The All-Party Parliamentary Group on Lyme Disease
Minutes from First Evidence Session of Enquiry 8th May 2018
Prof Saul Faust (SF), Chair of the NICE Lyme Disease Guidelines Committee
Dr Norma O’Flynn (NF), Chief Operating Officer of the National Guidelines Centre
Michelle Donelan MP, Co-Chair (MD)
Simon Hoare MP, Co-Chair (SH)
Countess of Mar (CM)
Teresa Pearce MP (TP)
Lord King (LK)
Baroness Masham of Ilton (BM)
Hannah Bardell MP (HB)
Alex Chalk MP
Adam Wintour, Secretariat (AW)
MD : Thank you very much for coming this is the second session of the APPG and first evidence seesion of our enquiry. There are a number of charity members and stakeholders who are in the audience who will be observing today so we will go round the room to ask guests to identify themselves.
MD : I would like to ask about how the committee was formed. I believe there was a few calls for committee members, was it difficult to get people to join the committee?
SF: Not particularly, I have sat on a number of committees and this one was no different or more challenging than any of the others. The scope of and Committee is pre-set and NICE has guidelines to follow for appointing committee members and the specialties needed which were followed in the selection. Prior to selection of members interviews were conducted and appointees made on the back of these.
MD: Are there any follow-up questions about the committee?
Lord Trees: Was there a specialist microbiologist?
NF: Yes there was, Tim Brooks.
LK: Going back to the application process was there any conflict-of-interest identified in the physicians and microbiologists on the committee?
SF: The NICE process is very strict and set parameters for what is a conflict of interest.
LK: Welcome to the first meeting of the All-Party Parliamentary Group, this really formed because people thought nobody is paying sufficient interest with the concerns about and the impacts it’s having is much wider than has been appreciated. The opening meeting when we formed its group was an amazingly big turn out of MPs from all over the country who’d had cases of Lyme disease. I think that impressed us all. But the impression of the NICE committee is that it doesn’t go much beyond deciding whether the NHS can afford it. Is that an unfair?
SF: Maybe you’re asking the wrong people for that . I’m a pediatric infection… with clinical academic because I work and live on the South coast of England and the New Forest is said to be one of the areas where Lyme disease is. And in my NHS clinical practice, because I don’t do private work, there are a steady stream of children with genuine Lyme and some children who didn’t have Lyme. I was an interested specialist and I took the opportunity to apply having chaired the Sepsis guidelines. I took the opportunity, as that was finishing, to take on a second guideline because I was interested in coming up with a pragmatic guideline for the NHS that would also perhaps set some boundaries for where research is needed for the NHS in the future.
And Norma (O’Flynn) is the director of the guideline centre.
So we are interested parties. We have taken on the remit to come up with the guideline. So I’m not quite sure what you’re asking?
LK: I’m trying to understand what a NICE guideline committee actually is expected to do? It reports to the Department of Health?
SF: The Department of Health commission NICE to produce a guideline on topic X or Y. NICE then commission one of their six groups, or six parts of their organisation, to produce a clinical guideline. Then a public scope consultation takes place to develop the scope.
LK: Are the clinical guidelines how to treat it or what can be afforded?
SF: We were asked to produce a guideline for the diagnosis, investigation and management and treatments. How to diagnose Lyme disease and how to treat it. That was the remit and there were a series of the questions which we had to answer by looking at the evidence which is currently available. And there is a very, very strict way that NICE sets out as to, which is globally leading, as to how we look at clinical evidence? Health economics is important but secondary to the evidence review.
LK: And so if you produce a guideline, the understanding of how to treat it, the understanding is that the treatment that you advise as affordable in the NHS?
NF: A guideline doesn’t actually do an affordability test. A guideline does a cost effectiveness test, if that’s relevant. So it’s about whether it is cost-effective. Whether it’s affordable by the NHS is a separate issue from what the guidelines are asked to do. So we actually don’t look at that affordability, per se, in the actual guideline.
LK: So if they pass your tests, their costs will be met?
NF: I suppose that is a separate discussion then between NICE and NHS England if it looks as if it’s something that’s above what the NHS can afford. But that’s not something the guideline deals with. We don’t deal with affordability.
HB: Sorry for my late arrival I’ve travelled down from Scotland I’m Hannah Bardell… somebody who has a double interest. I was been by a tick in Scotland years ago. Very luckily diagnosed as soon as I went to my doctor, touch wood I’ve not had resulting symptoms.
I do have a constituent, who has contacted me, she has what she believes to be chronic Lyme disease. She has had an horrendous experience by all accounts. One of the things she wanted me to raise was just whether, her personal view is that the NICE guidelines developed, she understood that the guidelines were not sufficient. They think they do not take into consideration international expertise. I’m not sure whether that is the case. One thing I wanted to ask, she has done a lot of research into this and has been treated internationally as well. She says there are international protocols for diagnosis and care and will this be something that the panel will look at? What is being developed in other countries? I’m no expert.
SF: There are two parts to that question. One is how the NICE process works, which I’m sure Norma can answer. Very, very briefly, just to answer the previous question, we didn’t have any issue with health economics with this guideline because none of the treatments for Lyme disease come up with any thresholds. So money wasn’t an issue for this guideline. At no stage did anybody say to us what you might be looking at, might cost the NHS more money. It was straight clinical decisions based on evidence for this guideline. It’s different if you’ve got expensive cancer treatment.
LK: It didn’t involve expensive drugs?
SF: Correct. To come to the problem of what is termed by some people as chronic Lyme disease, I think one of the very early decisions that we took as a group as a consultation, in a stakeholder meeting, was that it is very obvious that nobody was ever going to come to a consensus about definitions if we were going to try to start defining what was or was not chronic or long-term Lyme disease but there was an acknowledgement by everybody that we have people with symptoms and people without symptoms. Some people with symptoms who’ve had treatment, some who haven’t yet had treatment and so we were quite deliberate in avoiding terms that might lead to noise and avoid us getting to what we can actually do for patients and people who have got symptoms.
In terms of the NICE process, Norma will come back to that but when you look, as a clinician, in a teaching hospital, secondary referral centre for children who may or may not have Lyme, what is absolutely clear is that many of the people, who have felt the need to go privately or it to go internationally, have on many occasions been advised by people who don’t have an NHS practice and/or have had diagnosis made on tests that are known to be even less robust than the bad tests, if you like, or the test we use in the NHS.
I’ll give you an example of another patient who came to my clinic with something called an Elispot test, positive. And Elispots are notorious, they are used for TB diagnosis, especially in children but also in adults. They are known to have a vast number of different conditions that make the test light up because what the test does, it takes immune cells and puts the proteins from the blood on them and it sees whether they light up. It says you’ve made that before But there are an awful lot of things that make Elispots light up and you can’t just diagnose Lyme disease on that Elispot. Yet this German laboratory had diagnosed it on that single test without any secondary evidence. I think it is really difficult in committee, to talk about individual cases and I wouldn’t want to. I’ve no idea which service your constituent had been with.
But I think what we had to come up, for the guideline, was symptoms or no symptoms, diagnosis or not, to come up with the best possible diagnosis and treatment based on the evidence that we have. Knowing that we could also set the boundaries for future research as to what is known and what is not known. I’ll hand over to Norma because the NICE process is internationally known for being one of the best at coming up with clinical guidelines based on proper evidence.
NF: So, in this guideline there is almost no research from the UK. So almost all the research is actually International research and the usual process would be to specify if you were excluding some country because you thought the disease was different there, or something like that. But there was no limitations on countries in terms of any of the evidence we looked at.
MD: So does that signify a lack of evidence and research in the UK then?
NF: We found almost none.
MD: But that signifies something we should be doing as a country if we want to gain a greater understanding and progress in the end.
NF: So we’ve made several research recommendations in terms of the areas where we think it would be beneficial to be able to inform…
MD: And that was your key takeaway, would you say?
SF: I think the key takeaways for the guidelines were to actually establish which tests should be done according to what we know now. Internationally, so these are European standardised tests. Public Health England Laboratory and the National Reference laboratory in Scotland, both act within a network of the European laboratories that offer the standard of care tests and cross reference / standardise the test by quality assurance process between themselves. So we can be absolutely sure that the PHE (Public Health England Laboratory), in Salisbury/ Porton Down, is doing the best test they can possibly do, to make a diagnosis. There is a debate about whether they should do other tests as well, that’s separate. Should we be doing the test they are doing, yes, because it is the best test we have at the moment both on the screening and the definition.
What should we treat? The guideline, that we came up with, we appreciated that many people say they haven’t received enough treatment and many say they haven’t received any treatment; and that’s a problem because the awareness of Lyme disease needs to be raised, which is what the guidelines try to do. If you raise awareness, get people to make a diagnosis and the guidelines allows to make a clinical diagnosis without a positive test.
So it says to clinicians, if you suspect Lyme disease, even if your tests are all negative, you can still offer three weeks of antibiotic and in the treatment section, we made sure that the doses are at the highest doses that can be prescribed, not half doses that may not lead to doubt.
MD: You wanted to come in on testing?
CM: On the testing, the committee recommends the use of C6 ELISA serology test, however in the appendix on research recommendations, you state “Current literature suggests a combined IgG and IgM ELISA based on the IR6 peptide and immunoblot are useful; however published evidence is that they are of very low quality and it is not UK based. There is evidence of variation in the IR6 peptide between the principal Borrelia genospecies…”
Based on these statements what justification does the committee have to recommend the C6 test for use in the UK, for UK species of borrelia?
NF: I think it’s the best test and the best evidence we have. To go back to Saul’s point, even if it is negative, you can still diagnose and treat.
SF: And I believe you are inviting Tim Brooks to come to this committee. He is one of the European experts on these tests and other tests for other infectious diseases, he would be the right person to go into the detail of those.
CM : You will be aware that there has been a lot of criticisms about your denigration of tests from abroad for various reasons. You say that all laboratories must be accredited by UK accreditation service UKAS. This organisation accredits two standards: CPA and ISO. ISO is a worldwide quality management standard, with only one authority in each country, allowed to carry out accreditation. For example UKAS in the UK and DAkkS in Germany. It is not possible for a German authority to be ISO accredited by the UKAS. They must be done by DAkkS. However the quality standard for microbiology laboratories which is ISO 15189 is identical. Does for the committee recognise that it infringes the European trade laws?
NF: So the guidelines is for the NHS, so the recommendation which is that it should be UKAS, is because it is an NHS guidelines. It is not in any way saying that whatever is done elsewhere is incorrect. But it is for people in the NHS. The other question is about what people do with tests from elsewhere. If those tests are accredited elsewhere and validated elsewhere. The guideline isn’t saying that they cannot be used, but the guideline is for the NHS.
CM: In response to my previous question, it would appear that you won’t accept tests from Germany, for example ?
SF: So, where the laboratory is considered accredited, within their own country, then the guidelines are clear that those tests can be used. The problem is that many of the people who run Lyme clinics internationally, do so in isolation. They haven’t published their work and on many occasions they are often there to make money from their clients and not necessarily to do the best evidence-based approach, according to what many people globally might consider, the best data available at the moment. What I mean by that is if I decide to set up a private Lyme clinic in Southampton, I could charge people a private amount and send my tests results wherever I like and I wouldn’t have to use PHE, I might find a lab that makes a lot of Lyme diagnosis and I might find I’m using a lot of of doxycycline. But that’s not necessarily the right thing to do, even if people are happy with the antibiotics I give them.
CM: I happen to know of one hospital where they do Lyme tests both in the states and in Germany… and that they are criticised for it.
NF: I think the other recommendations in the guidelines will say if there is any doubt about what the tests that have been done, then people need to think about it, you shouldn’t base it on a test you don’t know about and it doesn’t fit the clinical picture, I’m sure that’s what the later recommendation says.
SF: And just to go back, we had to come up with something that was pragmatic for NHS patients. Even if the tests are negative and the clinician or the GP or the hospital specialist thinks Lyme is a possibility, there is still the empowerment to use up to two courses of antibiotics to treat that person. The committee totally agree that there is doubt, and quite often it’s the right thing to do with such a cheap and relatively safe intervention, is to use it.
CM: … if in doubt be bold.
SF: But it seems very reasonable and reasonable to the committee that the three weeks, or two times three weeks, of antibiotics for the sake of making absolutely certain to that patient that the disease has been treated, if they had it, is a reasonable thing to do.
CM: … and that’s the importance of catching it early.
SF: If you can and of course awareness and raising awareness amongst all clinicians and practitioners is one of the key things of the NICE guidelines.
MD: I think we should move on to Lady Masham and then Simon.
BM: I wanted to ask, where there is insufficient evidence, what changed NICE’s idea, did they realise there is no evidence now. And are you looking at Europe because I employ a lot of European staff, many of them know all about Lyme disease. It’s in the forests and the doctors seem to know straightaway if it is Lyme disease. Do our doctors and GPs know enough? I wonder if your committee is looking at Europe because they do have a lot of evidence.
NF: So, the committee comes together just for the guidelines, that committee has now stood down. The committee did have people from areas of the UK. In Scotland we had a member who’d previously worked in Sweden, so people had a lot of their own clinical experience of treating Lyme disease and I think that ability to recognise a disease, partly depends on how much of it you see. And so we tried within the guideline group to have members who have that experience including people who came from particular areas in the country, where they saw more Lyme disease than other people did.
SF: You’ve hit the nail on the head, if you like. In countries where it is so common that doctors are seeing it the whole time, it’s relatively quick for people to think “this might be Lyme” and to do a test and to treat. It doesn’t stop in those other countries considering a differential diagnosis, it’s just that there, the balance is different. In the UK, even in areas where there is a lot of Lyme, there is still not as much as in those European countries.
One of the purposes of the guidelines is to try and say, actually not many doctors know very much about Lyme in the UK, absolutely, and that’s an opportunity for the NHS to say, look, this is what you should think about, this is what you should do and is why it starts at a very simple level.
BM: So you are sending enough publicity out to GPs?
SF: So, as I experienced with the Sepsis guidelines before, the implementation part of NICE is, perhaps, not as funded, to the extent as the guideline development. Perhaps you might want to ask that of Mark Baker when you see him.
NF: I suppose yes, the British Medical Journal did a summary of this. There is other work going on which we are doing with the committee to try and spread it as much as we can and through spreading gradually through education.
SF: It’s fair to say that NICE committee members, listening to both the committees I’ve done, are often frustrated that there is not some central process to disseminate more widely. It is left to NHS England and journals, as Norma says the BMJ has produced something, one to the GP journals is going to, and a nursing journal contacted us to ask is there anybody who could right piece for them. So the momentum is there, it is a question of not losing it.
BM: You have a website on a computer so they can put in Lyme disease.
SF: If you put into Google “NICE Lyme disease”, the revision of the NICE website is much better than before, you can find things much better htan before, so a GP in a clinic can easily find information.
TP: You just said with Lyme disease, the more you see it the easier it is to recognise, but we know there are a lot of GPs in the country who have seen it and not recognised it, have seen this a lot and still not recognised it, so the NICE guidelines about the diagnosis and treatment the issue is though, how do you get to diagnosis if your GP it’s completely unaware. If you come from an area of the country like you do, you have a certain expertise.
But there are lots of people who go to pop concerts, Glastonbury, then they go back to their own environment and then their GP wouldn’t know. So the first thing in solving a problem is recognise the size of the problem because we don’t know how much is undiagnosed. How do you solve that riddle? If you do you solve it, is there enough expertise in the country to actually deal with it?
SF: One of our key research recommendations is that we don’t know the extent of Lyme disease in the country. We think there would be a really useful study to look at the seroprevalence, the antibodies, how many people appear to have had Lyme disease and responded, and at the same time, be looking at best treatments and or best diagnosis if we can.
In terms of how you then raise awareness, this is a problem for any condition in the NHS where there are hundreds of conditions which clinicians have to know about and in hospitals, things that are important are sometimes added to mandatory training. In primary care, in general practice, it’s much much harder. And how the country manages the continuous professional development of all its different staff groups it’s not the responsibility of the committee but it is a massive problem for the NHS. Are there enough clinicians in the country to deal with genuine infectious diseases if the diagnoses are met? There are the tertiary and secondary infectious diseases services for adults and children are well developed in NHS England. We are not overwhelmed by people thinking they may or may not have Lyme disease, at the moment. I think, just as important, are the open mindedness of neurologists and rheumatologists and other specialists to the possibility of Lyme disease with people presenting with unusual symptoms and putting that potential for Lyme disease and thinking about it to make the potential diagnosis, into their minds. It’s not just about infectious diseases it’s about all the different specialists and primary care raising that awareness so that people think, oh, these are unusual symptoms, that could be part of Lyme disease, let’s do a test and/or proceed to treatment. It’s a very tricky thing to do with such low numbers as a starting point.
TP: Low known numbers?
MD: The guidelines say you can be referred to a specialist if you have the two courses of antibiotics and got no better but there is then the potentially the scenario to be referred to 5 or 10 specialists because there isn’t a Lyme disease specialist. That is a huge strain on the NHS. It’s not really an answer is it? It’s confusing for a GP to know where to then signpost that person to go. It will then be a postcode lottery as to which GP you have won’t it?
SF: My guess as an infectious disease specialist, is that a Lyme disease specialist isn’t the way to go. We had great discussions with this amongst our public reps on our committee and I do in clinic.
The problem is that if you are certain you’ve got Lyme disease, then there are places to go in the UK you can get referrals within the NHS or even privately. The problem is the unknown, is people who aren’t aware that they might have Lyme disease. How would you know with somebody who is tired or has got unusual joint symptoms? How would you know to send them to a Lyme specialist, as opposed to a neurologist or rheumatologist or a psychiatrist? It’s really hard to know. If you set up a series of Lyme clinics, you couldn’t be certain that the right people would go to them.
MD: Maybe that’s why we need more research, if you do send a person that you do know, are you not then treating the symptoms not the cause. Are you not in danger of doing that?
SF: You are in danger of doing that, that’s right. So, do we have a enough infectious disease clinics for people who have got real infections? I think we probably do. Different people in some specialities may argue about that. Do we have enough awareness of the Lyme symptoms amongst all the other people who this could present to? Almost certainly not. That was one of the reasons why many of us took on the guideline because we wanted to help raise that awareness.
NF: I’m a GP. One of the things you spend your time doing as a GP, is ringing up specialists and saying, I have this person who has this set of symptoms, could you see them because I’ve gone as far as I can. That sort of uncertainty is a very regular part and I think you talk to a rheumatologist about a person who has primarily joint symptoms and the neurologist about the person who has, but neither do you want to miss something else. You want attention to the Lyme, if that’s what it is, and that broader view of which is what the rheumatologist on the group felt that they see and they were comfortable with that
MD: Sending someone to five different specialist is very expensive.
SF: It is not suggesting that. It’s suggesting send to a specialist most likely to make the diagnosis and I think clinicians do seem to understand that. We’ve had a very good feedback from GPs, that they understand what to do and where they might send somebody.
And actually the awareness, just having published the guidelines, the awareness from other specialties seems to be better too.
I’ve had three calls from ophthalmologists in the past three weeks where they have thought about the Lyme, because they saw the Lyme guideline published. They were not able to interpret the test that they’ve done. That’s the whole point.
SH: Thank you, my apologies for being late. It strikes me that part of the problem here is with confidence and credibility. If you are trying to create confidence in the robustness of the NHS in understanding this issue, having a handle on this issue and being able to deploy expertise in this issue, it’s something we are running to try to catch up on.
And that lack of confidence in those elements as far as potential or actual sufferers are concerned, seems to drive the perfectly understandable appetite to seek a diagnosis and advice from overseas clinicians, whether they are dispensers of quack medicine and unregulated by their own domestic regulators, or not. So it seems the first challenge, having secured the guidelines, is to give confidence to the general public. Those who have had an interface with Lyme is that we have a handle on it and I can understand Professor why you say let’s not have a specialist for Lyme but that I suggest that compounds the problem of empathy for and understanding of and response to the, and I use the word in inverted commas, the “epidemic”, Lyme disease seems to be creating. And the appetite of the health environment, the health sector, to respond to it. It’s almost as if there had been the breakout of the Black death and someone decided we are not going to have a bubonic plague specialist today but we might send someone to the vet. And that I think is the impression of the confidence.
SF: So, I agree with almost everything you’ve just said, in terms of awareness and confidence. I genuinely don’t think a Lyme specialist would help. I totally agree with all the other points you made about raising confidence and robustness, making people realise they can come to the NHS to get properly diagnosed and treated. I’m not certain the right group of people would be sent to that Lyme specialist and I’m not certain that the lady with a joint problem, that’s been there for two years, would necessarily end up being sent down the right NHS pathway.
I don’t have any miracle ideas about how we might raise awareness and confidence in the absence of that but I couldn’t agree more with almost everything you just said. We’ve got the guideline, we can use the awareness. How do we then actually make people think they are getting the right treatment. I can only say from my own experience that where you have clinic, and I know that Dr Beeching in Liverpool has the same experience, and other colleagues around the country, where I have a clinic where people come, and they are able to tell you what the problem is, they can explain the story of where they are on the pathway and they are listened to. Then you have a really good chance of either explaining you don’t think it’s Lyme and where you are going to send them or treat them because it genuinely is Lyme. I think the NHS already has those clinical spaces to do that if we address the knowledge, because most GPs aren’t going to see very much Lyme but most GPs do need to know where to send in their region.
TP: They might see it but don’t know they’ve seen it?
SF: You need to recognise it and send to the right place in your region.
SH: Can I just come back to the point, I understand what you are saying. Given the low base of confidence which the NHS starts with with regard to Lyme, I would suggest that, and it may just be totemic and it may be a short term appointment but to have a national lead or expert who can drive forward the knowledge agenda who can speak at the GP conferences and the Royal colleges etc. Probably of itself in the clinical output point of view the benefits of which that that person fulfilling that task would be marginal. But I suggest that in dealing with confidence that this is an issue which is being taken seriously and not just the illness of the moment, the 2018 version of ME, something which is fashionable that people see on the internet and think I must have that… and therefore being driven overseas for different tests because of that lack of confidence, I just think it’s may be the most expensive confidence giver imaginable but to have that sort of national expert who will drive the knowledge build up amongst medical practitioners to give confidence that this is being taken seriously. The value of such a position and person, given the baseline from which we are starting, would actually be pretty valuable. Nobody would say we aren’t going to have oncology specialists.
SF: So I suspect we don’t disagree on the outcome but on the journey to get there. If NIHR were to commission the right research using a mixture of the public and charity money, then the people who consider themselves experts in the UK, would apply for that money and would then become those experts more visibly in terms of their leading the research and leading a national network of people.
Children are a much smaller group than adults. It wouldn’t be for us in paediatrics to lead this research but we absolutely would collaborate on the national application. Using the NIHR research network, I also think all 14 areas of the country would take part in those studies and would recruit and that’s achievable, if that research was commissioned that would happen, whoever submitted the best project would be awarded that and it would happen. And the best clinical services in my experience, are often driven by that clinical research thirst for knowledge, whether its Professor [unclear] in Imperial, in sepsis management, discovered that tuberculosis is a genetic disease or whether its cancer, immunology centres being developed by that research expertise. That’s achievable in the next two to 3 years even if NHS in England can’t see a big plonk of money for just an NHS clinic. It’s hard with our need for equity of access to the population. It’s hard to just create one National clinic. It’s hard for patients to travel. It’s hard for NHS pathways to actually make it possible for people to travel to just one centre, the highly specialised commissioning, for very, very rare diseases, is really quite complicated as well as expensive whereas this is achievable.
I suspect there is too many people with Lyme disease to be captured by a highly specialist Commission.
CM: But your Lyme Tsar would do the travelling.
NF: Tsar is a different model, a Tsar rather than a clinic.
MD: They are not mutually exclusive are they, you can have centres of excellence and the research and still have a person who is accountable to make sure that the tracking is being done and there is progress in the area. You could do both?
SF: You could nominally do both.
MD: Because there is that danger at the moment people are sent to see different consultants and then there isn’t any tracking, actually they become a statistic for a different department in the end, don’t they, in the long term?
NF: But they may still need to see different consultants.
SF: There is no tracking without research, that’s our problem at the moment. We’re in a round and round circle. If you set up a system to track, you wouldn’t have our ability to do the right test on enough people to work out who has got it and who hasn’t. If you set up proper research studies prospectively where you are actually testing groups of people who have haven’t had symptoms in endemic and non endemic areas to look at the seroprevalence and you actually set up System where everybody with the right group of symptoms has a sample sent to the same place, tested in the same way so that we can a) workout whether there is genuine Lyme on current tests but actually (b) look at the best new tests in amongst the one that people who have symptoms and do not.
MD: Has that model been done anywhere else in the world today?
SF: Not yet for Lyme.
But NIHR, do give you a very good process for that to happen because the point of setting up the NIHR was to set the NHS up, our population of 60 million, everybody has access to research that’s delivered within the NHS, that’s the whole point that Sally Davies set it up as an national organisation and the networks are really good, so if you set up each region as a recruiting centre for this and each region has somebody taking responsibility for making sure the right samples come in. That is there.
CM: Three, maybe four years ago, Tim Brooks, in his group, working with the Lyme charities, produced a very simple leaflet for GPs which was sent round to every single surgery, about recognition and what to do about it. What role has Dr Dryden to play?
SF: Dr Dryden is one of the clinicians at Porton. He had to step out of being on the guideline.
CM: Yes, he had been the place to go to as far as the National Health Service is concerned.
SF: …and still is and still very much works with Tim Brooks and with me locally in the region.
Once a NICE guidelines is published, our hope is that everybody then works to it and eventually can revise it, when new evidence emerges.
CM: You were talking about a Tsar. Dr Dryden has played that role for a number of years. He has been the one person to go to who gives an infallible (in inverted comas) answer.
SF: Ok, so I don’t think that Dr Dryden’s practice is any different to many of us in the sense that he is open to listening and doing but he had set up, he tried to set up, because he is in an endemic area, a more open centre for wider referrals but for some reason, I don’t understand the local finances, it wasn’t financially sustainable somehow for that to continue. That’s my understanding, you’d need to ask him why it didn’t carry on.
CM: GPs do have the knowledge… and if GPs go walking they will see notices in the popular areas.
SH: If one was starting off in a medical career in Germany, you are sitting in medical school, does some learned professor give a series of lectures on Lyme? What would a newly qualified German GP know about this?
SF: I can’t answer that but I can tell you until four or five years ago antibiotics were treated as a second-rate drug in the UK medical schools. We spent eight weeks learning about different cardiovascular drugs, of which we would never prescribe as a primary carer because you would get told by a cardiologist, what to prescribe. Yet antibiotics, potentially lethal, resistance causing drugs [unclear].That has switched with understanding. Because medicine is so vast, your local regional medical schools do tend to focus on things that are local.
So I know that within my lectures to students, measles gets one slide and it wouldn’t surprise you that Lyme gets one slide, when talking to students. But they get it and they get and awareness of it. I suspect with medical curricula being what they are, not many places in the world have a very large section on Lyme, but I have no detailed knowledge.
SM: But there must be something?
SF: There is experience, if you are a GP training in our region, you will sit in surgeries where people come in with an EM rash or they have been bitten by a tick, they will experience a GP asking the right questions. Then those people will work wherever, and they will know about it because they’ve seen it. If you only ever trained in London or Birmingham or in a city, you might miss that. And one of the benefits the UK system has always been that experiential training, the apprenticeship.
CM: Richmond Park has a lot of Lyme, from the deer …
NF: You hear that anecdotally from GPs, I think in retrospect, I might have seen that rash once.
TP: in the NICE guideline, it says they are evidence based. What we are hearing is there is under diagnosis, there is a lack of awareness. So how robust is the evidence this has been based on? Surely it’s a snapshot, rather than an evidence based?
SF: I think that would be fair, we’ve said all the way through, the evidence was not what NICE would call high quality evidence i.e. Gold standard, randomised control trials or fantastic cohort studies. Tests done in the same way in all aspects of the study. And from a diagnostic point of view, internationally much of the research has not been published properly. Different standards are being used. In much of the treatment trials, people have used different comparative agents at different doses. And so one of the first research recommendations that we set out is to come up with what’s called, the core outcome set and we’ve learned how to do that in the last 10 years in the UK. The MRC and NIHR put a lot of money into trials units, setting up clinical trials, establishing before they start with the public, Core outcomes sets, not a group of doctors deciding what’s important, outcomes in a trial. They are the outcomes every stakeholder, patients and experts, believe are going to be important to agree, that will then rub through. Every single trial in that condition. If you have a core outcome set, you have to decide what you mean by cure, what you mean by side effects. What you mean by all those different things. Then you agree nationally and internationally. That’s the standard you are going to take forward.
It’s much easier to envisage if you have a bone infection. Part of the core outcome set might it be: pain free, no disability. You might set a length of time it takes to get better on your antibiotics. But for Lyme, people have just done different things for every different study.
So you have to set that first, then you can start different treatment trials. You can compare doxycycline with amoxicillin, you can compare other agents, you can compare new antibiotics, you can do different lengths of treatment. Until you have a starting point, which everybody agrees, you’re not going to design good research.
TP: So a Lyme Tsar seems like quite a good idea?
SF: One person cannot do all the studies. The conduit we have in the UK is for NIHR to commission studies that involve developing core outcome sets because that’s their remit, the best diagnosis and the best treatment, you can do epidemiology as well, as a separate one. They commission that core and people apply to do the research in networks.
TP: If you have Lyme, which is undiagnosed, is it a risk to become pregnant and pass it to the child?
SF: This was a very difficult question to answer. This was a very personal topic to one member of our panel. Apart from a very small number of case reports, that were of very low quality because they themselves didn’t come up with any good answers, yes or no. Babies who have being examined who died of unknown reasons, post-mortem type studies or placental studies. There was no evidence either way.
We came up with, we think, what it is a pragmatic solution for patients. Firstly if a person catches Lyme in pregnancy, you have to be treated with a safe antibiotic. Amoxicillin is the standard at the moment. My guess is that as we get more experience with doxycycline going forward in the future there is increasing evidence that doxycycline is safe in pregnancy and safe in babies. But it is contraindicated under 12 at the moment, in the UK. That’s another story for the future.
We have been very careful to say that pregnant women should be treated, should be investigated and treated for Lyme. And that when the baby is born, and this, I know my speciality colleagues are signed up to, if there is any concern that the baby that is born is symptomatic, then one of the 14 centres that specialises in paediatric infectious diseases should see the child and actually, we have said that if the child is symptomatic they should be treated with or without the test being positive.
So pragmatically, and amoxicillin is a safe drug to give to children and to babies for three weeks it is used for other things, we know that. So regardless of whether we have evidence either way, and I think you can only imagine the debate the committee had. We had to come up with a guideline which was pragmatic for people might be concerned that they genuinely had Lyme in pregnancy and I know it, based on the test said, or that they were worried that they might. I haven’t heard people speak badly of that pragmatism so far.
TP: It is still a concern that there is so much that we don’t know.
SF: It would have to be part of the big research study. If you set up a system where everybody who might have Lyme is having a blood test, you’d be specifically capturing that information, that so and so was pregnant, and this is their test result.
MD: Are you are allowed to be a blood donor or not?
SF: For a research study, of course you are.
MD: I mean in general.
NF: If you check the transfusion site, not whilst you are on treatment is what they say.
TP: It’s one of the list of things…
NF: They do have evidence on the website and in Lyme disease if you have been treated you can donate.
MD: Following on from that point that the whole rhetoric is, there is a lack of evidence, then how did you get to that point that you should have two courses of antibiotics and not three or four? The ILADS organisation suggest 6 to 8 weeks and double the dosage? That’s overseas. There’s lots of different theories on how long the antibiotics go on, based on what you said. The honest answer is, we don’t really know how long to give them for that’s effective, because we haven’t got the research there to prove it. How did you get to do two courses?
SF: So there was a certain amount of research, particularly a very recent study published in the New England Journal of Medicine, that looked at longer courses and found no difference between people actually given intravenous ceftriaxone and not. So saying that the evidence is poor quality is based around things I was talking about earlier, lack of similar outcome sets, not comparing like with like, comparing apples and oranges, not that there was nothing there at all. The current view as previous British guidelines, have been very vague, for clinicians, they have said use 14 to 21 days and dose X or dose Y. And the committee took the view that it’s impossible to for clinicians in that respect that GPs are now more concerned about prescribing antibiotics ……
Generally for infectious diseases you want to be taking a decent dose of something that’s going to make you better and then you stop taking medicine as soon as you are better. Rather than use a lower dose of something that might then cause resistance or problems. So we have used the higher dose regimes. And we’ve gone up to the maximum oral doses according to the British National Formulary (BNF), which licences drugs in the UK, for all of the drugs that are recommended. And we went for the longer of the international guidelines from standard practice, up to 3 weeks because studies had picked 21 days or 14 days to measure, so where we are looking at the evidence, the studies were we give X vs Y for 14 or 21 days. You will notice a couple of the conditions in the guidelines take it to 28 days because one study in that area was done to 28 days.
But there was no rationale, you go back to that study, you look at the introduction, you expect them to say why they did 28 rather than 21 days. There was no rationale, which is why we come back to you’ve got to set your core outcome sets, the terms of reference for the studies as part of the beginning of the process, as a community.
SH: …Given the fact that they appear to be more advanced in a understanding diagnosis in Germany, rather than reinvent the wheel so our research has to be in the UK so it has to be …? What are we going to do in terms of what is prescribed at what strength and at what length, from Germany, because if they are doing it well or better, why don’t we just cherry pick.
SF: As Norma said, most of the research we looked at was not from the UK, they were German they were American, they were Holland and for the rare diseases, so for the rarer types of Lyme, you are absolutely right, you need a European-wide or global study that everybody agrees the protocol internationally and does the same thing.
SH: So who drives that forward?
SF: Again collaborative research groups. You can apply under EU 2020 rules for collaborative Studies… it’s much harder, at the moment, for the UK to lead them now, as you know, but were there to be a European call for children or adults to join in collaboration for Lyme disease, I’m absolutely certain a UK specialist would volunteer to join it. There is no hesitancy, amongst the UK community, in joining International research efforts that is commissioned in the EU or the US NIH or even in the UK.
Unknown: You have anticipated my question, I was about to ask how much you have reinvented the wheel. I haven’t heard the US mentioned hardly at all. We are in a situation in the UK, where the US where 20 or 30 years ago, where the public are actually driving awareness and concern about this. And in terms of establishing aguideline, how much are we able to learn from the US experience particularly?
SF: I think we are way ahead of the US, they ended up with a stand-off and demonstrations outside all their infection meetings. And an inability to communicate.
We had collaborative stakeholder meetings where there was no antagonism and no animosity. People were able to express their view, we had 4 public representatives on the committee, who represented very well the views of the patient and the public and unanimously agreed the guideline but also agreed the lack of evidence and what needs to be done in the future.
NF: And so we used American evidence if it was there.
… one of the difficulties is that the NICE process is looking for a particular type of evidence.
So, so it is looking for a standard of evidence because you’re making guidelines for the NHS. So if there was American evidence there in the published literature, we used it, where it was.
MD: The work of ILADS, did you disregard that? I know a number of the private places in the UK use their guidelines and evidence as a sort of benchmark.
SF: So we tried to go back and find every item of published evidence. You will find groups, I’m not going to name any names, because there are many of them, who say they are using evidence when they are a not. They are using single Laboratory experience. They may or may not be out with what everybody else is doing.
There are all sorts of people who can say they can make a diagnosis of X or Y but unless you publish and people can replicate it, it’s really hard to know what to do with that.
NF: So the NICE process, you start with evidence, you are clearly cognisant of what other people are saying and if you are coming up with something different then why are you sure you are saying that. But the process is to go back to the actual source evidence and look at it rather than how someone might have interpreted it.
SF: As a committee member, the questions we advance in the scope and the NICE researchers go away and see what they can find and come back, they always ask the committee if they know of any paper we’ve missed, is there anything in the published domain, whether public reps or clinicians are able to say, what about this paper, what about this paper. Those are pulled out and the detail is looked at, if they meet the required standard and format they are included.
MD: Are you concerned as clinicians yourself, about exploitation of people who go to private places in the UK and overseas, can cost 1000’s. It’s not just the illness that’s an issue, it’s the fact that is becoming a fast growing market, that exploits people and sometimes doesn’t even get them any better.
SF: I applied for the role of chair because of my experience in my clinic where families who spent tens of thousands pounds going to the foreign clinics when they could have just come down the road. This is about confidence. Unless you have a system where the NHS can confidently say this is where you come, this is what we’re going to do, then people will feel they have no choice. That’s something we have to break, I couldn’t agree more with you.
CM: This is where… problem with my GP saying it’s the latest fashionable thing come.
SF: I wish they wouldn’t use language like that.
SF: This is about medical communication, ultimately. There is no excuse for telling people they are wrong and not listening at the start of a consultation.
CM: Can I ask a very quick question about the EM rash. You say that the EM rash has got to grow. But the GP sees the patient once so the GP doesn’t know whether the rash is growing or not. The guideline says the rash increases in size. It is not possible for the clinician to determine whether the rash is expanding on initial presentation, you recognise this and if the rash does not continuously expand?
Also is the committee aware that this could delay or discount a diagnosis of Lyme disease?
NF: My response would be that it is a fairly core element of the clinical history, asking somebody about the rash that they have when they see you so how long it’s been there, what it’s done. Lots of people now use photos so it’s not at all unusual for somebody to come in with something on their phone, say this is what it looked like last week. Or for me to be able to say, let’s photograph is now and let’s see it again in two or three days time, or call me or whatever. It’s a fairly core part of the medical history to ask about, what happened to, what somebody has, its a very important part of making that distinction.
CM: If you’ve got a GP who understands.
NF: I saw someone yesterday who’d been in their garden that was the discussion. How soon do this come up after you were in your garden. You would really expect most clinicians to be able to do that. You would worry if they couldn’t.
SH: The process that you’ve gone through, it strikes back to my confidence point, what organisation, World Health Organisation, whoever, who would effectively peer review what the NHS, PHE, NICE are doing? From a dispassionate point of view, what you as UK citizen can or will experience in your Health service provider, you should have that confidence in, i.e. They understand it, they got to grips with it their diagnosis and robust scrutiny. You don’t have to default to Germany or the US, the great friend of the world but the great enemy to the medic is the Internet. People go onto the Internet, they type in their symptoms and some people will convince themselves that’s what they have and will not to be satisfied until they find somebody irrespective of the cost, who confirms what they think they have got. That’s the case with every medical condition known to man and to woman.
Given we are starting from, on that confidence ratio, a very low base. What can be done to give that confidence to people?
SF: It’s about perception, you are absolutely right, the Internet is a very powerful thing. We have to remind ourselves, firstly, probably, and this is one of the things that needs testing, most people who get Lyme disease handle the infection without treatment and find themselves to be positive on antibody testing without ever knowing they had it and they have no long term consequences.
Some people get symptoms and get treated very rapidly, some people get symptoms, they take longer, a Rugby player in the public domain, realises something, then has a diagnosis made, then he’s better.
Some people just have a delayed diagnosis. …And then you have your group that won’t try to replicate, you can’t convince.
The numbers of those last two groups are actually very, very small in relation to the numbers of people who confidently have symptoms, get a rash, go to their doctors and get treated.
We do need to know those numbers, they could be anything from… we know PHE have 1100 positive tests last year, even if it were 10 times that number, that is still quite a small number of positive tests given that most people will be better compared to other conditions.
So you’ve got a very small number of people, a relatively small number of people who do have a problem, some of whom will have Lyme disease, and as you said a minute ago, some won’t. I’m not sure of the answer for any group of people who are convinced of a diagnosis that no tests says they have got.
CM: One thing worrying…. IAPT (Improving Access to Psychological Therapies) program thats been rolled out. If a patient goes to their GP and says I’m tired, I have cognitive problems and I ache. Almost immediately they’ll put it in as Medically Unexplained Symptom, and sent off on the IAPT.
How do we make such a patient with Lyme, or any other thing that has these symptoms is not sent off on that route ?
It is such a temptation for a doctor isn’t it?
NF: I don’t recognise that. You can never say those things don’t happen. Most people going to the doctor, its quite difficult to convince people that the cause of their illness may be psychological and go down an IAPT route, in my experience, so you would do that much later in the course of treatment.
CM: It seems, reading the literature, this is going to be the only route for someone turning up with those symptoms.
SF: We hope that if there is any concern that somebody might have Lyme, we’re back to who has Lyme and who doesn’t, then the default position is to be able to give three weeks of antibiotic because you then have had a treatment and you can assess as a clinician whether it has had a beneficial or no effect, or a harmful effect.
AW: Carrying on the point about assessing the scale of the problem, right at the start you conceded that the testing was not perfect and there are varying views on how good it is, but it seems that it is almost impossible to assess the true scale of the problem whilst you still have tests that don’t accurately to say whether somebody has got it and whether they have recovered or not.
SF: So no infectious disease has a test for a cure because you have an antibody response and it’s there and it stays there. All infections are the same.
If you have a positive Lyme test then you have Lyme disease. The problem isn’t when the test is positive.
The problem is with people with symptoms who don’t have positive tests and sometimes people won’t have Lyme disease and sometimes they will, and that’s why research, proper research, where there is a proper capture of the clinical information and epidemiology, where people have been and the outcomes, is conducted so that you can work out of the negative tests, of the tests we have got the moment, how many of those people have Lyme disease and which tests might actually be better used in the future.
CM: Is it a blood test?
SF: We’re talking blood tests for most people, yes, because people with joint problems where you might take some tissue from the joint or some fluid from the brain much smaller problem. So I think for most people, I think we are talking about a blood test.
NF: Can I just add to that the guideline has quite details research recommendations which means that all those people would also be included so the research recommendation is you also follow up people who are clinically unwell and may have Lyme even though the tests are negative.
AW: Do you think that should be separate, an isolated body of research around these group of patients who may or may not have Lyme disease but are nonetheless ill.
SF: They need to be part of the testing because it’s so expensive, it’s so difficult to set up. If you are to set up a process to test and identify patients and then following them up, it all needs to be done as one, with different parts.
As my final comment, if you skip forward 20 years I think that technology for making diagnosis Will be very different. In a research environment, you can already take a blood test on the first day of an infection and based on gene response if you look at 30 or 40,000 genes, you can tell which bug has infected that human being but it takes weeks, tons of statistics to generate that. If you are asking what testing for Lyme is going to look like in 20 years time if you got what you think is an infection, you will give blood spot in an emergency room or the GPs door, and it will come back the following day or even a couple of hours later, have you got a virus or a bacteria, what bug it is, based on the genes, your immune genes that are being produced, that’s in reality, not space age you probably have 20 year engineering gap, to be able to work out exactly how to do it.
AW: There’s a leap from having a certain infection and the symptoms that you have, being associated with the infection. How do you address that issue?
SF: They wouldn’t test positive on that because we would be absolutely clear from where we know people have got the Lyme. What your gene expression looks like if you meet Lyme disease compared to a different spirochete.
MD: People have got to go so I think we should wrap it up and say thanks very much for your time. It has been extremely useful.