Examination of Witnesses (Questions 540-559)|
TUESDAY 11 MARCH 2003
540. Are the seven companies in UVIG mixed in
the sense that they manufacture vaccines as well as therapeutic
drugs, or are there some of them, or others you might know of,
which solely manufacture vaccines?
(Mr Kingston) We are mixed; from one extreme to the
other. Powderject is a member of UVIG and Powderject is exclusively
a vaccines company. At the other end you have companies such as
Wyeth and GlaxoSmithKline, for whom vaccines are an important
division, but it is perhaps five or 10 per cent of the total company.
Lord Lewis of Newnham
541. What is the rate of increase of interest
in this particular problem? You are talking about the present
day. Let us take the position five or 10 years ago. Were those
figures more or less the same then, or have you seen an increase?
(Mr Kingston) Quite a dramatic increase. UVIG membership
has gone from zero five years ago to four and now seven. That
is a reflection of the level of interest from companies in promoting
vaccines in the UK.
542. How would you expect that figure of 5 per
cent of overall R&D expenditure to change? During earlier
stages of this inquiry, we have been given figures that somewhere
between 40 and 60 per cent of the causes for people consulting
doctors are in fact infections.
(Mr Kingston) It would be a function of how many scientifically
credible routes of exploration there are and simultaneously a
function of dialogues with the paying authorities as to how many
vaccines they would contemplate funding and the practicalities
of administering the programme. It is very much one thing to say
we have the money and the policy, but until you can deal with
the practicalities of getting all your population vaccinated,
you may not get the results you want.
543. May I just put to you this 5 per cent of
spend which you mentioned? Bearing in mind that immunisation is
probably one of the most effective ways of controlling infectious
disease, it does seem a minor amount of effort is being put into
immunisation and vaccination compared with all the other spend.
How would you respond to that statement?
(Mr Kingston) I would respond to it by perhaps suggesting
there is an alternative way of looking at it which would be to
say that there are currently licensed and available many more
vaccines against a number of more diseases than are actually actively
promoted in the UK vaccination policy. We do not want to create
a situation where industry develops and makes available a number
of vaccines which are subsequently not used as quickly as we would
like. At the moment we feel that more vaccines have been developed
and launched than have found their way into being implemented
Lord Lewis of Newnham
544. Why would this be? Why would there? Was
there not sufficient investigation made about the need or requirement
of these things?
(Mr Kingston) Clearly not, is the short answer. We
have already spoken about the meningitis C development work in
the UK and I think we are probably united in saying that is an
example of how good it can be when there is clear dialogue about
what is required, what the steps are. It is a fantastic result.
There are other vaccines available, for which that level of dialogue
either has not happened or companies from an industry perspective
have received mixed messages and companies have invested something
and all of a sudden that clearly was not the priority vaccine
to bring to the UK from the Department of Health's point of view.
545. Can you give us some examples of that?
(Mr Kingston) In terms of vaccines which are available
but not used as well as they could be, there are vaccines against
pneumococcal infection for the elderly, there is a vaccine against
varicella for healthcare workers and mothers-to-be who have never
had chickenpox. Hepatitis B vaccines are widely available, but
the uptake amongst the at risk population is pitifully small.
The primary care system finds it very hard to track them. There
are developments and vaccines available in the infant schedule
for strep infection, the Prevenar vaccine from Wyeth is available
but has not yet received a full policy endorsement. We are waiting
for changes to the type of pertussis vaccine used, the type of
polio vaccine used, where the UK policy is slightly different
to the rest of Europe and broadly speaking other developing markets.
Lord McColl of Dulwich
546. In summary then, this rumour that companies
are not interested too much in this is not actually true. You
(Mr Kingston) Yes.
547. Have there been any areas where there has
been a serious shortage of any particular vaccine? Just to put
the record straight.
(Mr Kingston) There are occasional shortages in supply
of a vaccine which we all strive not to bring about, but it does
happen from time to time. There are known priorities published
by the Department of Health of vaccines which they would like,
which currently are not available. There is a case for matching
what is bought to what is required.
548. We move to something which might possibly
be the answer to the sad tale you have just told. How well co-ordinated
is vaccine development and epidemiology in the identification
of priority areas for vaccine development and the surveillance
of disease, both before and after the introduction of vaccine
(Dr Miller) This is something the PHLS leads on: identifying
both the burden of disease that is potentially vaccine preventable
and then monitoring the impact of vaccines once they are introduced.
I have to say in relation to the non-utilisation of vaccines which
are licensed, these were vaccines which were developed for a global
market and the decision perhaps not to use them in the UK is based
on the particular epidemiological situation in the UK, where the
burden of disease and the potential gains from vaccination in
relation to the cost do not look that cost effective in relation
to other ways of buying quotas or preventing premature death.
It is not a question of developing them in partnership with the
UK and they are not using them. There is a very careful evaluation
of the burden of disease and the need to justify the use of a
vaccine or spending public money to achieve a health gain through
vaccination, because clearly that is an opportunity cost and the
money could be spent elsewhere to achieve a similar health gain.
There is a very careful evaluation of the cost effectiveness of
introducing different interventions and just because a vaccine
is available, does not necessarily mean that it is a good way
to use public money. Overall perhaps what could be done a little
better is having a better sort of evidence based prioritisation
of disease burden. This has been something on which the Medical
Research Council produced an expert group some years ago to ask
whether there was any way we could prioritise better. One of the
things which was identified was a very robust evidence based quantification
of the burden of disease due to different potentially vaccine
preventable targets. We have not done that in as robust a manner
as we could do. PHLS has what is called its overview of communicable
disease each year which sets priorities. That is very much based
on the Delphi technique: if you ask a lot of experts, you might
get head lice at the top of the list rather than something which
is really preventable.
549. What happens to that then?
(Dr Miller) It has been used in the PHLS to prioritise
development monies, for instance particularly R&D monies.
We recognise that although it would be a very major investment
of resources, we could do it in a better way and rather than having
people's opinionsand we did canvass a lot of opinions from
primary healthcare to hospital-based consultants, public health
doctorswe could have access to disease surveillance data
which would allow us to put both a morbidity evaluation plus some
economic evaluation of the impact of that disease and to prioritise
according to the stringent criteria which would apply across the
board. That is something we hope to do within the new Health Protection
550. I am still a bit confused because my sense
is that we do need quite a lot of vaccines and now we are hearing
that we have more vaccines than we need or we use. Can you tell
me where the position is in relation, for example, to R&D
in the UK into diseases like HIV and TB? I am sure money is being
spent in this area, they are both high in the public's gaze, and
vaccines for these would be very helpful. Malaria too, although
it is not a UK problem. These are big gaps in our armamentarium,
these are big killer diseases. Are we spending enough on this
(Dr Miller) I am not aware of what is being spent
in the private sector. Certainly CAMR has an HIV and a TB vaccine
development programme. Academic institutions with particular expertise
are looking at various constructs. There is a lot of potential
for developing vaccines based on new technology such as DNA vaccines
and so forth. Perhaps some of the views you had from the Royal
Society was that there was a big expectation perhaps a decade
ago that all these new technologies, reverse generics, DNA vaccines,
vector vaccines were suddenly going to have an explosion of candidates,
that HIV would be picked off. Technically it has been more difficult
than envisaged, though there is a feeling that it has not borne
fruit, but that is a recognition that despite a lot of research
effort, some of these candidate vaccines are jolly difficult to
achieve. I do not have a dossier of all that is going on in the
UK in terms of research into HIV, malaria; meningococcal B is
clearly an important vaccine for the UK. It is not easy. The easy
candidates have already been picked off.
551. Are we spending enough in this area?
(Dr Chatfield) It is right to say that the easy areas
have already been picked off in terms of vaccines which are currently
licensed or in late stages of development. With HIV in particular,
several companies have fallen on the sword of HIV in terms of
the early expectations and the amount of money which went into
that at an early stage. You have seen recently another vaccine
for HIV has failed in phase 3 in the US. These are very tough
areas. That is not to say there is not a lot of research going
on. The same is true for looking at new ways of identifying antigens
which could be used in TB vaccines as well.
552. As you know, this Committee produced a
report on development of resistance to antibiotics. What part
does that play in decisions among vaccine researchers and purchasers
and manufacturers as to how to direct their efforts?
(Mr Kingston) The subject of antibiotic resistance?
553. Yes. If you can vaccinate, then you do
not need to use the antibiotic.
(Mr Kingston) From the big pharma perspective the
issue of antibiotic resistance is well understood and there is
lots of work about rational prescribing and all that kind of stuff.
I cannot say that the fact of antibiotic resistance really drives
a vaccine research programme. A vaccine research programme would
be antigen specific: is there an opportunity to protect against
a given disease with a vaccine? Then the programme would unfold
or not, I would say, independently of any antibiotic resistance
554. What about pneumococcus or streptococcus?
(Dr Miller) It was not the main driver. It would be
an ancillary argument to say why it may have additional cost benefit
that if there were, for instance, a rising antibiotic resistance
to the major sero-types which could not be addressed by the other
methods which had been put in place to limit unnecessary antibiotic
prescribing. That might be an additional factor that you would
weigh in the cost benefit argument. It was not the main driver
for developing that vaccine.
Baroness Finlay of Llandaff
555. Can we pull out a specific example? We
know there is a huge disease burden from MRSA. Is that something
which is in the frame at all, or not?
(Mr Kingston) From UVIG's point of view, I should
have to request permission to give you supplementary information
to that question.
556. It is just a specific example where we
have heard of a disease problem.
(Dr Chatfield) There are certainly some programmes
ongoing at an early stage in terms of looking for ways of preventing
staphylococcal infections, for instance in a hospital environment.
Several groups are examining passive immunisation, looking at
using antibodies rather than active vaccination. In those areas
there are certainly smaller companies and smaller groups addressing
the matter. It is at an early stage.
557. May I just ask about UVIG? Do your companies
co-ordinate, collaborate, share information or do they work more
or less independently?
(Mr Kingston) The mission of UVIG is to promote the
public health benefit of vaccinations and to represent the vaccine
industry in the UK to interested parties such as this. When you
are talking about the R&D programme and the commercialisation,
we are then talking about a competitive industry. UVIG would quite
properly not be a forum for sharing information of that type.
It is done on bilateral discussions between individual companies
and the opinion policy formers around the world.
(Dr Miller) There is some in the European Vaccine
Manufacturers' Forum. I have certainly been to conferences which
have been sponsored by that group, which have brought together
biotech companies, big pharma companies, public health individuals,
so we can see the potential for areas of cross-fertilisation.
I do not know whether that is done on a UK basis, but it has certainly
been quite successful at a European level.
Lord Lewis of Newnham
558. You have already mentioned that vaccines
are monitored. Can you describe how vaccine safety is monitored?
(Dr Miller) Yes. The routine system is through something
called the yellow card reports, where there is a statutory requirement
for medical practitioners, which has now been extended to nurses
and pharmacists, to report on a yellow card reactions which are
suspected to be causally associated with vaccination. We know
that the system is under-reported, that there is patchy reporting,
but nevertheless no country has come up with a routine system
which is any better. You have to have some kind of signal detection
device and that comes from the passive spontaneous reports through
the yellow card system. When a new vaccine is introduced, it usually
has a black triangle status, which means that any suspected reaction,
however trivial, should be reported. That is very important from
the point of view of generating hypotheses about rare events which
may not have been detected in pre-licensure trials. Once there
is experience with a vaccine in routine use, that yellow triangle
status is removed and there is only a requirement to report severe
or unusual adverse events. That is the underpinning system. Clearly
it is looked at in detail by the Medicines Control Agency. If
problems are detected, so a hypothesis may be generated from that
system, or indeed a hypothesis may be generated by an interested
clinician coming up with a series of cases that he thinks may
be demonstrating a particular syndromic relationship with vaccination,
then there are various ways of testing hypotheses about vaccine
safety and analytic epidemiological studies for which PHLS has
a remit. We do not have the remit for monitoring vaccine safety,
but we certainly have a remit for investigating safety concerns,
when these have been generated by the means I have described.
There are other academic institutions which will take an interest.
For instance, many years ago when there were concerns about pertussis
vaccine, Professor David Miller, at an academic institution led
the major research initiative to investigate the allegations about
vaccine safety. Prescribing doctors are also required to report
to manufacturers adverse events which are suspected to be vaccine
related. There have been discussions as to whether or not the
yellow card system could be improved by having the system in the
States, where anybody can report on the yellow card, parents for
instance if they suspect a vaccine reaction. There is a set of
conditions which is mandated for reporting and a 24-hour toll
free helpline so that anybody can phone up at any time of day
or night. It has been looked at in some detail and the analysis
which has been done has not shown that the American system, although
it looks better, is actually generating more signals or has increased
sensitivity than the yellow card system. In addition it generates
a lot of noise. A lot of countries have looked at the system and
decided that it is okay for the Americans to do but it would be
better to have more highly developed systems for conducting analytic
studies when a hypothesis arises. In that context, the PHLS has
developed and has been developing over the last decade, record
linkage methods using computerised data sets where we can link
immunisation records with clinical event databases, either general
practice ones or hospital admissions and look for patterns of
hospital admission or consultations in predefined risk periods
after vaccination. That has been very successful and has underpinned
a lot of the work the PHLS has been able to do investigating concerns
about MMR vaccine safety. That is something I could see being
559. What about the possibility of synergy?
(Dr Miller) How do you mean "synergy"?