Does the Department see
this as an issue?
Professor Woods: It goes back
to the earlier discussion we had about how one can shape the innovation
agenda. Who sets that agenda? Essentially, the influences that
we have on it are limited, but they are definitely there. Of course,
in most industrial contexts a demanding customer helps to influence
product innovation. We have to recognise that there are two separate
issues here. One is the freedom of the industry to explore and
develop areas which it has not been into before, and the other
is the customer's ability to make judgments about the utility
of what is produced. If, incrementally, this is not an addition
to what is there already, it will not be bought and therefore
there will be less commercial incentive to go down that sort of
route.
Q27 Dr Naysmith: Professor Davies,
does the Department have a view, when it says, "there is
an area where we need some clinical research done, but the drug
firms are not interested in it because there may not be much in
the way of profit"? Do we have a mechanism for saying "in
this particular disease we need something where research is not
being done by pharmaceutical companies?" Do we do that?
Professor Davies: We do; we have
our own R&D programme. It does not really fund drug development,
though in partnership we have assisted. There are grades of influence:
as a customer because of need; as a customer because we expressed
an area through the national service frameworks—
Q28 Dr Naysmith: Can you give an
example where that has resulted in a treatment that probably later
became commercially available but would not have done we had not
intervened?
Professor Davies: You have in
your submission from us explanation of the research for patient
benefit working party, which was set up by the Government as a
response to a number of reports, including the Bioscience Innovation
and Growth team and the Academy of Medical Sciences. In the process
of working through what this working party, chaired by my predecessor
Sir John Patterson should do, the drug companies, the pharma companies,
supplied us in confidence with drugs in their pipelines. We said,
and expressed to them, what we saw of areas of great need, and
where there were shared interests for future research. That exposition
they said they found very helpful in guiding them for the future.
We have yet to see how it plays out, but it was in confidence
a list of areas that they were in, and they were moving forward,
and our response to it. There are a number of mechanisms. I have
been approached for instance by a biotech company that has a vaccine
against smoking. Clearly, this is a major public health area.
The venture capital market is not very good, so they are now talking
to Cancer Research UK. If, between them, they can come up with
a protocol that is of high quality, which addresses the research
governance issues that we lay down—and Cancer Research UK
always work to that level—then we will look at partnership
funding in the light of a commercial contract negotiated by a
commercial department, to make sure that developments like that
happen. We are exploring one at the moment.
Dr Naysmith: We have to find another
word than "vaccine" against smoking.
Q29 Mrs Calton: In your memorandum
you state this: "Regulation and guidance is necessary to
safeguard the dignity, rights, safety and well-being of patients
and other participants", and obviously we would agree with
that. You add: "The individual's interests will come first
if they consent to take part in medical research." Should
the maintenance of the rights and dignity of the patient not include
being properly informed about to what use that information, which
has come from their bodies, will be put? It could, for example,
not necessarily be published for the public benefit but actually
end up as marketing information instead. Is it right that patients
do not know that?
Professor Davies: I will pick
up on this as it comes under the area of research governance.
It is for the ethics committees to take a view, and now under
the EU regulation it is a single view for the UK as to whether
the patient information leaflet is satisfactory. But it is quite
clear in their training that they should consider making sure
that patients are aware whether this is a public sector trial,
a contract, pivotal licensing study, whether it is being done
through the NHS or in a private capacity where the NHS is not
involved. The patient information leaflets should give adequate
information, and it is for the ethics committees, which are independent,
to make a judgment.
Q30 Mrs Calton: Do you think it is
happening already?
Professor Davies: I do not think
it was perfect in the past. As a result of a massive amount of
training and education, set up and organised by the Central Office
of Research Ethics Committee, there has been a dramatic improvement.
Q31 Mrs Calton: How recently would
you say that has been taking place?
Professor Davies: Over the last
12-18 months it has really improved.
Q32 Dr Taylor: Are there any figures
for how rapidly ethics committees work and produce results? One
gets the feeling that there is so much red tape now involved before
you can get on to a worthwhile project, that perhaps some are
being delayed and taken elsewhere altogether?
Professor Davies: In the past
every ethics committee could do what they wanted, but with the
laying of the regulations and from May this year, we have bound
all ethics committees to the time line given to us under Article
6 of the EU Directive of 60 days. They are keeping to that and
doing very well, but it is a struggle.
Q33 Dr Taylor: Are research organisations,
whether drugs firms or the NHS happy with that?
Professor Davies: The drug firms
would like to be lower than that, and many are. Some of them are
turning it round in a matter of a week or two, but that will take
time. The bureaucracy has simplified in that we now have a single
form across the country. It is available across the Web. While
it superficially appears complex, speaking as a researcher who
is also applying for ethics committee application, it works that
you can move from one part to another, and it is not as awful
as it looks. But the great advantage of a single form is that
then it is the same form whether you are applying in the north
of England, the west of England or the south of England.
Q34 Dr Naysmith: Can we find a way
to make it not look awful?
Professor Davies: COREC has been
collecting views and comments and will review the form to try
and hep make it more apparently user-friendly. It really is not
bad in practice.
Dr Naysmith: Once you have done a few,
it is easy.
Q35 Jim Dowd: Are you saying that
the amount of medical research that is funded by the taxpayer
through the MRC and academic institutions, universities et
cetera, would only exceptionally look at pharmaceuticals?
Professor Davies: I made no comment
on that. The Government funds using taxpayers' money research
through the Department of Education and Skills, the Higher Education
Funding Council, into universities. That is biomedical and clinical.
We provide, through the Department of Health, support funding
of nearly 600 million to trusts and our national R&D programmes,
including £497 million to trusts. A certain amount of that
does relate to drugs. Much of it is off-licensed, being trialled
for off-licence indications, different indications or comparisons.
I was only yesterday looking at a trial for men with sickle cell
disease, where 50% develop priapism, which is a prolonged painful
erection. There is a treatment that looks to be effective, but
as it can come and go it is quite difficult to know whether the
treatment is working. The drug companies are not interested in
this small market, so we are looking at how we can do a proper
randomised controlled placebo trial in order to judge whether
this is effective. That is in the NHS and the NHS funding.
Q36 Jim Dowd: So the answer is "yes".
Professor Davies: A certain amount
of drug research is undertaken, yes.
Q37 Siobhain McDonagh: Under current
regulations, healthy individuals are entered into clinical trials
before carcinogenic testing involving rodents is complete. Does
the situation protect the dignity, rights, safety and well-being
of patients and other participants?
Professor Woods: Now that every
clinical trial requires a clinical trials authorisation it is
necessary for the proposer of the research to present a persuasive
case that what is being proposed is in scientific terms adequately
safe for the recipients. It is certainly the case that a great
deal of pre-clinical research underpins the first use in man.
There may be some aspects of the laboratory evaluation which are
running in parallel with very early exposures in man, but, as
I say—
Q38 Siobhain McDonagh: Do the same
rules apply to women?
Professor Woods: Yes, okay—persons.
There is this scrutiny at the point of assessment for a clinical
trials authorisation to ensure that the science base, the toxicology
that has been done already, is sufficient to justify embarking
on this study in people.
Q39 Siobhain McDonagh: Thank you.
How many clinical trials does the MHRA examine before approving
a drug application? Is the MHRA confident that it completely reviews
all the findings necessary, both within and outside the public
domain, before licensing a drug?
Professor Woods: The legal responsibility
is on the applicant to ensure that in applying for a trial's authorisation
they do give us all the data, whether or not it is in the public
domain. That is clearly spelt out in medicines legislation and,
of course, it is fundamental to our assessment of a product that
we do have access to all the available data.
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