Oral evidence: Antimicrobial resistance, HC 848Wednesday 12 March 2014

Oral evidence, 12 March 2014.

Witnesses

George Eustice MP, Parliamentary Under-Secretary of State for Farming, Food and Marine Environment, Department for Environment, Food and Rural Affairs, Jane Ellison MP, Parliamentary Under-Secretary of State for Public Health, Department of Health, Professor Dame Sally Davies, Chief Medical Officer, Department of Health, and Professor Peter Borriello, Chief Executive, Veterinary Medicines Directorate, gave evidence.

Chair

Good morning. Thank you very much for coming. Just so that our viewers can understand the oddities, you are sitting slightly lop-sided for a deliberate purpose, because one of the microphones died down at the other end of the table. First of all, can I welcome Ministers to the session? This has been an intriguing inquiry and we are coming to the end of it, so your evidence is hugely important. Can I ask you both whether you see antimicrobial resistance as a top priority for the UK Government?

Jane Ellison

Yes, certainly. From my point of view in the Department of Health, it is pretty much the first conversation I had when I took up my ministerial post in October last year. I think probably on the second day I was in post I had a conversation with Sally about it, and I have carried her book in my handbag ever since to remind me of its importance. It is something I have raised on a number of occasions with international colleagues in debates. So, yes, it is a real priority and it is being given very high priority through the high‑level steering group and the work the Department of Health is doing.

George Eustice

Yes, I would agree with that, and obviously DEFRA is working closely with the Department of Health on this issue as well. I know that Dame Sally Davies has made a very strong case that this is an issue. We think the evidence suggests that actually antimicrobial resistance on antibiotics used in humans tends to be distinct from those used in veterinary practice. While there is a potential for crossover, the evidence so far is that there is not a huge amount of crossover, but it is something that we are not remotely complacent about, and it takes up a big part of our research budget at the VMD.

Chair

Having agreed with the chief medical officer, Minister, do you agree also with the chief medical officer’s view that antimicrobial resistance ought to be on the national risk register?

Jane Ellison

Yes, I do. We are working very hard to make sure it goes on there, and I think we have a fair degree of confidence that it will be seen in that context. But, yes, I agree that it should, and we will be preparing submissions this spring for the next round of consideration.

Chair

That would mean, logically, that in the next register published after that you would expect it to be public.

Jane Ellison

I would very much hope so, yes.

Chair

But given this strongly held view, both by the chief medical officer and by yourself, one would hope that in practice the Cabinet Office will be treating it as if it were on the register now. Would you not hope that?

Jane Ellison

If you look at the priority it is being given right across Government, and from the top of Government, that is the de facto position. For example, when we were leading the G8, we had a summit alongside the G8 last June, which brought together G8 scientists to discuss this. The Secretary of State for Health has raised it with partners internationally and, as I say, right from the top of Government, from the Prime Minister downwards, it is taken as a really important priority. My own view is that there is no question that it is not on the national risk radar already, even if it is not yet formally on the register.

Chair

Putting it in a historical comparison, you would not foresee the kind of gap in taking action that there was, for example, in pulling together the right expertise around the volcanic ash episode. You think the work is done already.

Jane Ellison

The work is well under way. Clearly the work is not done, because we face a very significant threat, but because we have had such dynamic and senior leadership from the chief medical officer, and we have lots of the strategic groups in place and there is complete buy‑in from all levels of Government, there is nothing in the way of us following through on this as a priority.

Chair

There is no resistance from the veterinary side.

George Eustice

No resistance from us at all. As I said, we take this seriously. Although the evidence is that antimicrobial resistance in animals is low—there have been some cases—we are not at all complacent, because we absolutely recognise that overuse of antibiotics can be a driver of that resistance. It is why we commit quite a bit of our research and development programme at the VMD to that.

Stephen Mosley

The first UK antimicrobial strategy was published in 2000, and, while the evidence we have seen saw nothing wrong with that strategy, we have heard quite a bit of criticism about the implementation of it. We have heard evidence that as many as 20 of the recommendations were never implemented, and there are concerns that it did not have the funding or the infrastructure to deliver. You published the 2013 to 2018 five‑year strategy last year. What are you doing to ensure that this strategy is a success and that it is actually implemented this time?

Jane Ellison

Obviously, I was not around when the previous strategy was in place, but it seems to me that the key components you need in place are clear leadership and a clear sense of direction, which we have from the top from the chief medical officer, and you need substantial Government commitment, and you have that as well. All the expertise has been brought together in the high‑level steering group that sits behind the strategy. We have all the right people round the table, and also we are working across Government. I think that is really important; this is everyone’s business. All the building blocks are in place. The next stage is obviously to move to an action plan with metrics, which we will then judge against annual reports. If you put all of those things in place, you hard‑bake in the momentum to the strategy. If we are failing against 20 items or whatever, by this autumn when we have published the action plan and the first update on the strategy, we will have to confront that and we will have to do better.

Stephen Mosley

Will the high‑level steering group have the teeth to be able to publish this and confront you as Ministers and say, “Look, you are not delivering what you promised”?

Jane Ellison

Yes, definitely. I have absolutely no sense at all that if Ministers were not responding adequately to the priorities put down in the strategy, the chief medical officer and others would not make us aware of that, and that is quite right.

Stephen Mosley

The new strategy is very much focused on antibiotic resistance. From some of the evidence, we heard concerns about the dangers of overlooking viral and fungal resistance as well. Have you considered those two aspects, and do you think there are dangers of overlooking fungal and viral?

Jane Ellison

I am aware that that is a concern. I am not a scientist by background, so there are areas where I need to defer to those who have the technical expertise, but I am aware that that is a consideration. Again, I think it is one that has been considered and is very much part of the thinking of our high‑level steering group and all the people involved in thinking about this. I do not think it has been overlooked.

Stephen Mosley

As the research or the evidence changes—if during the plan period of the next five years, you see there is an increased focus on things like viral and fungal infections and resistance—would you have any sort of review point within the five‑year strategy to say, “Look, we need to make some alterations here,” or is it a five‑year strategy that you are going to go ahead with and judge at the end of it?

Jane Ellison

The fact that we have committed to annual updates and an annual report against the metrics, once those are published later this year, means we have plenty of pulse points within that five‑year period to make those adjustments if we need to.

David Tredinnick

I want to look at alternatives to antibiotics if we fail to produce any new classes of antibiotics. Have you considered what your approach may be if that is the case—that we fail to produce new classes of antibiotics? What are we going to do?

Jane Ellison

I have not given a huge amount of thought to that at the moment, because one of the key strands of the strategy is to encourage the pipeline for new drugs. I know some thought has been given to, for example, herbal medicines—I believe the chief medical officer has responded on that—but our principal aim is the three key strands of the strategy, which are preserving what we already have that works, looking at the pipeline and making sure that we do not compromise the potential in the future for things that can actually make a difference. It is not something I have given a lot of thought to, because I do not think we are at that stage yet.

George Eustice

On the veterinary side, the VMD funds a number of projects looking at antimicrobial resistance, and I think two of those have an element looking at some alternative treatments. There is a range that may provide some enhanced immunity. There are the prebiotics and probiotics, and internationally there is some research being done on that, and then other systems to try to improve natural immunity. The VMD is doing a couple of projects that have elements of that, but are not dedicated solely to it. One of the difficulties you sometimes get with these treatments, although anecdotally they have some impact, is that when you get to clinical trials they tend sometimes to fall at that final hurdle. But as I said, it is an area where we are doing some research.

David Tredinnick

We have indeed covered in the earlier session and in the Health Committee, on which I also sit, this issue of alternatives. I have discussed alternatives with the chief medical officer, and the Secretary of State as well. We have quoted tea tree and artemisinin—artemisinin is derived from a 2000‑year‑old Chinese medicine—and I suggest to you that what we actually need is more research into these options, so that we have some kind of fall‑back position. Also, we need to look at the research that has been going on since this Committee reported to the last Parliament on homeopathic medicine. Research at Toulouse university, about which I have been in an exchange with the Secretary of State, seems to show that where homeopathic medicine is used with allopathic medicine, two things happen: patient satisfaction goes up and the demand for conventional drugs, including antibiotics, goes down. I got the House of Commons Library to come up with figures for the National Institute for Health Research funding for 2012‑13. I think the budget is £209 million. Those are the most recent figures. Surely we should be spending some of that—not none of it—on looking at alternatives, given the absolutely dire situation about new antibiotics coming on stream. Should we not be backing other options—hedging our bets, to use a horse‑racing term?

Professor Dame Sally Davies

Perhaps, as that is a technical question, I can answer about research. Clearly if we got a good application to NIHR, both scientifically and methodologically, as I said before, we would be keen to fund it. What I have not told you before is what a lot of effort the Chinese are putting into herbal medicines. They have in Shanghai a very big institute that is taking their herbal medicines, looking for the active products and isolating them using HPLC and modern science. They were aware of artemisinin before the Wellcome Trust picked it up and developed it for malaria. As they have this big institute and this expertise, if there are things to be found, I am confident that they will find them.

David Tredinnick

It was helpful to have your response, but could I ask the Minister?

Jane Ellison

Mr Tredinnick, I keep an open mind. As a Minister, as much as possible I will be led by the evidence and by the guidance of my experts.

David Tredinnick

Just to finish on this area, the Health and Social Care Act—the big health Act that has just gone through—emphasises patient choice. Patient choice, according to conversations with the Secretary of State and from what he has said on the record, is to be at the heart of the health service. If we are going to have patient choice, we have to listen to what patients want. A lot of patients out there are very worried about antimicrobial resistance. They do not want to have antibiotics first; they want to try other things. Surely it makes sense that the Health Department tries to encourage people to use other treatments first. Surely if a general practitioner believes, in their clinical judgment, that going to a herbalist or a homeopath is a good idea, we should support that, because we are trying to reduce the consumption of antibiotics.

Jane Ellison

I have responded to questions probably a couple of times at Health oral questions, and we have always been clear that CCGs can prescribe as long as they prescribe against the normal criteria, which are value for money and efficacy. That is on the record in the House of Commons.

David Tredinnick

Thank you very much.

Professor Borriello

I think it is important to note that resistance is now emerging to artemisinin. Resistance can emerge to all things, and artemisinin is not against germs; it is against a different beast. Yes, of course there is a role for traditional in many aspects, and certainly for learning from some of the things that may have worked in the past, but it is also worth remembering that prior to the antibiotic era, the only thing that was available were all the alternatives and we know the consequence of that. There was a huge amount of morbidity and death.

Professor Dame Sally Davies

Forty-three percent of people died prior to the golden age of antibiotics.

Professor Borriello

That is not a reason to dismiss alternatives; it is a reason to apply the best science to learn from them, particularly in some of the old methods for managing wounds. Another important point is that in the veterinary field viral infections are not a major problem. We don’t use antivirals; we use vaccines. Antivirals are not traditionally used in veterinary medicine. On the human side, fungal infection, where resistance is a problem, is predominantly in the immuno-compromised. Although it is very important, it is not such a major issue numerically. There is some research on alternatives, including in the veterinary field. One area where there could be some mileage is on phage therapy—that is, viruses that kill germs—but there are some problems with that as well. It is not that industry is not interested. Of course they want new products that will be useful and give them a profit, so there is a lot of activity. The reason many of them do not come to market is that they do not work as well they should in practice or in general practice.

Mr Heath

I think what I am hearing, as far as Government policy is concerned, is that the Government retain an open mind to looking at unrefined drug applications derived from plants, or whatever, to identify active ingredients, provided there is efficacy supported by evidence, but that you are not in the business of supporting placebos as an alternative to fighting microbial infections. Is that correct?

Jane Ellison

I think it is right to say that we will be led by the evidence of what works, yes.

Graham Stringer

Do the Government attempt to co‑ordinate research into antimicrobials or antimicrobial resistance, and should they do more?

Jane Ellison

I will give a quick comment and then ask Sally to give the detail. I think there is a lot more effort going in to trying to co‑ordinate the research. This is one of the areas, certainly coming to it relatively new in the last few months, where I have seen an awful lot of effort, whether it is the themed calls for research or the attempt to co‑ordinate public and private funding. I think there is always more you can do, because we have a huge mountain to climb, but we are making a good start. The key is making sure we are getting the message out that we have to work internationally; this is not something we can do just in our country. That is one of the reasons, at an advocacy level, that I have raised it in at least half a dozen bilaterals, including formally with my opposite number in the Chinese health ministry at a recent conference in the Foreign Office, but I will ask Sally to comment on the detail.

Professor Dame Sally Davies

Clearly we need to co‑ordinate. We have some historical co‑ordination going back to about 2006, with the UK Clinical Research Collaboration and the Translational Infection Research Initiative where we funded seven centres across a lot of funders. There was our joint funding from the Department of Health with the Wellcome Trust, the Health Innovation Challenge Fund, funding nearly £3 million over three years in genomic technology to inform outbreak recognition and surveillance. Now, as I told you earlier, we have the new AMR research platform led by MRC, bringing in the research councils, and the cross‑Government antimicrobial research funders forum led by the MRC, that the VMD, the Department and all the funders, including the Wellcome Trust, have started to attend, to debate what needs doing and sharing the work out.

Graham Stringer

Do we need a centre of excellence devoted to this area?

Professor Dame Sally Davies

We need critical mass around certain issues, and that could then be called a centre of excellence, and we might need a number. The needs are different and the expertise may lie in different universities. More and more, we set up networks and collaborations. We need a single development pathway. We have just funded, as I mentioned earlier, two new research units to work with Public Health England on antimicrobial resistance. They are both units of excellence. We need quite a lot of different things, but they should collaborate.

Graham Stringer

In other areas—the Francis Crick Institute is just being developed, and there is the Hadley Centre and the Sanger Institute—people are bringing expertise and excellence together, simply so that people can talk and learn from each other’s research. Do you not think in an area of such importance as this that we should have the equivalent of those centres?

Professor Dame Sally Davies

Actually, no. The Sanger Institute needs its sequencing farm, so it is technology as well as science driven. The Crick is our national institute, and we are not going to recreate that. What we need to do is build on the expertise that is in many different places, many different universities, and then get it co‑ordinated and collaborating. I would argue that if we set up one centre, we would be leaving out some expertise that would not move. That would be a great pity.

Graham Stringer

That is a really interesting answer. If this problem is anything, it is an international problem. Do we need the equivalent of the IPCC in this area to look at the problem?

Professor Dame Sally Davies

I think it is very likely that, at the end of the day, we are going to need something along those lines, but there is a lot of work going on, initially at the WHO, with their resolution that we led, supported by 50 other countries—it goes to their Assembly in April—that will start a world action plan, a global action plan development, and I could imagine or envisage that an IPCC‑type mechanism might come out of that at the end of the day.

George Eustice

We need collaboration in two different directions, first of all between Government Departments. One of the key features of the new AMR strategy is the “one health” approach where you look at the connections between animal and human health and make sure that work is joined up. Secondly, you are right; internationally, the EU is co‑ordinating some work in this, and the VMD is, as I mentioned earlier, funding six studies at the moment which are part of a trans‑EU collaborative project. In addition, there are other organisations like the OIE and a committee on the UN that are doing some of this work. It may be that those could develop more of a co‑ordinating role globally.

Chair

Can I follow that up? I am familiar with some of the work that goes on in the veterinary world, because one of the large veterinary schools, Leahurst, is in my constituency—Minister, you will always be welcome to visit. On the human health side, how do you ensure that you pull together the expertise that exists across the UK, particularly within academia and some of our research‑led hospital environments?

Professor Dame Sally Davies

We have different models, and we have not yet chosen the right one for this, but if you take dementia, another Government priority, what we did was fund competitively a number of centres and say, “If you win it, your research contracts will stipulate you are going to work together.” And they do: they have shared workshops, and they move trainees and techniques between them in order to make the sum of the parts greater than the separate bits. We have a number of models of collaboration and networks, and I think that out of the AMR research funders forum will come not only decisions about what needs supporting but, following the competitions to give that support, how they will need to work together.

Stephen Metcalfe

We have heard that the pipeline is blocked or broken and in need of repair. One of the reasons for that, potentially, is that the market itself is failing, that the incentives to develop new antibiotics are that you “pile it high and sell it cheap,” and you get your return on investment. But, of course, as you are piling it up, the resistance is building up. Actually, just for the record—because I think I heard David Tredinnick say that someone he had come across had decided not to use antibiotics, but to use an alternative first—can you just state that the resistance exists in the microbes and not in the human? It is the disease that becomes resistant to the treatment, not the individual. Is that correct?

Professor Dame Sally Davies

Absolutely true. The bacteria become resistant to the antibiotics, and it can be in a number of ways. One of them is little circles of DNA called plasmids that they can then pass to other bacteria, so, if I have resistant bacteria, those can be transmitted to the bacteria in my gut, for instance.

Stephen Metcalfe

Thank you for that. Going back to the market failure, how can we change the market so that there is more incentive for business to come forward and develop?

Professor Dame Sally Davies

This, as you know, is a very complex area and we have our analysts doing a lot of modelling of different ways of looking at it. In December, I led a forum on antimicrobial resistance that looked at this for the World Innovation summit for health. Essentially, it looks as if we will probably have to separate how you fund the development of antibiotics from how you pay for them, because, clearly, if we get an effective new antibiotic I, as chief medical officer, will want to say, “Never in animals. Just kill them if they’ve got it.” Meanwhile, I want to lock it up and only give it out to save lives. There are models where you can separate it; one that was used for vaccines was an advanced purchase initiative. What we have to find is not the right model for Britain but the right model globally, and then one, as we discussed earlier, that is not a one‑off that has to be replenished. My observation on these ways of doing things globally is that everyone is very excited up front and they put the money in, but the replenishment is hard work. We need a sustainable system. We are doing a lot of work on that and the Treasury is inputting on the analysis and the help as well, so this is truly cross‑Government.

Stephen Metcalfe

The Government are considering this as an alternative model.

Jane Ellison

Yes, very much so, particularly the point Sally makes about the need to co‑operate internationally because of the whole problem of market failure. The issue is being considered at various international forums, including Chatham House, the World Innovation health summit forum, and there are also discussions with regulators going on. One of the areas of work has been looking at regulatory processes and whether, if you can harmonise more of them, it is easier to co‑operate internationally.

Stephen Metcalfe

There is a recognition that the model needs to change.

Jane Ellison

Definitely.

Stephen Metcalfe

Is that the same with veterinary?

George Eustice

There is an added complication on the veterinary side, which is of course not just whether it is safe to use on the animal but whether it is safe then to enter the food chain. That is a further barrier and creates some uncertainties. Companies that develop these antibiotics potentially have the doubt that they could pour a lot of money into developing it only to find that, down the line, somebody says there is a health risk and it gets withdrawn, so they are left with the liability of that investment. I do not know if Peter wants to add to that, but there is the added complication on the veterinary side, which is that you have the food safety issue as well as the safety of the animal.

Professor Borriello

I think the anti‑infectives industry, whatever those anti‑infectives are, faces an additional problem compared with other medicines. They have to bear in mind the risk, even if it is working now, that, because their target might change, it will cease to work, which is unlike many other drugs. There is the added risk in recovering investment, plus competition from generics to help keep bills down in the health care sector. On top of that, peculiar to the veterinary side, is that they face the additional risk that, even if it is working very well and there is no resistance, it might still get banned on the precautionary principle because of the potential risk to humans.

Chair

Stephen, before you move on, David has a question.

Mr Heath

If I may. Just as a corollary to that on the veterinary side, Dame Sally now wants any animal that catches a disease to be killed rather than cured.

Professor Dame Sally Davies

No.

Mr Heath

I am parodying what you said.

Professor Dame Sally Davies

I recognise that.

Mr Heath

It is clear that there is going to be limited application, certainly of any antibiotics developed for human health reasons, in the veterinary world, which means that there is yet more emphasis likely to be put on preventatives—vaccination. Yet in the veterinary world, the commercial model for vaccination is also quite perilous. I am thinking back to Schmallenberg and the great big outcry, “What are we going to do about Schmallenberg? Develop a vaccine.” Unless it has changed, the take‑up of vaccine is relatively low, simply because the sums do not work out; for the average sheep, it is not worth vaccinating them against the risk of Schmallenberg coming across every few years. Is there a need to look again at the economic models for vaccine creation or formation, if we are to have a satisfactory solution for veterinary services?

George Eustice

I might ask Peter to come in on that specific one. The only thing I would say on the use of antibiotics in agriculture is that, as I said in my opening comments, there has not been the development so far of a lot of resistance. There have been, particularly with swine dysentery, I think three or four cases where resistance has built up and they have had to cull the herd. But, as a general rule, even some of the older antibiotics such as penicillin have been quite stable when used in agriculture, and they tend to be used, I think, in the veterinary world more sparingly than in the medical world. Coming back to my earlier point, some of the problems we have with antimicrobial resistance are happening because of the way they are used in the health sphere rather than the way they are used in the veterinary sphere. I do not know, Peter, whether you want to come back on the specific point around vaccines.

Professor Borriello

It is an important point, although we made light of it. There is an economic consideration, both in human and veterinary medicines; it is just that the barrier is much lower on the livestock side. You have QALYs—quality of life years gained, and so on—as part of the economic argument on the human side, but you do not quite get that on the animal side. As you said, the cost of administering a medicine to a sheep and continuing to feed it and what you will get at market, allied against not giving it the medicine and seeing if it will survive or killing it, is something that you would not consider on the human side. So there is that element. Market forces play a much bigger role on the veterinary side and it is a lower economic barrier, so there is yet another market disincentive to veterinary medicines compared with the human side.

Professor Dame Sally Davies

Could I pick up on the wonderful story about fish?

Professor Borriello

Yes.

Professor Dame Sally Davies

I am told that in America farmed salmon eat their weight in antibiotics, but in Europe they have individual fish vaccination, which started with one and I think it is now three different ones joined together, and antibiotic use has dropped to 2% of what it used to be. We do have success stories with vaccinations.

Professor Borriello

Yes, we do, and the major risk there is needlestick injury to the people who administer the vaccine. You are quite correct; currently, in the UK there is about 10 mg of antibiotic use per 1,000 kg of fish produced, so it is a very low ratio.

Stephen Metcalfe

Thank you. I have one final comment that I really wanted to make. As a dedicated free marketeer, it pains me to say this, but is this issue so important that we cannot just leave it to market forces to come forward and develop the next generation of antibiotics and on into the future, and we have to change that permanently?

Professor Dame Sally Davies

Sadly, you are right.

Stephen Metcalfe

Do the Government agree with that?

Jane Ellison

I think because of the need to co‑operate internationally, yes. It does not mean to say that the kind of innovation and everything that we associate with the free market cannot be brought to bear. That is why the chief medical officer and others are talking to a range of partners. It is not just in academia; there is a lot of engagement with industry as well. In terms of things like creating the size of market that will incentivise people to invest in this area, and harmonising regulatory structures to make it easier to work across borders, clearly, yes, there is an important role for Governments in co‑ordinating.

Stephen Metcalfe

Thank you.

Chair

There have been discussions inside the industry about decoupling sales volume from unit price. Are the Government willing to explore for new antibiotics some licence fee model within the NHS?

Jane Ellison

I have not considered that specific issue in any detail, but I think we are open-minded to all the things that might need to be considered to make sure that we can tackle this. I do not know if Sally wants to comment on that particular item.

Professor Dame Sally Davies

That is one of the mechanisms we are modelling and looking at the cost, but we could not do it on our own. We have to find the best mechanism for incentivising, but it is the public’s health, the public purse and what would work globally, so it is a complex area.

Chair

At the very least, you would need a pan‑European model.

Professor Dame Sally Davies

At the very least.

Chair

And probably even a bigger market, perhaps bringing in north America as well.

Jane Ellison

There has already been work between the EU and the US. I think they have recently clarified guidance for clinical studies for products, again to try and get harmonisation, to make it easier to make progress.

Pamela Nash

Could the Minister clarify for the Committee, following the restructure of the NHS, exactly where responsibility lies with the various bodies now in the health care system that relate to AMR?

Jane Ellison

The first point I would make is that the new strategy is contemporaneous with the new structures within the NHS. While in some areas there has been more challenge around, if you like, working things across, the new strategy has been set up in the knowledge of the new architecture of the NHS. You obviously have NICE setting some kind of clear governance guidelines and PHE are very much in the surveillance, bearing in mind that they are the successor organisation to the Health Protection Agency. PHE have an important surveillance role, as well as some practical delivery roles around things like developing tools. They have done work, for example, developing things that could be used in care homes to help people, as well as throughout the NHS. There is a clear leadership role from the Department of Health, which you can see through the work we are doing on co‑ordinating leadership, research and all of those things. Obviously NHS England has a huge implementation role, as well as looking at how they drive that through primary and secondary care. All of those groups sit on the high‑level steering group.

Pamela Nash

Are you happy that those roles are very clearly defined for each of those organisations?

Jane Ellison

Yes. As I said, the high‑level steering group has been brought together in the new NHS architecture, so in that sense it does not have some of the kind of undoubted challenges in other areas where you are trying to take something from where it used to sit and to sit it somewhere else. The new strategy has been designed in the knowledge that we started with those organisations. I should have mentioned Health Education England too, with their role around education and training, and making sure that AMR is hard‑wired through that. They all sit on that. The strategy is new, and it clearly is going to go through revisions. We are going to make sure it responds to this Committee’s findings, for example, in terms of looking at the metrics and the action plan. I think people are clear, and we have so many opportunities now because we are going to have regular updates and reviews, and the high‑level steering group meets to look at all these things. Where there is lack of clarity—if the Committee, for example, feels in your report that some of those areas need clarification—we are in a position to respond to that rapidly.

Pamela Nash

I was going to ask you to respond to Imperial college’s criticism that the UK AMR strategy does not incorporate “fully the wider changes to the NHS and public health structure.” Do you think that is a fair criticism, and that it could be improved?

Jane Ellison

I probably need to look at the detail of exactly what they said, which I have not had a chance to do. I would be very happy to look at that; again it is something that we can refer into—

Pamela Nash

Just to be clear, it is in the written evidence to the Committee.

Jane Ellison

I have not had a chance to look at the detail of it. That may well be a fair point to make—it is a new system which is settling down—but I think it presupposes that there was high‑level attention to this subject in the old NHS architecture, and I do not think there was. I think we have gone up a complete gear now in terms of where we are. For that reason, I think we are quite front-foot, but we will look at all of those points and see if we think there needs to be clarification. One point I would make is that, if you do not have everyone involved, you do not get that level of cross‑system buy‑in. Another point I would make, because this often comes up in discussion of the old and the new NHS architecture, is that just because it might have looked like a simpler system under the old NHS architecture, it did not mean it was any less a complex and difficult‑to‑influence organisation. This is a big, complex health economy, and it would always be difficult to drive change across such a big organisation. I think there is greater clarity around some of the roles—for example, Public Health England—and we will continue to work with them to get clarity around their role across a range of things, including this, but actually I think there are opportunities, as well as the obvious challenges, in the changes.

Pamela Nash

The Government have concentrated on speaking about the benefits of localism, in terms of the NHS restructuring, and devolving power down. Something like antimicrobial resistance clearly needs a national response, and indeed an international response in this case. Do you not think that now it will be much more difficult to have a centrally pushed strategy against antimicrobial resistance? How much control can the UK Government have centrally over how we fight this across the country?

Jane Ellison

The leadership is central. The leadership is coming from the top; it is coming from central Government. NHS England sits on the high‑level steering group, so they are driving it across the NHS. On the extent to which health care is localised, where for example, we might want to see local systems responding, clearly we want to see CCGs responding to the leadership and guidance they get, and we would want to see local authorities in their role with care providers, and their own role as a care provider, drive best practice. But in terms of where the leadership is coming from, where the targets are being set, driving things through joint strategic needs assessments, that leadership is coming from the top, and I do not think there is any sense in which central Government feel this is something that we are going to just let happen or not happen at a local level. It is too important for that. Actually, although there is a great deal of localism about the way we deliver health, the architecture, in terms of setting the strategy through things like the mandate, remains something that we drive from the centre in terms of setting national standards.

Pamela Nash

I have one last short question, Minister. It is clear that you have political responsibility for this in Government, but, under you, who has civil responsibility ultimately for AMR?

Jane Ellison

I am sorry, I did not catch your question.

Pamela Nash

Who has responsibility in the Department of Health for this?

Jane Ellison

For AMR?

Pamela Nash

Yes.

Jane Ellison

It sits in my portfolio, but ultimately—

Pamela Nash

I mean in terms of staff, the civil servants.

Jane Ellison

It is led by the chief medical officer.

Pamela Nash

Thank you.

Chair

I want to pursue this line slightly, because we have heard—not just in this inquiry but in other exchanges in Parliament—that organisations like the ABPI are expressing concern about the management of, for example, clinical trials. We know there is the new research agency which is supposed to be addressing some of those things, but things are happening around us. We have just had the closure of Novartis at Horsham, for example; they have pulled their research out of the UK, full stop. That cannot be good for UK plc, both in terms of the health of our nation and the economy of our nation. One of the reasons they cite is the issues around clinical trials, the lack of central direction in managing research programmes. Yet at this stage, in response to my earlier observation, you appear only to be just beginning to look at things like new models of economy for driving drugs into the market. Is there enough work going on in this area? Is there not a huge gap there? We are losing some of our research expertise on the one hand and, on the other, we have market failures, which you acknowledged to Stephen Metcalfe—a problem that is extremely serious. Isn’t it time to think of a different approach rather than simply relying on, “The new structure will deliver”?

Jane Ellison

Do you mean on research?

Chair

I mean in all respects. How are you going to manage new clinical trials, for example, in the new structure? How is that going to happen? How are we going to ensure that there is, taking Pamela Nash’s point, some central direction in prescribing to ensure that there is a consistent approach? How is that going to be led from the centre in the new structure?

Professor Dame Sally Davies

Let me start with the research because I hold that responsibility from Ministers, for the clinical and applied part, through the National Institute of Health Research—the NIHR. Actually, the NIHR has not changed as the system changed, because what the NIHR does is provide a fully‑funded infrastructure to the NHS regardless of how it is constituted. Indeed, when they are non‑public providers of services we can even, through our managed clinical research networks, support research in non‑public sector providers. I think if companies are saying that they are withdrawing because the clinical research environment is not good enough, they are not looking at the metrics. For instance, a very important metric to them is global first patients in clinical trials. This year so far we have had 25 in England, last year 12, the year before two, and before that none. Putting in the managed clinical networks has absolutely changed delivery in clinical trials to time and target. They are working with the NHS, whatever its management structure. NIHR both funds some research, as your membership has brought up, and co‑ordinates infrastructure. We work very closely with industry, because we are the arm of the Department that has to work directly around the economic investment and growth area, so we are concerned about disinvestment. On this occasion, I want to highlight how concerned I am that AstraZeneca has closed down its Bangalore site, which was on anti‑infectives, and is downsizing its anti‑infection group—or its infection group—as it moves from Alderley Edge to Cambridge. This is worrying not just for Britain but for the world in the production of new antibiotics; but it is not because we do not have an organised, supportive clinical research system.

George Eustice

That links back to the point that Mr Metcalfe made earlier. Like him, as somebody who believes in free markets, I am reluctant to abandon the concept that we should encourage private enterprise to fund these things. Another element is having regulatory certainty and consistency, so that companies that make an application for a patent know that they are going to get that patent protected properly and things are not going to change in a few years’ time. The EU veterinary medicines directive is currently being reviewed and we are waiting to see what comes back from that. But I think that having something that could extend data and patent protection might strengthen the incentives for private companies to do more research to find new antibiotics.

Chair

In general, it seems easier to effect change in the veterinary world. Is there an underlying reason for that? The patients do not complain as much perhaps?

George Eustice

Perhaps the patients do not argue. I do not know. Peter?

Professor Borriello

I cannot comment on that because I do not know whether that is true or not.

Chair

But you have been able to affect prescribing practice more. In earlier answers, you explained that fewer antibiotics are used in our animal population than, I think, in many other countries. That is a combination of things. I see it in other areas of agriculture—for example, in the use of agrochemicals. Many of the manufacturing companies work very closely with farmers in testing products and making sure that overuse does not occur. That also seems to happen in the veterinary medicine world, but there is not the same effect coming out on the human side. Is there something special happening in veterinary science that we ought to learn from?

Professor Borriello

Coming back to your original question about fragmentation and having uniform responsiveness from various bodies, the veterinary field has both advantages and disadvantages from this fragmentation. We do not just have lots of different types of animals; we also have lots of different types of animal sector. Even with cattle, you have dairy cattle and beef cattle. There is not an NHS equivalent. They are all independent, including the general practice equivalent, which is local veterinary practices, for small animals. We already have that fragmentation, which makes it difficult to have a single lever. But contrary to that, because there are discrete sectors, it means that you can look at sectors in almost bite‑sized chunks, and they do work together very closely; they have to, because it is about produce, particularly on the livestock side. There are advantages and disadvantages to fragmentation. It would be lovely to claim that the advice, the newer prescription guidelines and the tight regulations from Europe are the cause of better regulation, better use and less resistance. Actually, I do not know the reason why there appears to be less resistance in veterinary pathogens. It could be by chance.

Chair

This leads me to where I was going, back to the Department of Health. Are you prepared to amend health care‑associated infection targets, should they prove to drive greater use of critically important antibiotics?

Professor Dame Sally Davies

We are advised by ARHAI, as I said—our specialist expert advisory committee. If they believe that we should be collecting different metrics or changing the mandated collections because it is impacting out there on practice and making it change for the worse, then the Government would do so.

Chair

What advice have you received from your scientific advisers on the efficiency of HCAI targets?

Professor Dame Sally Davies

I have seen the dramatic impact that having targets has made and I know that there is some rising concern about the issue of, “Is it pushing an increase in carbapenem use?” We are seeing increased carbapenemase‑producing enterobacteriaceae. That is worrying, but we have not, that I am aware of, had formal advice that this should change at this point, but that is exactly why we have an overarching steering group and a scientific committee so that they can advise us on metrics. You heard my view that I would like a broader collection of metrics. I am not sure we should give those up—because it is for the experts to tell us—and I would personally like to see them as mandatory. The scientists will need to make the case to Government because then the CQC will be able to use them and inspect and help us drive up performance.

Jane Ellison

We are aware that we need to look at the need to move away from some specific indicators to a more comprehensive approach. We are very much open to that.

David Tredinnick

I would like to return to limiting the use of antibiotics for animals. Twenty-six years ago, in the House of Commons Chamber, I raised the issue of feeding antibiotics to chickens in Indonesia. I was not the only Member at the time to be concerned about the misuse of antibiotics. Rolling the clock forward, my understanding is that we now have a situation where the European Union may legislate to ban the use of antibiotics in animals altogether. Have you been involved in those conversations, Minister?

George Eustice

If you are talking about the use of antibiotics preventatively, my understanding is that farmers, even if they are using those antibiotics in feedstuffs, still need them to be prescribed by their vet. The protection is the same, and I think some progress has been made in reducing that. In terms of banning it altogether, I might ask Peter to come in on that because I am not aware that the EU is talking about banning it altogether, but the central point is right: they should still be prescribed by the vet based on the evidence on the farm. There are cases where, for instance, if you have some of the bugs that cause diarrhoea in piglets and things like that, the ability to have it administered through the feed to that herd of pigs is more effective than trying to manually vaccinate them all. I do not think you would want to remove it as an option, but you are right: where it is used we have to make sure that it is done the right way round, that the vet linked to the farm actually prescribes that as an approach rather than—this is where there are some concerns—a situation where a feed company says, “We can do this. Just get your vet to sign off a bit of paper.” We need to make sure that the controls are right, but we would not want to remove it as an option. Is that right, Peter? Is there anything to add?

Professor Borriello

Yes. Briefly, there is no indication whatsoever that the Commission intends to ban all antibiotics for animal use. That would be contrary to the animal health and welfare regulations anyway. There is an indication that they wish to have greater control on antibiotics that might be used in a preventative way. They are used in a preventative way both on the human and the animal side in a number of different ways. Our personal view for the UK is that any preventative use as a substitute for good animal husbandry should be banned. It is as simple as that—preventative use, to prevent disease, just as it would be for the case of a child with meningitis in a school, where you might treat her close contacts and her classmates. The same is true on the veterinary side, irrespective.

Chair

Can you cite an example of where antibiotics have been used in place of good husbandry?

Professor Borriello

I cannot cite a particular example, but there is the view held by many that improved biosecurity, which is the animal side equivalent to infection control on the human side, may reduce the need for some of the preventative use. There is a view that in some cases it could be that they are being administered because they are needed, but they would not have been needed if there had been better biosecurity. All those aspects are looked at as part of the process of improving animal management in the livestock industry.

George Eustice

There was some progress made in 2006 when the routine use of antibiotic growth promoters in some foods was banned at that point. That was precisely because there were concerns around antimicrobial resistance building up.

David Tredinnick

Are you aware of the European Union agriculture committee amendment to the 2012 budget, which has allocated €500,000 for funding of research into homeopathy and herbal medicine in livestock farming as an alternative to the use of antibiotics, and do you support research into alternatives in this way?

George Eustice

I did look into this and there was a fund—I think you are right—of around €500,000 that was set up in October 2011 to look at this. It has now been subsumed into a more general budget, but which is to look at alternatives to the use of antibiotics. Yes, obviously we support that. As I said, in the VMD’s own research—the six projects it is looking at—two of them have elements of some of these things, preventative measures other than just the straight use of antibiotics. One of those is looking at the drivers behind the use of antibiotics and whether alternative approaches could reduce it.

David Tredinnick

Could I finish on this, Chair, if I may? Having looked at this field over the last 25 years in both people and animals, I suggest to you that there is a way of reducing antibiotic consumption by making greater use of people like Hydes Herbal Clinic in Leicester or going to doctors who are qualified as homeopaths. They have been qualified by Act of Parliament since 1950; it went through the House unopposed—I checked yesterday—so it was not controversial at the time. If we embrace these alternatives, there is a way of reducing demand for antibiotics, and I would suggest to you that, in the face of the huge obstacles in creating new antibiotics, this has to be part of the package.

George Eustice

Okay, I know you have been a long‑standing advocate of these approaches, and all I can say is that we support, obviously, the fact that the European Commission has allocated some budget to that, albeit that I think it has now gone into a slightly broader budget, to look at a broader sphere of things, including whether we can mitigate or reduce the use of antibiotics. But I fully take on board your point. As I said, there are elements of what you are asking for in two of the projects that the VMD is doing.

Chair

In terms of the allocation of such budgets, how would you expect research programmes to be designed?

George Eustice

I would expect Peter to design them. The six of them that I have in front of me look very thorough but are part of a trans‑EU collaborative project, as I said earlier, so there is other work being done in other countries of the EU so that we do not duplicate our effort.

Professor Borriello

My only comment would be that with respect to scientific process, which has stood us in great stead for a long time—going back to the era of the Greeks; the scientific process has been with us for a long time—particularly for medicines, there is no such thing as alternative. Everything is considered and everything has to go through the same rigorous process. A key element of the scientific process is not to try to prove something, but to try to disprove it. The more rigorously it stands up to attempts to disprove, with appropriate controls, the more certainty you have in the findings of the conclusions. We have no prohibition, and there is no prohibition, on anything coming forward for a marketing authorisation for a medicine as long as it meets the accepted criteria for proven efficacy, safety and, in the animal field, not just safety to the animal, but also safety to the environment and to humans. On that basis, there is no prohibition. Equally, we do not hypothecate research to particular areas. We would have an open call for certain research areas through research councils.

Professor Dame Sally Davies

I want to make sure that we do not lose sight of the fact that some people are very sick with bacteria; they need antibiotics and there is no alternative. What we are talking about is trying to limit the use of antibiotics, or stop their inappropriate use in order to conserve them, and indeed globally not only conserving what we have, but actually trying to increase their availability to people who need them. I think alternatives may come in for prevention—clearly vaccination is very important. However, we must never lose sight of the fact—this is one of the reasons I am so concerned about antimicrobial resistance—that there are people, probably about 5,000 a year in England, dying of resistant E. coli infections, for instance, and they needed antibiotics and nothing else would have worked.

Stephen Metcalfe

I want to go back to something I was asking about earlier, diagnostics, but also to build on Graham’s questioning about centres of excellence and the focus for research. We now have a series of Catapult centres. There has been talk about creating a Catapult centre for diagnostics and stratified medicine. Now I think it has been slightly renamed as a precision medicine Catapult centre. Do you think there is a role for that, and is it something that the Government would support?

Professor Dame Sally Davies

By definition, the TSB is an arm of Government; it is an ALB in part of the BIS family of research councils. I am interested in how precision medicine, or stratified medicine, will get us to where we need to be on rapid diagnostics for AMR. I think it could, but most people when they hear “precision medicine” and “stratified medicine” think first and foremost about cancer and cancer drugs. My concern is: will they, if they fund it as “precision medicine,” then end up supporting just cancer and therapeutics like that, or will they help where we need it in rapid diagnostics for AMR?

Jane Ellison

We very much recognise that developing new diagnostic techniques is a big part of how we respond to this challenge, not just developing them but obviously then seeing how they would be used.

Stephen Metcalfe

Do you think the change of name to “precision medicine” rather than “diagnostics and stratified medicine” is not terribly helpful in actually making clear what we want to come out of this Catapult?

Professor Dame Sally Davies

I felt I needed an explanation, but maybe people in the field do not.

Stephen Metcalfe

I am sure that will be noted. Thank you for that. BIVDA have commented that there are good diagnostic tests available—not enough perhaps, but there are some good ones—but they are not used to their full extent here in the UK. We have heard elsewhere on other inquiries that the NHS, as our main health provider, can be very slow to adapt to change, for various reasons. If we are to develop new diagnostic tests, how do we ensure that they get taken up?

Jane Ellison

That is certainly one of the reasons why NHS England is a critical member of the steering group; we are aware of that challenge. I know that this is something that is being looked at. Partly it is about things like making sure there is NICE guidance, and partly it is about removing perverse incentives that might exist in the system that would stop people using a rapid diagnostic. I do not know if Sally can comment any further about the detail of how we are addressing this.

Professor Dame Sally Davies

As I said earlier, if people produce a really good cheap one, we will not have a problem. BIVDA actually cover in vitro diagnostics. It is always nice to have better equipment in the lab, but that is all working all right; what we need is cheap point of care, and, while the technologies exist, I am told they have not been put together into the cheap rapid diagnostic we need.

Stephen Metcalfe

You may well be right, but it is not quite that that I am disputing. It is the ability for the NHS to adapt to change rapidly enough to adopt something new. We heard—as I said, on another inquiry—about something that might help remove prions from surgical instruments, but it was not taken up because it was very difficult to get the NHS to fit in that extra process. That is in the public domain because we heard it at an open inquiry, but it was an example of that inability perhaps to adapt its systems.

Professor Dame Sally Davies

I think you and I will be discussing that at the end of April, so I will leave that debate for then. This is quite different from prions. This is something that touches every single person, and they know it does. We are getting through to even, I discovered, the London taxi driver, with one telling me that I might not need antibiotics for a cough. I think that if we can get a good, effective rapid diagnostic on this one—it has to be specific and precise and all of those things—I do not foresee the same problems. Doctors, and doctors are key in this, embrace new technologies if they know there is a problem and they can see it will help. This is an area where there is growing recognition of the magnitude of the problem, the severity of the problem and the need to change. This will be one area where we can make a difference.

Jane Ellison

Of course we want to try to get this area embedded in the mandate as well, which will give it that absolutely system‑leading importance. Work is under way on that. Mr Miller, earlier I think I misunderstood Pamela Nash’s question about who leads in the Department. For the record, it is worth saying that our senior responsible officer in DH is the director‑general for public health, and she reports on progress in this area to the executive board.

Chair

Thank you very much.

George Eustice

Can I add something on the rapid diagnostics? I know it is more pertinent to the NHS, but we are aware that there is some research being done in the private sector on veterinary rapid diagnostics as well. It is generally termed “pen‑side diagnostics,” for reasons I do not understand, but there is an incentive, if we can get it right, for vets to want to go down that route, because at the moment you have a delay, sometimes of several days, before being able to get the diagnosis and prescribe the right drug. If you could get a reliable enough diagnostic, there would be an incentive for it, and a commercial incentive as well for farmers to be able to act early to deal with problems.

Professor Dame Sally Davies

Not only are we working towards the next NHS England mandate in November, but we have asked them in their discussions with GPs about the new GP contract to make sure that AMR is properly reflected in their contract. That is a discussion with the BMA, but they are doing their best.

Professor Borriello

For both the human and the veterinary side, there is the issue of whether you are talking about quicker diagnostics or rapid diagnostics. Certainly the NHS has adopted some very innovative new technology—the so‑called MALDI‑TOF: mass spectrometry for identifying germs. It works and it is being adopted quickly. The problem with trying to get near‑patient or pen‑side is that it means you take it out of the hospital and into the community setting, and there you have the whole problem of, “Is it the right sample for that particular diagnostic? Is the price right? Can it be read properly? What is the quality control?” By and large, if you are going to influence treatment for infections, rapid can only mean one thing—immediate—otherwise you will go with best, appropriate and empirical, and wait for your diagnostic to inform you whether or not you need to change it.

Stephen Metcalfe

Thank you very much.

Chair

We have covered a huge amount of ground this morning and I am sure there are a few additional bits that might be fed in. Please feel free in the next few days, if there are additional comments you would like to make, to submit further evidence. In the meantime, two Ministers and two professors, thank you very much for your time this morning. Oral evidence: Antimicrobial resistance, HC 848 28