Select Committee on Science and Technology Minutes of Evidence

Examination of Witnesses (Questions 200-219)




  200. Just a comment about surveillance on viral disease. In, for example, gastroenteritis surveillance may not be important for treatment but it is crucial in vaccination strategy. Are there sensitive and accurate near-patient tests for viral diagnoses available to GPs, for example?
  (Dr Brown) It is very variable. There are at least four virus groups that cause gastroenteritis and give you identical symptoms so it is impossible to make the diagnosis clinically. There are widespread diagnostic tests for the most important of those, the rota virus and you will find all the local laboratories are able to provide that. For the other causes there are not diagnostic tests, except for electronmicroscopy, where that occurs, and that is a very inadequate technique for a number of these infections. So it is very variable.

  201. How long does it take a newly developed near-patient test to go through the validation process and get into clinical use?
  (Dr Brown) One probably needs to go back a step further, and that is to say: is there a commercial company that is interested in making the test? Do they believe they will make sufficient money from this to go through the very extensive developmental programme and validation and FDA approval if they are going to sell it and make lots of money? In the case of viral gastroenteritis, with the exception of the rota virus, which is the major cause of hospitalisation of infants, that has not proved to be the case. In terms of once the test is available, clearly different parts of the world handle the validation of that in different ways. It is still slightly informal within the European Community, although this is being tightened up over the next few years. I think the best way of validating these tests would be to use the evidence-based medicine approach, which is to say you have to do a study which indicates how that test result contributes to a change in what the clinician does with that patient, and those are expensive and difficult studies to do because they, by their very nature, require clinicians and laboratories, and the funding structure to do that is not in place. It is very much an ad hoc thing. You see much more rapid progress, for example, where there is an intervention, such as the influenza antivirals that were recently introduced. The company that made the antiviral also invested in producing near-patient tests that would accompany that to help focus the use of it. However, for the vast majority of viruses that situation does not pertain.

  202. On a point of interest for Dr Pillay, we heard about antimicrobial resistance to bacteria and about the use of microchips that could identify the major problem of resistance. Do the same exist in viruses against the antivirals and resistance developing in the antiviral field?
  (Dr Pillay) Yes. As we have heard, many of the viruses which are amenable to treatment cannot be grown. They are highly variable in terms of their genetic structure and, increasingly, it is the sequencing of large bits of the viral genome that has rapidly entered routine, clinical practice. This is an enormous advance. We are not just talking about PCR-based molecular tests, it is actually moving the sort of human genome sequencing project into diagnostic laboratories, and all the laboratories represented here would be undertaking those sort of tests. There are clearly commercial companies that can support that sort of provision but, equally, it is because of the cost—the enormous cost—(and here we are talking about orders of magnitude of cost over and above our existing tests), that there is a pressure for development of our own methodologies that can then be circulated around and tried within different laboratories in the network, as David has mentioned with some other tests. That is a major advance in that whole area. If you do not mind me very briefly skipping to a later question which pertains to this, the key is how we can utilise IT and so-called bio-informatic advances to utilise that sort of data in public health. That is the challenge at the moment.

Lord Oxburgh

  203. This may be too far in the future but to what extent is there any possibility of recognising viruses, not via the clearly very expensive and advanced techniques that you are talking of at the moment but going one step further and actually looking at secondary changes in body chemistry which may be indicative of the presence of a particular virus that may indeed be much more rapidly detectable once you know what they are?
  (Professor Griffiths) There are some theoretical possibilities. For example, you might look for interferon production as an area of generic response to indicate the presence of a virus as opposed to bacterial infection. In practice those have not turned out to be very useful when looked at but it is an interesting idea. We tend to focus on the individual infectious agent and you are encouraging us to look at more generic classifications and dichotomy for these infections.
  (Dr Zambon) I believe there are a number of big pharmaceutical companies who are interested in the concept of a dipstick test which will allow discrimination of bacterial and viral infection based on an innate immune response. However, I think that that will require substantial investment and is unlikely to be available from the public sector. If it is successful and being brought into the health centre, it will require some form of public-private relationship to bring it forward. It is a huge project.
  (Dr Pillay) I would just add that although it may be useful to identify a more generic method for diagnosing a virus, there is a huge range of different viruses but not only that, one of the peculiarities about virology is that a clinically important virus is identified every few years and has been for the last 20 or 30 years, especially with the onset of more molecular methodologies, and we want to be in a situation to identify and diagnose specific viruses for the purpose of intervention, for instance antivirals.

Lord Patel

  204. To a degree you have covered some of the points I wanted to raise in terms of surveillance, public health and policy making, but it might help to clarify one or two points you have made. My question concerns surveillance systems related to viral infection and how effective they are in informing public health policy decisions. If they are not, how could you improve it? If you suggest a method of improving it, what evidence base is there for that?
  (Dr Brown) Perhaps if I start with that question. I think the picture is quite variable. Probably the key issue for distinguishing good and effective surveillance programmes from other ones in my experience has been where you have an intervention that you are applying such as vaccination. You can then focus your surveillance on generating the data that will inform the policy you need for your vaccination programme. With MMR that is exactly the case. We have a surveillance programme based on measuring the coverage and the proportion of people who should be receiving the vaccine who do. We have a second programme which is aimed at identifying measles, mumps and rubella cases in the community and how well is our community protected from those infections. We have a third programme which is based on measuring the serological profile to those different infections in a representative population to find out whether there are groups within the population that are susceptible. We also have some adverse events monitoring and we monitor the cohorts, that is stratified immune profiling, which together with what we are seeing in the community and the predictions which come in the coverage enable us to make very precise, forward-looking models of what is likely to happen. Those have been used very effectively to steer the vaccination programme, so I think that is a good example. We have already discussed the problem of what is the burden of disease due to different enteric pathogens and how can you prioritise your efforts unless you understand that basic principle. We discussed that in primary care where many of these cases occur and we have very little idea as to how important each of these infections is. We are collecting some information on that from laboratory reports but it tells us almost nothing about that. Probably the difference between those two is that with a vaccination programme you have a very precise question so you can actually design the surveillance need and fulfil the circle in that way so that the two feed back into each other. If you look across the range they are very variable.

  205. Can I have a supplementary because I thought in the evidence that Dr Zambon has produced you were a bit sceptical, maybe that is too harsh a word, of the surveillance. What should drive the surveillance? Should we ask the question or should it be a passive collection of data and an aggregation of that data that drives it?
  (Dr Zambon) I think Dr Brown has answered this question very much as I would have done. The only thing I can add to that is there are examples where we collect data nationally but we do not use it. There are a good number of examples there. There are also examples where we do not collect data which could be useful to us, for example, on travel associated infections, where we do not really have any qualitative data on malaria in this country in the sense there is not a national reporting system, there is not the application of standardised reporting or data collection, and there is not a systematic surveillance system, and the reason, if you will, for the scepticism is that we can identify the problems that we know exist already but we are very unclear about how they may be improved and how things are to be improved under the new agency due to start on 1 April. Indeed, we are concerned about how things that are already good like measles, mumps and rubella surveillance and some aspects of, for example, the influenza surveillance programme are to be continued without a clear mandate for a strong central lead. It is my belief that the surveillance systems which we can identify as being good, indeed excellent, not only on a national scale but internationally as well, have two additional components, a strong R&D element which informs the application and use of technologies, often cutting edge and, secondly, a strong central lead. These elements are not clear in the papers with respect to the introduction of the HPA as to how the strong central lead for national surveillance programmes is to be maintained. There is a great deal of talk about regional data collection, regionalisation, but how is that to be integrated in the national picture? So I think I would summarise it by saying there are some excellent surveillance systems, some systems where the information collected is partial and does not always address the question, some and systems we do not collect the right data in order to inform the policy, and I am not at all clear any of this is going to be improved in the HPA.

Baroness Warwick of Undercliffe

  206. I wonder if I can look at another aspect of public health campaigns and ask you whether they rely too much on attempting to modify behaviour given the evidence that we have that these campaigns often fail. In your evidence you express concern that strategies, and you particularly refer to the sexual health and food preparation strategies, are based on attempts to modify behaviour and yet surveillance does not take those strategies into account at all in order to monitor effectiveness. I think you go on to question whether substantial amounts of public health money may be spent in ways that do not provide evidence of their usefulness. Could you comment on how the links between public health campaigns and surveillance might be improved?
  (Dr Brown) I do have some reservations about behaviour modification, not solely based on my own experience of my inability to change when I might wish to. I think both the sexual health programme and the recent Food Standards Agency initiative have good features of them, namely they have good process evaluation and at the end you will ask people has your behaviour changed, and I have always found I have never been completely convinced that that is a very good and robust method of establishing behaviour change. I think there are two separate questions, the first is that the best way to spend a limited budget without a validated method for making a difference and I think that still could apply to behaviour change. I think the two things that could make them more justifiable would be that there had been a proper trial to demonstrate, firstly, that you could make a difference and that you had a marker that you could use to indicate that change. For example, in the Sexual Health Strategy you might identify the HIV incidence or perhaps even better as a marker of behaviour change the herpes simplex virus because its acquisition is directly linked to sexual behaviour so you have an objective marker. You have to do a trial first because obviously you do not go straight to population interventions, likewise with the handwashing programme that is being broadcast at the moment. There are process measures in place but is that a good way of measuring that you have made a difference? I am not sure that it is. It is a question of prioritising the fairly major expenditure that follows on from advertising programmes against the other interventions that are available.

  207. Can I follow up with one brief question. There is also the question of whether there is value in itself of raising awareness. We have had evidence from Dr Nick Beeching that in the recent chlamydia campaign there were measures in place to demonstrate that awareness had been raised but the incidence of cases rose. I wonder whether again you could comment on that because I think it really is quite difficult to look for those sorts of objective ways of measuring whether, even with increased awareness, it has resulted in changing patterns of behaviour?
  (Dr Brown) Clearly there may be increased awareness. Quite how you measure that, again, is a good question. In a way you have answered your own point, if the awareness was there but the acquisition was greater it seems to me that was not necessarily a valuable addition to raise awareness and catch more of the disease.


  208. Any other comments, gentlemen? Dr Pillay, I missed your eye on the previous question. Did you have any final comment to make on question six before we move on?
  (Dr Pillay) The only thing I would add is to agree with both Maria and David about the patchiness of surveillance systems so where there have been historically very strong links between epidemiologists and sentinel surveillance then I think there is no doubt that that has been very successful indeed. But as we in virology are able to do more and more things to not only diagnose infections but ask quantitative questions about the nature of infections, the strain, the differences between individuals, and the amount of the virus and so forth, then it allows far more sophisticated surveillance to be done. We are in a situation that on 1 April we do not know what the structure of national laboratory surveillance will be within England and Wales. I think given that uncertainty and the huge demands there are on the potential where, through the networks, we are developing the ability to generate data link constructively and be forward looking with epidemiologists, there is a danger that will be compromised.

Lord Haskel
  1. Just on Lady Warwick's question, question seven, would you like to comment on whether campaigns to modify public behaviour on the grounds of health actually fail. I was thinking about smoking. It seems to me that smoking has been a campaign which has been quite successful.
      (Dr Brown) I am sure you should speak to your social scientist representatives. The time-frame for that success is perhaps quite a long one.

Baroness Finlay of Llandaff

  210. I am concerned in terms of the relationship between public health medicine and the virology services. With all the changes occurring, who is going to be in charge of epidemic management?
  (Dr Brown) Not me!


  211. You were making comments about the situation in England and Wales. We know that other parts of the British Isles differ but what about Europe, are they better organised on the continent of Europe than we are?
  (Dr Zambon) Recently, it has often seemed ironic to a number of colleagues and myself that we are being asked to speak at international meetings and for us to elaborate on how good the UK surveillance systems are, when we are in the process, apparently, of dismantling them. In respect of influenza, respiratory disease and respiratory viruses it is clear that the UK, along with France and the Netherlands, have the most advanced systems but what is also becoming clear over the co-ordination of Europe activities is that there is going to be much more investment into the development of sentinel primary care systems in Europe for the development of disease and syndrome specific information linked to clinical diagnosis, so a great strengthening of the primary care infrastructure.

  212. Who would do that co-ordination within the European Union?
  (Dr Zambon) As far as influenza and respiratory viruses are concerned, there is representation at every level from every country by both epidemiologists and virologists, so there is usually a pair per country who are responsible for the aggregation of national data. These are being brought together with EU funding to develop the regional networks, regional in this case being regional European networks. Influenza is a particularly well-developed model but I think there are other examples so there is a great deal more co-ordination work in Europe. I think it is also fair to say that some European countries where there have been very decentralised approaches to epidemiology have recognised there is a greater need for centralisation. Good examples there would be Spain and Germany.

Chairman: Any further points? If not, can we move on to question eight.

Lord Oxburgh

  213. We have talked about IT and touched on it a number of different times during today's session. Clearly none of you were actually satisfied with the IT arrangements in place at the moment. Would you like to say what you think they should be? The NHS has recently announced it is going to spend very large amounts of money on IT and there is a new IT director. What do you think they should be doing from your point of view? As a corollary, one of the new pieces of information for surveillance which is now regularly available is the response pattern to NHS Direct. I just wonder if any of you have used the monthly patterns that emerge from that?
  (Dr Zambon) Perhaps I will start because we are likely to all have comments. It is important that whatever IT systems are developed they do talk to each other. One of the greatest difficulties has been trying to work with a data set from one system and translate it into another system. Based on the remarks with respect to primary care, there is a need to link diagnosis in primary care with prescribing in primary care. It is quite interesting that at the moment the information capture of prescription in primary care involves one system whereas with sentinel practices we have been involved in trying to acquire information on microbiological diagnosis and that has involved a separate system. What one would like to see in terms of developing data on disease burden and also on antimicrobial resistance is a system which allows linkage of information not only of consultations but also sampling, results and prescriptions, so we have a fully integrated IT system in primary care which then can link to what goes on in local hospitals. That is very much a comment with respect to service delivery but then there are also important IT elements required for information exchange at national and regional level and there the emphasis needs to be on systems talking to each other. I am sure Dr Pillay will say things about the requirement for bio-informatics and the requirement for a national data set there.
  (Dr Pillay) Before I get to that I would say in the UK we have a unique opportunity because there is the National Health Service framework into which both PCTs and trusts fall. Private work and private laboratories make up only a very, very small proportion of the work undertaken within the UK so we have with this new NHS initiative an ideal opportunity to capture truly national data. There are not many countries in the world who can do that. So really the challenge is to optimise that. It seems to me there are two areas of IT demand, the first is to be able to integrate clinical data/denominater data in order to give a truer perspective on positive diagnoses which currently we do not have, and Maria has discussed that, so I will not go over it. The second area in terms of virology—and I have alluded to this before—is the complex nature of the data that we are now generating in the laboratory. Unfortunately, many of the existing surveillance IT systems allow for a diagnosis yes or no. Really just talking from my own area of expertise in terms of HIV drug resistance, there is more HIV in the UK than ever before, there are more diagnoses, there are more imported infections, there are more treated infections, there is more resistance developing. In order to capture these parameters we have the opportunity to get data from all virology laboratories so we have the potential to have a handle on every HIV resistant virus within the United Kingdom. That is a challenge. The ability is there for us to merge data. The software requirements needed to do that are challenging but certainly should not be insurmountable, and I would argue that what is now the case with HIV and will soon be the case with hepatitis C, and I am sure David will talk about other areas of molecular epidemiology where they are looking at the gene sequence of various organisms to look at transmission events and circulation within the country. So I think there are major demands which I would hope could be fulfilled.
  (Dr Brown) I think the question of the interfaces between different IT systems being bridgeable is one critical issue so that information can be shared. To respond briefly to the question of how one is able to use the sequence data that we can now generate, clearly one issue is that you need to use the same technique across the country and active management of that is critical. The second is clearly web-based reporting and web-based analytical tools are now starting to be used much more widely. I am involved with one of those and there is the potential to enable much more rapid exchange of this much more complex information.
  (Professor Griffiths) To follow up a point Dr Pillay made about the HIV side, and this links back to your question 6 really, it would be quite crucial to know which sub-types or clades of virus are circulating in our country and to start trying to anticipate potential antivirals and HIV vaccines because some of the those will protect against some types of HIV and not against others and it is quite important to have that in hand now as you look forward a few years to those policy decisions.

  214. None of you commented on NHS Direct and whether you found any useful patterns emerging from that.
  (Dr Zambon) I believe NHS Direct has received some funding for research and development for evaluation for its use as a surveillance system to assist in recognition of influenza. I think the data so far are preliminary and I am not sure that a clear conclusion can be drawn as yet. One of the things that I believe is being explored is whether or not there can be some form of sampling linked to NHS calls because one of the problems is specificity in the system and how to actually use it in a very specific way. My experience of NHS Direct is limited to that related to respiratory diagnosis.
  (Dr Brown) I think the point is that it is still early and perhaps unproven and you can see the problems you may have with syndromes caused by 25 different infections. How do you interpret what that means, particularly for things that are widely prevalent in the community anyway? How do we use it to detect specific epidemics which are due to one individual cause when there are 20 others? I am sure it will have a useful role but we are not quite there yet from my perspective.

  215. All of you have been asking for more information. Have any of you had any experience of being overwhelmed by the amount of information you have?
  (Dr Zambon) One could say every winter!

  216. Because the management of this information if one gets good IT systems in place becomes critical and you can become overwhelmed by it to the extent it is no longer useful.
  (Dr Pillay) As someone who runs a national reference unit, a major challenge for me and my team is to try and identify patterns within the data and to get some useful outputs out of all the information that comes in.

Lord Rea

  217. How are you succeeding in getting this useful information?
  (Dr Pillay) I resort to having to write grant applications to the R&D funding streams within the UK despite being within a PHLS structure, to deal with that precise area of data assimilation. We can generate the data; get the data from other laboratories, what we cannot do is look at it in a coherent way.

Chairman: Can we move on to the final question. Lady Finlay?

Baroness Finlay of Llandaff

  218. Some of the evidence that has been received expresses caution about rushing to use new diagnostic technologies because of a lack of robust evidence about their effectiveness. Do you concur with that opinion or do you think we should be exploiting and pushing forward the frontiers and using some of the new technologies more?
  (Dr Brown) I think we should certainly be moving forward and exploiting it. "Rush in" is not a phrase I would use. I think "orderly forward progress" would be a more appropriate way of describing it. Clearly we touched earlier on the issue of how you validate those tests and it has to be in the context of evaluation of patient management which are complex evaluations which will take some time to do for a range of these techniques.
  (Professor Griffiths) I am not so sure what you mean by the use of the word "new". Do you mean PCR and molecular tests related to it?

  219. I think one also has to look ahead to other things which will emerge in the future. We have had a bit of a discussion now just in terms of the general principle of should there be some form of control mechansim in the new techniques rolled out in the context of a trial which is fully resourced and funded as a research programme to validate it before it is more widely rolled out into clinical use?
  (Professor Griffiths) That is something we are very keen on in the network side, that there are enthusiasts of assays for their own particular markets and within target populations. What we would like to do is to leave behind the ones that did not work and roll out the ones that have been fully validated. There is no point in reinventing the wheel. We could use that resource for everyone in the UK.

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