Select Committee on Science and Technology Minutes of Evidence


Examination of Witnesses (Questions 540-559)

DR STEVE CHATFIELD, MR IAN KINGSTON AND DR LIZ MILLER

TUESDAY 11 MARCH 2003

Lord Rea

  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.

Lord Oxburgh

  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.

Chairman

  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 in policy.

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.

Lord Turnberg

  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 have overproduced.
  (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.

Baroness Walmsley

  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 programmes?
  (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 opinions—and we did canvass a lot of opinions from primary healthcare to hospital-based consultants, public health doctors—we 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 Agency.

Lord Turnberg

  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 area?
  (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.

Lord Rea

  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 concerns.

  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.

Chairman

  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 developed further.

  559. What about the possibility of synergy?
  (Dr Miller) How do you mean "synergy"?


 
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