Oral evidence: Antimicrobial resistance (AMR), HC 848Wednesday 8 January 2014

Oral evidence, 8 January 2014.

Witnesses

John Hardcastle, Chief Executive Officer, Novolytics, Dr David McIntosh, Global Scientific Affairs Senior Expert, Novartis, Professor George Lewith, Professor of Health Research, University of Southampton Medical School, and Doris-Ann Williams, Chief Executive, British In Vitro Diagnostics Association, gave evidence.

Chair

Thank you very much for attending this morning. It would be helpful if you could introduce yourselves.

Doris-Ann Williams

I am Doris‑Ann Williams. I am chief executive of the British In Vitro Diagnostics Association, the industry association representing manufacturers and distributors of diagnostic products in the UK.

Professor Lewith

I am George Lewith. I am a professor in the department of primary care. I work very closely with Mike Moore on a number of studies, which David Tredinnick just mentioned. I am a GP and a consultant physician. I have 30 years of experience in researching herbal medicines and hold a variety of roles. One of the things I have been involved with very recently is getting the National School for Primary Care Research—part of the NIHR—to develop a really powerful working group looking at alternatives to antibiotic prescribing both in care homes and in primary care, using a variety of nutritional and herbal approaches, particularly in relation to urinary and lower respiratory tract infections. I do not represent anybody other than the University of Southampton and the NIHR.

Dr McIntosh

I am David McIntosh. I am a paediatric infectious disease specialist. I am also an honorary clinical senior lecturer at Imperial College in London. I act as the global scientific affairs senior expert for Novartis Vaccines, and I teach at a number of universities around the world.

John Hardcastle

I am John Hardcastle. I am the chief executive of Novolytics, which is an SME company in Daresbury; we research into bacteriophage therapeutics. Prior to that, most of my career has been spent in the venture capital industry.

Chair

In different ways, you all propose alternatives to antibiotics. Could you each outline what your approach is? Let us go down the line again.

Doris-Ann Williams

The diagnostics industry sees the tools that our products produce as a way of appropriately differentiating patients’ treatment. In primary care there are simple tests, as we heard in the last session, which are in common use in the Nordic countries, Germany and Switzerland and also in the USA, to differentiate between viral and bacterial infections, and allow a debate or a discussion between the primary care physician and the patient as to whether an antibiotic is appropriate for that condition or not. In secondary care, it is a way of targeting antibiotic therapy to make sure that the correct antibiotic is used for the correct infection. Increasingly, there are products available that will look at more than one parameter in one sample type, and they are reducing the length of time to get the results. In the traditional microbiology lab, it would take five to 14 days to culture up micro‑organisms; you can now do it within five hours using molecular technology.

Professor Lewith

My background is as a clinician, a GP, so I can add to some of the comments made by Dr Moore and I can certainly expand any that may be relevant to this part of the meeting. As a primary care physician, you are in a very difficult position; you are in a one‑to‑one situation with a patient who may want or demand an antibiotic. Education works to a point, and we discussed the strategies in the previous part of the meeting, but GPs very much feel they need alternatives. The evidence we have from the research is that they would look at things like herbal and nutritional medicines if they were thoughtfully evidence based. Within the EU, particularly in Germany, 20% of the OTC prescriptions are for herbal medicines. There is a real good track record of herbal medicines being better produced and us getting better quality herbal medicines in the UK, and better herbal practitioners, particularly since the 2001 House of Lords report. My main approach would be to try and see how we can use these kinds of approaches, looking at good science but perhaps understanding that we are not after a magic single chemical. Herbals work differently. They work synergistically and often through several different immuno‑modifying mechanisms. One herbal, which may have 40 or 50 different biologically active chemicals, may be working through several different systems, and nutritionals may be as well. They modify many different systems in the body, so it is a different kind of approach, which requires a slightly different understanding of science. I think we can use those approaches to manage symptoms and mitigate antibiotic prescribing in primary care very effectively when we know that there is good preliminary evidence and we do not need to make many of the antibiotic prescriptions that we are making.

Chair

Thank you. We are going to pursue that a little further later on.

Dr McIntosh

Antibiotics are used for treatment generally, and vaccines are used for prevention. We have had a golden age of antibiotic development, and I believe that golden age is coming to an end. I believe we are at the beginning of a golden age of vaccination and discovery of vaccines. Vaccination has the potential to prevent patients from being admitted to hospital, thereby preventing their exposure to organisms in the hospital. Vaccination also has the potential to prevent disease in the community; in fact, vaccination can prevent large epidemics. Vaccination can prevent the long‑term consequences and sequelae of infections. I believe that vaccination is now the best approach for looking at organisms, both resistant and multi‑resistant and susceptible in that fashion, by targeting multiple targets on these organisms. Antibiotics just target one aspect of the organism. Vaccines have the potential to target multiple targets on the organism. I also believe that with effective vaccines against community and healthcare‑associated pathogens, and effective implementation, we have the potential to reduce antibiotic resistance by up to 50%.

John Hardcastle

We are trying to develop bacteriophage therapeutics. Phages are viruses that kill bacteria, and you will be drinking them as you drink your water. They have been around for longer than bacteria. They are used regularly in the eastern bloc, but they are not used here yet because we have not done clinical trials that are to western standards. Our belief is that they will form a complementary approach to the use of antibiotics. They are very narrow spectrum. Typically, any one phage will only kill a number of strains within a bacterial species, so you need to know what bug you are dealing with before they are effective.

Chair

That response, from your point of view, answers one of my next questions: are other countries ahead in your particular fields and are the procedures for adopting alternatives in the NHS easy ones to deal with?

Dr McIntosh

With vaccination, the United Kingdom has set an extraordinary example over many years of introducing new, innovative vaccines. We have now not completely conquered, but are getting towards conquering, the great killers of the 20th century, and before that. We now face somewhat rarer infections in the community, such as meningococcal infection, and in the hospital, such as Staph and E.coli. With its extraordinary track record of vaccination, the United Kingdom is in fact right at the sharp end of being able to develop new vaccines. Of course, other countries are using various vaccines, and the United Kingdom is using those and other vaccines, so it does depend somewhat, but my point is that the United Kingdom is really very advanced with the implementation of most vaccines.

Professor Lewith

My response is that you need all of us in a co-ordinated way. You need phages when you have really bad infections in hospital. You need vaccinations for prevention. You need simple primary care approaches that stop over-prescription and you need near‑patient testing, so you need the technology. You need to implement the near‑patient testing by making private contractors in general practice do it so that it is feasible, so that they do not lose money. At the moment, they would be paying for the tests themselves out of their own wages. You need better research for symptom‑relieving remedies, and we need a better structure to manage that research within the NIHR. We need the vaccinations preventatively, and we need better strategies when we have serious overwhelming infections in secondary and tertiary care environments. You cannot have one of us without the other. I am sorry I am in the middle. I am the GP, you see, and I am always in the middle.

Doris-Ann Williams

I agree that we are not talking about one of our approaches against all of them. There is room for everything to fit into the health care picture. One of the problems, which George just alluded to, was the cost of doing testing in primary care. It is an added cost, but there are ways around it. Outside of antimicrobial infection, GPs have started doing simple tests, which stop referring to secondary care, and the money is recouped in other ways. Companies are quite innovative at doing risk‑sharing projects on costing, so I do not think that is beyond the wit of us to do. Much more important, I think, is awareness among GPs of what tests are available commonly and are being used in northern Europe and in the US.

Stephen Mosley

I wanted to discuss vaccinations in particular, so I guess this is mainly aimed at Dr McIntosh, but if anyone has any comments, please add in. In your initial answer, you covered the broad areas and I want to be a bit more specific. We have had recent news in the London press about TB and the incidence, or rates, of TB in London in particular. The current TB vaccinations that we all had as teenagers are 70 years old now. I think you said that we are entering a golden age of vaccination. How can that be so when the vaccines are so old?

Dr McIntosh

Of course, we have had an unfortunate failure of the development of a new tuberculosis vaccine from the Jenner Institute, and this was sad because we do need to replace the BCG vaccine for tuberculosis. The approach that has been used for the Bexsero meningococcal serogroup B vaccine is called reverse vaccinology, and this is what I mean by a new golden age of vaccine development. By looking at the genetics of the organism, we now have the potential to identify targets that can be used for vaccine. The serogroup B meningococcal vaccine—the Novartis Bexsero vaccine—was developed along those lines. For the nosocomial infections—to be specific, Staphylococcus aureus—there has also been a failure, or two failures, of vaccines. E.coli, Acinetobacter, Enterobacteriaceae, Klebsiella and so on: we need to use this new sort of technology to develop specific vaccines for Staph, E.coli, Staph epi and so on. When I say golden age, we are going to have great difficulties in developing new antibiotics unless there are some miracles. But we have the potential now to use genetics, looking at these very resistant organisms, to develop vaccines, not necessarily to use them throughout the whole community for everyone, like we generally do, but to use these new vaccines in a more targeted approach, especially for people going into hospitals, people who are at risk of these serious infections.

Stephen Mosley

Is one of the problems you face—going back to the BCG—that it only protects against certain strains of the TB virus, or bacteria? Is there a problem that, if you are just vaccinating against certain strains, actually you can encourage the other strains to develop?

Dr McIntosh

The beauty of this new approach is that one can attack or prevent as many potential strains as possible, and again I refer to the meningococcal serogroup B. Until now we have had a vaccine in Córdoba, a vaccine in Normandy and a vaccine in New Zealand, because that is where there have been particular strains of this organism. But in fact there are hundreds of different strains of this organism around the world, the meningococcal B, and now we have the potential to have a vaccine which can cover the majority of those strains. Similarly with Staph, similarly with tuberculosis; in fact, what I would also like to mention—this might come as a surprise to you—is the role of viral vaccines in preventing antibiotic consumption and antibiotic resistance. For example, influenza may result in secondary super-infection, bacterial infection, and this is why the influenza vaccine has the potential to prevent antibiotic usage. I think we should be talking about bacterial vaccines and about viral vaccines as well.

Stephen Mosley

Why is vaccine development so much behind antibiotic development? Again with TB, it is 70 years since it was developed. There must be some sort of failure in the system.

Dr McIntosh

With vaccine development we have been using, let’s call them, old‑fashioned approaches, mushing up the organism or breaking up the organism, using bits of the organism, intuitively trying them out. Now we have the potential to look at the genetics of the organism, do various tests after that, using bioinformatics and computer systems, and really identify the targets that will be successful vaccine targets.

Stephen Mosley

Why hasn’t that come along in the past? Is it a technology thing or is it because of the market situation? Drugs companies have a vaccine on the market, it does 90% of the job, so, hey, it is not really worth their economically developing a new vaccine. Is that the case?

Dr McIntosh

No.

Stephen Mosley

Why has it taken 70 years?

Dr McIntosh

It is a long process to develop a new antibiotic. It is also a long process to develop a new vaccine. It is very expensive. Once you have done that particular process of discovery of an antibiotic or a vaccine, then you have to run it through human clinical trials, you have to get it approved and so on, so it is very costly. I think that the process of reverse vaccinology will reduce the costs of developing new vaccines. I do not see any new techniques available for developing new antibiotics. I think the discovery process there is fixed. We now have a flexible, new approach to developing new vaccines.

David Morris

Ms Williams, you said you wanted Government action to ensure existing diagnoses were taken up more widely in the NHS. Is there ready evidence that this would be cost‑effective?

Doris-Ann Williams

There is some evidence. There are studies done on certain tests. There are international audits; there is an audit on a C‑reactive protein, which is a test to show rise in infection. There are some studies, with cost‑effectiveness related, available from a global study. Cost savings within the NHS are hard. There is never a bag of cash that is released. With diagnostics, it is more that you are shifting resources to be used elsewhere, or releasing capacity, much more than actually turning up with money at the chief executive’s door, and it is quite hard to track that through the system. It is not quite as clear; it is not as simple as taking a pill and someone gets better, or they don’t, and they release a bed. Diagnostic tests produce information which is used, but it is only one step in the pathway. It is quite complex.

Professor Lewith

If we use a CRP, which is C‑reactive protein, you can use it as a near‑bedside test. That is what GPs can use. It is reasonably effective at differentiating between viruses and bacteria. It is something that is used outside the UK quite widely. We do not use it here, as I said, because it costs the GPs three quid each time they do it, and they might be spending a lot of three quids in a winter. We are about to pilot a large study in Southampton—Mike Moore is running that. It will be piloted through our clerk and we will look at the cost‑effectiveness of offering that remuneration within primary care. That is a process that is in the planning stages at the moment. It is a very good question, and it is one we need to answer for the NHS, but we need rigorous evidence, which we do not have yet.

Dr McIntosh

There is great potential for synergy between diagnostics and vaccination. I refer to the previous session in terms of the fear of medical practitioners that the patient could have some underlying serious infection, and therefore the wish to prescribe antibiotics. With diagnostics and successful vaccination, we can reduce the fear level—not only in the medical practitioners but also in the public—that the patient will have a severe infection. I think there is a great potential for synergy between diagnostics and vaccination. We mentioned influenza diagnostics. We should mention the great success of the pneumococcal conjugate vaccine, which has really reduced the fear of people having pneumonia, because it has reduced pneumococcal pneumonia, and the great success obviously of measles, mumps and rubella, measles being associated with pneumonia as well. The synergy between effective diagnostics and effective vaccination can certainly impact on compliance, the number of prescriptions, the fear of patients that there is a serious infection and also on this public debate about whether or not antibiotics should be used.

Professor Lewith

David, I agree with you that it could impact, but it is not, because it is not getting into primary care. It is not happening. The science is right, but the dissemination and the activity are not happening from the GP’s seat. We have real issues—Mike Moore and some of the other guys were talking about it this morning—about a co-ordinated process of making this happen in primary care where the prescriptions are happening.

David Morris

Presumably information on the incidence of infection and resistance would be useful to companies producing diagnostic tools. Should these companies be doing more to facilitate gathering the information, to aid their product’s production?

Doris-Ann Williams

Access to that sort of information is quite tricky. As an industry, we are small with limited resources, and it is a bit of a vicious circle to drive production of a product when you have limited resources to pay for the data and the information. But companies are quite happy to work in combination with the NHS wherever possible to produce that sort of data.

David Tredinnick

This is really to Mr Hardcastle and Professor Lewith first and foremost. What advantages do your approaches have over other traditional antimicrobials?

John Hardcastle

The thing that gets me about this discussion is that there is lots of talk about “potential”, and the thing that Dame Sally Davies keeps emphasising is that we are running out of time. The critical thing for us is that we know that phages work; it is just that we cannot make them available in this country. The reason we cannot make them available in this country is that we have more rigorous regulatory standards. First, we know that there is evidence that they work. Secondly, they are harmless in man and they are inert; therefore, the rate at which you can bring them through the regulatory regime should be quicker. Thirdly, there are lots of them. One of the issues that the antibiotic development arena has is that there are lots of possible candidates and very few of them actually get through to being useful drugs. From our perspective, we have a lot of good putative candidates already.

Professor Lewith

I think that the nutritional and herbal approaches have some preliminary evidence behind them. We need some further investment in research, so we need some harder studies to demonstrate that they really do control symptoms, and that they can be prescribed by GPs, or over the counter and made available by pharmacists, so that the GPs can feel they are doing something. It is very difficult when somebody comes to ask you for help to say, “Go away and put up with it for five days.” We do not have that kind of culture. We need to be able to do something that is safe and does not actually load up antimicrobial resistance for the future. There is huge potential with herbal remedies, but I think we need to move away a little bit from the drug‑mining element of herbal remedies, where we are looking for the wonderful chemical in the way they looked for the new malarial with Artemisia. We need to see them in a slightly different context, as more complex mixtures of chemicals. We need to understand much more about herbal safety, because herbs generally are much safer than conventional medicines—the evidence is pretty overwhelming around that—and we need to have thoughtful levels of regulation with the MHRA. I share with John that we need a better process within our regulatory and safety processes, to take account of things which are not standard pharmaceutical agents, and a process which allows us to have good, critical and thoughtful scientific review that is relevant to the disciplines, so that these new and old medications may be reviewed properly and scientifically.

John Hardcastle

Our dealings with the MHRA have been pretty good, but, as far as I am aware, we are the only company on the planet that has regulatory approval in the way we make our product, and that is where most of our money has gone to date. It is not that the MHRA are difficult, or the FDA or any of the rest of them for that matter, but the mentality makes it very difficult to bring new antimicrobials through quickly.

David Tredinnick

The UK Five Year Antimicrobial Resistance Strategy 2013 to 2018 states that the development of novel therapies is an important element of the multifaceted approach to tackling ARM. Do you then feel that more resources should be dedicated to your work, and that this falls into the category so described here?

John Hardcastle

It certainly falls into that category. I get very nervous about suggesting that more money from Government should be placed behind our company or our initiative, but what you should think about is changing the landscape so that both big pharma and the venture capital community will put private money behind potential new antimicrobials.

Professor Lewith

The answer to that, I would add, is that the MHRA has been really helpful, but they are surrounded by a regulatory system that makes it sometimes difficult for them. The situation with herbals is very difficult because herbals are not easily patentable, and also many nutritionals, which may equally be effective. We have a big trial that is in debate at the moment about using nutritionals in care homes—vitamin D and probiotics—to diminish or cause antibiotic prescribing. You have talked about care homes, and it could have a big impact if we could do that. They are very simple, cheap supplements, but they are not patentable, so it is very difficult for us to combine with industry to do that. We need to do that with Government‑funded research boards, and that is difficult with the present structure.

David Tredinnick

Developing this theme for a second, according to a submission from the Chinese Medical Institute, research in China tells us that the “immunomodulatory actions of traditional Chinese medicine formulations have a stimulatory effect on immune cells, immune organs, cytokine production as well as inhibitory effect on inflammations, allergies and autoimmune diseases. Studies on acupuncture have shown that this treatment can increase the release of endogen opioid peptides—”

Professor Lewith

Endogenous opiates.

David Tredinnick

Thank you, Professor. “—that affect the immune system. Indeed, acupuncture can strengthen the immune system. The effect can be further enhanced with acupuncture when combined with Chinese herbal medicine”—and western medicine. Is this not something that we should be looking at more carefully? They have a body of knowledge there that has been developed over thousands of years.

Professor Lewith

We are. First, we are looking at it. Secondly, that is a bit of a claim, and I will just leave it at that. Thirdly, you are unlikely to go to your GP in London and get acupuncture for your chest infection. That is not going to be cost‑effective. That is not a reasonable thing to expect the NHS to pay for. But, for instance, we are currently doing a study in Southampton on recurrent urinary tract infections in older women, which is a big problem for a significant minority of older women, in which we are using Chinese herbal medicines instead of antibiotics. We think that they act in several ways. Interestingly, they act to block the cell membrane pumping the antibiotic out. One of the ways that the body becomes resistant to antibiotics is that it gets rid of them from the bacterial cells very quickly; synergistically, the herbs appear to stop that membrane transport pump, so the antibiotics can stay in the cells for longer. One of the actions of the particular concoction of herbal medicines we are using does that. It also has direct antibacterial effects. The whole point of this process is that we can do this, and we can do it very scientifically and very thoughtfully, but we cannot do it in an easily patentable way, and commercialisation is difficult.

Dr McIntosh

One needs to remember that there is an overwhelming body of scientific evidence in favour of immunisation and vaccination, and that immunisation and vaccination is preventative. To crystallise your point, do you want to go down the path of treatment or do you want to go down the path of prevention? I think prevention is, ultimately, in the short term and the long term, going to be the way to combat antibiotic resistance.

John Hardcastle

I am a big fan of vaccines, but all I would point out again is the time line. Traditionally, vaccines work better against viruses than bacteria, and I am not sure it makes commercial sense to develop vaccines against all bacteria that cause problems, simply because not everyone gets infected.

David Tredinnick

I have just one more question. I think I am right in saying that none of you are qualified as homeopaths, but, Professor Lewith, I think your submission was in conjunction with Dr Peter Fisher, who is the Queen’s physician.

Professor Lewith

He is.

David Tredinnick

He also runs the London hospital for integrated medicine. He draws attention in your submission—I assume it is him—to a health technology assessment commissioned by the Swiss Federal Government which found that “29 clinical trials of homeopathy for upper respiratory tract infection or allergies found 29 clinical studies of which 24 were positive for homeopathy.” He also refers to a study supported by the Indian Ministry of Health, which “involved collaboration between conventional ear, nose and throat specialists and homeopathic doctors in a randomised controlled trial of homeopathy versus conventional treatment in acute otitis media.” It suggests that the numbers of antibiotic prescriptions in the homeopathically treated group were much lower. Although this is not particularly your field, would it not be sensible for us to make further investigations in this field to establish whether its usage is effective?

Professor Lewith

There are two things. First, I agree that vaccinations are very important preventatively, but you are not going to stop every virus or bacteria with vaccinations. We need some interventions. Secondly, as far as homeopathy is concerned, this Committee has been around the corner very publicly with homeopathy previously and I do not want to get involved in that. The biggest impact a general practitioner has in a consultation is the consultation. When you consider that we have an ageing population with multi‑morbidity, pain, arthritis, hypertension, irritable bowel, headaches and all sorts of things, for the vast majority of those chronic illnesses, except perhaps hypertension, the biggest response is to the consultation, not the medicine. If you go to a GP and get a homeopathic medicine, it may well be a placebo, but you may go away without using your antibiotics. That happens quite a lot in France and it seems to be quite an effective way of minimising antibiotic prescribing. If you wanted to know whether homeopathy really worked for these infections, then you would need to do more clinical trials, because the trials are promising but small. There are about 80,000 medically qualified homeopaths, mainly in France and Germany, who use homeopathy in this situation quite regularly, and the evidence is that they use many fewer antibiotics. Whether that is all placebo or real effect, we do not know yet.

Chair

Before we move on, to help my understanding, could micro‑organisms develop resistance to either the bacteriophage approach or indeed the herbal approach?

Professor Lewith

Resistance in micro‑organisms is very interesting. If you go back to the genome of the micro‑organism, you note that they evolved with fungi. Most of our antibiotics are fungi. There is an interesting theory that quite a lot of the current antimicrobial resistance is the reawakening of old evolutionary genes. If you remember Fleming’s experiment in St Mary’s, the fungi flew in from the window, sat on his plate and the penicillin fungus killed the bacteria. Our antibiotics largely come from fungi that have co‑evolved with bacteria.

Chair

So the answer to my question is yes.

Professor Lewith

Yes. The argument here around vaccination and stimulating the immune system becomes very powerfully preventative if you look at the evolutionary context of antimicrobial resistance.

John Hardcastle

Just for a bit of background, phages have been around for about 3 billion years and bacteria just afterwards. There has been, for want of a better expression, an arms race going on between the pair of them for a long time. Every day about a quarter of all bacteria are killed by phages worldwide. To be clear, the way they apply them is as a cocktail, so that you do not get that concern practically.

Stephen Metcalfe

Further research seems to be key to finding future developments. Who should be the main funders, or who are the main funders of the various types of research that are going on?

Dr McIntosh

This is obviously relevant to a big question for vaccination, because vaccine‑developing companies invest hundreds of millions of dollars and pounds in developing new vaccines. Universities and biotechs are often involved at very early stages, but then you get to the very expensive part of doing the big clinical trials, which we have all referred to. To get these products approved one has to do clinical trials. The question then comes on to the value that the particular product—the phage, the homeopathic, the vaccine, obviously, or the antibiotic for that matter—will have to the NHS in reducing cost. The balance is the amount of investment being put in and the cost-benefit to the national health service that will come out—the reduction in antibiotic prescriptions, the reduction in antibiotic resistance. My quick answer really is that in appraising vaccines—I am not going to comment on the phages or homeopathy—we now need new ways of appraising using health technology assessment to assess the cost‑effectiveness of vaccines, not only in the community but also within the hospital setting.

John Hardcastle

Stephen, did you mean as in who should be picking up the tab for the development of new antimicrobials?

Stephen Metcalfe

No, non‑chemical antibiotics. Who is funding the research that is going on at the moment?

John Hardcastle

I would say that any antimicrobial—it does not really matter whether it is a vaccine, a phage or a new drug—for the most part should be funded by the private sector. The reason I say that is that you need to ensure that everyone is appropriately incentivised. The reason there are few new antibiotics coming along is that it is not worth big pharma’s while to put their effort there. That is why, if you look at the top selling drugs, they are antidepressants, cholesterol reducers and the like. What you need to do is change the landscape to encourage those with very deep pockets to take advantage of the good work that is done in academic centres already. It is not an issue about a lack of good ideas. The real issue is when it gets expensive and you have to make it worth while for those with deep pockets to make a turn.

Professor Lewith

I agree with that completely.

Stephen Metcalfe

I was just going to use you as an example of why you may not agree with that.

Professor Lewith

Thank you. We can always turn the arguments round the other way. I think what John is saying is that we need different kinds of processes to incentivise companies. There are lots of big herbal companies in Europe—unfortunately not in this country because we seem to be in the process of destroying that industry at the moment—that produce very good quality products and want to work with us, and we need to make that easier and more feasible. We need to understand that if they are going to invest £1 million in a clinical trial they need to have something out of that. That then comes back to the process of patenting and how we manage that institutionally. People are willing; we just need to create the right environment for that to happen.

Stephen Metcalfe

That was my point. You were saying how difficult it was to patent herbs. Can you give us some direction that we should go in, to try and resolve this, rather than saying “This is the problem”? We can all see that. What is the resolution to that problem?

Professor Lewith

The resolution is to have commitment from both public and private joint ventures that work well, because if you incentivise people they work harder and they do not sit on their bums and expect the Government to pay. I think that is really important. The other thing is that we can create patented remedies around two or three herbals that might do this, and they might be very effective mechanisms of symptom control; some of the big Chinese companies are really interested in this. We need to reach out to them and get our MHRA inspectors going into China to make sure that these products are produced to good manufacturing practice. We need to be more open in our universities and incentivise them to set up joint ventures, and we need to have facilities within the MHRA so that they can understand and facilitate—not drop standards—and bring in the skilled people who understand these processes and can let us work. I think if we can do that, it is not expensive: it needs legislation and a few people.

Dr McIntosh

Could I give you a concrete example of why big pharma might not want to invest in antibiotics or vaccines? The concrete example is the vaccine I referred to before, Bexsero, the meningococcal B vaccine, which has had a huge amount of investment and approval in Europe but recently got knocked back by the JCBI. Now of course the JCBI is reviewing that decision and putting some new inputs into their model, but for big pharma, let us say, the investment that one has to make in a vaccine such as Bexsero, or a vaccine for Staphylococcus aureus, E.coli or Acinetobacter, is huge, and the tools we have for measuring the potential benefit for the NHS and the health system in general are not the best tools. That is a concrete example where I think a big pharma company may think twice about investing huge amounts of money in any intervention if there is not more of an assurance of it being recommended—whether it be a phage, homeopathy or a vaccine such as Bexsero, which is now available to prevent the most common cause of childhood infectious death in the UK. One thinks, “This is a huge investment, but is this product or vaccine going to be recommended?”

Stephen Metcalfe

It strikes me that barriers to the research are the regulatory framework and the tools that are used to work out that cost‑benefit analysis. Funding is an issue because of some of that. Are there any other barriers to people investing? The will? Is there a will to research?

Professor Lewith

There may not be a will to research certain things like phages or herbal medicines; there may not be enough investment academically to do that. Setting up one or two centres of excellence would be really helpful and can be done relatively cheaply in joint ventures with specific universities that express interest. Small amounts of money can be used to seed things. If you get the academic interest and get people on side, in the clinical professions, you can begin to make things change.

John Hardcastle

My experience on this has been that we have had to go outside the UK to tie up with centres of excellence in our business, but really there are three things you need to think about. First, you need to think about changing when the patent time starts ticking. Rather than it being when you apply for a patent, you need to tie it to when you can sell the medicine. Secondly, you need to think about why it is that those folk who set the drug tariffs believe it is worse to die of cancer than it is to die of pneumonia, because right now you can get a heck of a lot more money for a new drug against, let’s say, bowel cancer than you can against a new antibiotic or antimicrobial. Thirdly, you might think about supercharging EIS relief, which should be relatively straightforward. You are not going to be able to pick winners, so what you should be thinking about is saying that those folk who are prepared to back companies in our situation need to be encouraged to divert more of their spare cash away from, let’s say, a bricks and mortar deal or a software development company into antimicrobials.

Stephen Metcalfe

Thank you. There is a proposal for a Diagnostics and Stratified Medicine Catapult Centre. Do you think that is the right approach, or do you think we should have one that specialises in antibiotics research and things associated with that—diagnostics?

Doris-Ann Williams

We were delighted in the diagnostics industry that the TSB recognised the importance of having a Catapult to get diagnostics used, and that stratified medicine is across the whole health care continuum, diagnosing, ruling out, monitoring and managing disease as well. I would be highly in favour of that continuing along the plans that they have got going at the moment.

Stephen Metcalfe

Does anyone else have a comment on that?

John Hardcastle

It would probably be no bad thing to align those kinds of initiatives with the import that Dame Sally gives, but I would say that the diagnostic aspect is absolutely critical.

Pamela Nash

You have covered quite extensively the barriers to research in the UK. Could you tell us a bit more about barriers to introducing new techniques to the market, apart from research?

Dr McIntosh

First, I will make a broad comment, not necessarily about vaccines. We do value more, I think, interventions for the elderly end‑of‑life type of approaches which may extend life perhaps by a few months or improve quality of life in older people and the elderly, and there is nothing wrong with that at all.

Pamela Nash

I am sorry, Dr McIntosh, when you say “we”, who are you referring to?

Dr McIntosh

I am saying “broadly speaking”.

Professor Lewith

Are you making a comment about the age of politicians now?

Dr McIntosh

I am speaking as a paediatrician; we could spend more investment and resources at the beginning, in childhood, in paediatrics. I am speaking, I guess, as a paediatrician more than anything, again not devaluing what is done for elderly people and older people, but I think we could perhaps start to transfer the focus to earlier times in life, childhood, paediatrics and even neonatology, with vaccines coming in for that area as well, where we can really improve not only the quality of life but the length of life by preventing childhood infections. Secondly, preventing childhood infections with vaccines has been shown to have a benefit for adult and elderly populations as well; the pneumococcal and influenza vaccination programmes are cases in point where an intervention in childhood has an extreme benefit in the adult and elderly population. I think we can start to link up a little bit the beginning of life and the end of life.

Pamela Nash

I would be quite interested to hear, Ms Williams, about the barriers that BIVDA feel are prevalent in the UK, particularly within the NHS.

Doris-Ann Williams

One of the barriers is the financial flows around the NHS systems in both England and the developed nations. Pathology generally has a budget to provide the testing for all of the hospital care and local community care as well, and that means that there is a restriction on the amount of testing that can be done. One of the things we would like to see, wherever tests are specific to a patient pathway, is that the relevant department actually picks up the costs of that, because, as we have said, the cost of a diagnostic test is relatively cheap on the whole and the value it provides is much higher. But if you have a restricted silo budget for numerous tests on respiratory infections—respiratory infections are the second of the main causes of admission to hospital—and if you have an old‑fashioned microbiology lab, which will very effectively pick up the cause of the infection but will take time to culture those plates up, it is very difficult to introduce a new technology that will be slightly more expensive but means that the patient could get the right antibiotic therapy within five hours of being admitted.

Pamela Nash

I know we are running short of time, but I am interested in everyone’s view on this, particularly yours: do you think that the new structures within NHS England are going to be a help or a hindrance to getting new techniques through?

Doris-Ann Williams

At the moment, it does not look like the situation for us has changed significantly. Maybe it will and commissioning may help in that, but one of our problems is the lack of awareness as well; we need to make physicians aware of the tests that are available. We have talked about CRP, but there are simple swab tests that could be used in primary care that are routinely used elsewhere, which just give a colour-change reaction in the same way as a pregnancy kit. They take seconds to do and cost maybe £1 or £2. We have to find a way of financing that, but it is about educating GPs. I even thought that having a biomedical scientist working in the community would be a way to support GPs’ workload for that sort of point‑of‑care testing.

Professor Lewith

We have a uniquely refined primary care research structure in the UK which is probably the best in the world, and it is really well funded. It has not been dramatically affected by the NHS changes, because it is mainly an academic and NIHR‑funded structure. There is a huge amount that we could do if we took co‑ordinated and thoughtful action on this. It is very attractive to large pharma to do that kind of work in the UK, because they know it will be high quality. We could do a lot of these things here, within the community, very effectively and earn money from them.

John Hardcastle

You asked about the barriers, as I understood it, in relation to the NHS. The issue for us is cultural. There is a real familiarity with using antibiotics to sort out infectious disease, and it is not necessarily easy for clinicians to have to deal with a number of different approaches to killing a troublesome bug, so there is going to be a cultural issue.

Pamela Nash

When you say a “cultural issue”, who is this affecting? It is the same with what you were saying about BIVDA; there is a high recognition within this place, for instance, about what BIVDA does.

John Hardcastle

Say, for example, that someone comes in and they have an infection, the typical response would be a broad spectrum antibiotic, initially. If you have rapid diagnostics and you know exactly which version of a bug is causing you difficulty, you could apply a narrow spectrum treatment, which would give you a better outcome, but it would require a different approach by the clinicians treating the patient.

Professor Lewith

The medical culture, not the culture in the House of Commons.

Chair

Can we pin this down a bit more? There is a UK antimicrobial resistance strategy 2013‑18. Does that strategy encompass fully the approaches that each of you is adopting? If not, what amendments would you recommend? I will just go down the table and ask that.

John Hardcastle

I know phages are mentioned on page 18, so yes is the short answer. The key issue is the funding.

Chair

Dr McIntosh?

Dr McIntosh

The strategy is a good document but it does not explicitly or implicitly state that vaccination has had a role in reducing antibiotic consumption or antibiotic resistance, and does not implicitly or explicitly state that in the future vaccination has a role in reducing antibiotic resistance.

Chair

Can we leave Professor Lewith till last?

Doris-Ann Williams

I think the strategy is excellent. It does mention diagnostics. I was quite surprised in the earlier session to hear that GPs are not considering prescription of antibiotics. When you think that must be the most common prescription they write, you would think they would look for a tool and that that would still be at the forefront of their mind.

Chair

The reason I left you till last, Professor Lewith, is that I want to split the answer in two from you, one in respect of what you said about herbal and the other in response to David Tredinnick’s question, your response on homeopathy, because I guess there must be two separate answers.

Professor Lewith

Yes, there are.

Chair

Professor Davies is on record to this Committee and talking to the Lords as saying that “outwith the placebo effect, homeopathy has no impact. I am very concerned when homeopathic practitioners try and peddle this way of life to prevent malaria or other infectious diseases. I am quite clear about where I believe the evidence is.” I am presuming you might have two separate answers.

Professor Lewith

Let’s answer the difficult one first. I do not think you should be using homeopathy with malaria; I think that is outrageous. In dealing with acute infections, the actual evidence, if you look at it, is unclear as to whether it is a placebo or not. With the greatest respect, I do not think Dame Sally Davies has perhaps studied that evidence in any detail, but I think the jury is very much out on that. I do not think it is conclusive. I would support that by saying that you can look at the same data in two separate Lancet systematic reviews about homeopathy and come to entirely opposing conclusions, which, to me, means there is not enough data. As to the second, in terms of herbal medicine, I agree that the policy is a great policy. I have read it and I think it covers most of the issues. I think that the issues around herbal medicine are around regulatory issues and facilitating expertise in the UK, and within that context, with very small changes, we could do some quite interesting things in the same way as they are doing in continental Europe.

Chair

I thank the panel for their presentations this morning. It has been a very interesting morning all round. If you have any additional information you would like to submit, please feel free.

Jim Dowd

I have one brief question, if I may, Chair. If phages are killing a quarter of all the bacteria in the world every day, how come there is still so much of it about?

John Hardcastle

It is those pesky bacteria that go and breed the next day.

Chair

On that point, thank you very much for your attendance. Oral evidence: Antimicrobial resistance, HC 848 37