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INSIDE HEALTH

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Programme 2Ìý – Welsh patient power, Liquid biopsies, Food allergies, Dosing errors

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TX:Ìý 20.09.16Ìý 2100-2130

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PRESENTER:Ìý MARK PORTER

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PRODUCER:Ìý FIONA HILL

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Porter

Coming up in tonight’s programme:Ìý Liquid biopsies - the new blood tests that can pick up tell-tale traces of cancer and help find the best treatment.

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Clip

Cancers change through treatment and we can’t keep repeatedly biopsying patients.Ìý But why we’re really excited about these liquid biopsies is we can repeat blood tests regularly, so we can actively follow what’s happening in the cancer as we treat it and make sure we’re adjusting the treatment most appropriately.

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Porter

And the latest research on food allergies, turning recent infant feeding practice on its head.

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Clip

Food allergy wasn’t really a common problem 30, 40 years ago.Ìý And food allergy’s now one of the commonest health conditions in young people in developed countries and it’s seen as a major public health problem, so we’re really studying it actively and this discovery that the way we feed babies may influence whether you get food allergy or not is quite exciting.

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Porter

But first a new initiative from Wales that struck a chord here at Inside Health. Choosing Wisely Wales encourages patients to take a more active role in decisions about their care amid concerns that the NHS is often too quick to offer treatments and interventions that don’t always benefit them - and may even harm them.

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Patients will be encouraged to have open and honest discussions with those advising them, and to ask four simple questions:

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What are my options?

How likely is the treatment to benefit or harm me?

Do I really need it?

And what can I do to help myself?

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Dr Paul Myers is Chair of the Academy of Medical Royal Colleges in Wales and is leading the new initiative.

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Myers

What we’re hoping by giving patients the confidence to be a little bit more assertive in conversations with their clinicians and posing some questions of their clinicians when treatments are recommended and balancing that with clinicians who are prepared to accept that increased competent patients and start more open sharing of the risks and benefits of treatments and tests.

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Porter

So this is a way, if you like, of making healthcare professionals think twice about the appropriateness of an investigation, of a treatment.Ìý I mean what drives that?Ìý Do we know that we’re doing things inappropriately or perhaps potentially harmful to our patients?

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Myers

Well I think we know that perhaps possibly up to 10% of interventions in healthcare are inappropriate and sometimes even harmful.Ìý And that probably doesn’t need to be the case.Ìý We know that a lot of patients continually are expressing that they’d like to be more involved in the decisions made about them.Ìý Clinicians, I think, are increasingly driven by guidance and protocols and worry about deviating from those…

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Porter

The tramlines rather than guidelines.

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Myers

The tramlines rather than guidelines – absolutely.Ìý And we’re asking clinicians to start identifying patients’ preferences.Ìý It’s interesting that over – over the last few years we’ve been told we must concentrate on needs, needs, needs and not wants but actually if we don’t know what the wants of patients are and we don’t specifically address them – I’m not saying we need to meet them – but if we don’t know what their wants and preferences are actually we’re often going to end up with dissatisfied patients.

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Porter

Well listening in our Glasgow studio is Dr Margaret McCartney.Ìý Margaret, is something similar happening in Scotland, because this isn’t the first time that there’s been this sort of campaign is there?

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McCartney

No and of course Wales have pre-empted themselves really with prudent practice a couple of years ago, in Scotland we’ve got this realistic medicine, the report by our CMO.Ìý And really I think they’re getting towards the same thing – stop doing things that don’t work, try and make sure we’re offering things of value to patients and talk about the pros and the cons of interventions.

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Porter

Paul, you’ve highlighted in Wales a list of five commonly used interventions, tests and treatments, that you deem to be possibly of low benefit that you want to make a priority for this campaign, I mean it includes things like scans and x-rays for straightforward back pain.Ìý In the very frail and terminally ill careful about considering long term medicines, I presume that’s things like statins and blood pressure treatments and all those sorts of things that we have people on.Ìý Why have you come up with this particular list, what were the drivers behind that, is this – because one could look at that and say well this is a cost-cutting exercise possibly?

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Myers

It’s not a cost-cutting exercise, it is about value but it is primarily about patient safety.Ìý And I think what we found out in Wales when we’ve started talking with our patients actually they are more interested in a shared decision making, rather than the reduced list.Ìý So in many ways in Wales, while I’m certainly happy to address and will do the six areas we’ve identified, actually what we think is more important is that shift in balance in the conversation, so we’re actually going to concentrate more on trying to have more equal conversations and more open and honest conversations.Ìý And these, if you like, are the tools to help our clinicians do that.Ìý Some patients do tell us they do have difficulty having conversations with some clinicians and there is still an atmosphere of doctor knows best, when we’ve asked patients they say oh the doctor knows best, I’ll rely on whatever the doctor says.Ìý It isn’t just about doctors, it’s about all clinicians across the board.Ìý So I think assertiveness is quite a strong word but to be more confident I think in questioning and discussing.

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Porter

Perhaps less passive is what we’re saying rather than overly assertive.Ìý But I must say looking at the questions, just raising the issue, Margaret, you must approve of this…

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McCartney

Oh definitely, I think the questions are great – you know discuss with your doctor what would happen if I did nothing, what do I really want to get out of this, will this give me what I want – definitely that’s what we want.Ìý And actually the recommendations that have been chosen in Wales are great, I think they’re really good because they’re quite subtle.Ìý It says things like – transfusion is not usually needed for certain blood figures, scans and x-rays aren’t usually indicated for low back pain – so there is obviously a bit of common sense being applied or a bit of clinical expertise and thoughtfulness, it’s not just a binary – do this or don’t do that.Ìý But what are the cultural problems, what are the systematic problems that cause things to run the way they are?Ìý So, for example, I would love to have proper time to discuss things with my patients, so if someone comes in and they’ve got four interrelated things that they want to discuss how can I possibly get through that with a degree of quality in 10 minutes?Ìý It’s absolutely absurd.Ìý If someone is unable to read very well and is unable to read any of the information sheets or shared decision making websites how can I really make sure that that person knows what they’re doing when they’re trying to make a decision?Ìý So it’s these big system problems I think we have to deal with as well – why have we got a situation where doctors are afraid to gear off guidelines because people are afraid of being sued.Ìý So these are the other big things that we have to tackle and think about and I’m just afraid that we get side-lined into thinking this is going to sort everything when actually there’s a huge amount of problems in the way we’re practising medicine today.Ìý We need to tackle this much more broadly.

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Myers

You identify two areas that are sort of very much coming back to us and were not surprises.Ìý One is around about litigation and clinicians being sued when patients make a decision and then that turns out to have an adverse outcome, the patient gets harmed.Ìý And also the issue of time.Ìý We absolutely recognise time but I think what we’re trying to suggest is that if you spend time in the initial consultation actually listening and identifying what the concerns and the values and the preferences of the patient are that actually pays dividends later on.

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Porter

Paul, what happens next, what are patients in Wales likely to notice and when?

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Myers

Okay.Ìý We’re calling this a movement rather than a campaign, we do not want to do things to people, we want to do things with people and one of the next steps we’re doing is going out into communities and getting together with groups of patients and saying how would you like to take this forward, how are you going to gain the confidence to do this.Ìý We don’t want to go out and train patients as such, but we do want to work with them to help them to be more assertive and have more confidence and be more questioning or less passive, to use your words, that’s perhaps a kind of way of putting it.Ìý But we do realise from the international experience that actually to produce a major culture change like this could take two or three years.

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Porter

And I know you only speak for Wales but we’ve heard what’s happening in Scotland but are there similar plans happening elsewhere in the UK that you’re aware of?

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Myers

Yes there will be a UK system that’s going to be launched later in the autumn.

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Porter

Dr Paul Myers and Margaret McCartney thank you both very much. There are more details on the initiative on the Inside Health page of the Radio 4 website.

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Breakthrough and game changer are much abused terms in the hype that so often surrounds advances in the field of cancer. But sometimes they are justified and I have a feeling our next item may qualify.

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Liquid biopsies are a revolutionary new approach to managing cancers. Instead of taking a conventional sample or biopsy from the bulk of a tumour, liquid biopsies use a blood test to detect cancer DNA that has leached into the circulation.

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To find out what is involved, and to glimpse into the future of a technique that is exciting cancer doctors across the world, I went to the Royal Marsden Hospital in London to meet one of those pioneering liquid biopsy. ÌýDr Nick Turner is a medical oncologist with a special interest in breast cancer, and team leader at the Institute of Cancer Research.

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Turner

A liquid biopsy is a way effectively of getting a biopsy of the cancer just from a blood test.Ìý For many patients with cancer they have a biopsy not only to confirm the diagnosis but to get lots of information about the cancer that would be useful to guide treatment.Ìý Now in many situations it’s just not possible to biopsy a cancer and what we really want to develop is blood tests that will give us the same information.

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Porter

So a conventional biopsy would let’s assume we’re putting a needle into the tumour but some cancers are very difficult to access.Ìý But I think people would understand it’s quite easy to take a sample if you’re sticking a needle into something but how can a blood test sample a tumour that could be three or four feet away from where you’re taking the blood sample?

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Turner

We now know that cancers shed their cells into the blood and they also shed their genetic material, their DNA, into the blood and we’ve now developed very sensitive tests that allows us to analyse the cancer from this DNA that the cancer sheds into the blood.Ìý And we can now very accurately from a blood test work out the mutations that are in the cancer that are causing it to grow.Ìý And why that’s important is for many of these mutations we now have treatments that specifically target those mutations.Ìý So from a liquid biopsy we can potentially work out which treatment is right for which patient.

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Porter

But surely all of the cells in our body are discarding bits of genetic debris into the blood, how do you spot this tiny little trace of the cancer?

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Turner

Mark, that’s a very good point and the reason it’s taken a while to develop these blood tests there’s been technological advances that has allowed us to pick up the tiny amount of cancer DNA amongst the normal DNA that there is in the bloodstream.Ìý And technology has advanced to the point where we can be really confident that we’re analysing the cancer DNA there, even though often it’s only a small amount of the DNA present.

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Porter

What does that DNA from the cancer tell you, does it tell you what type of cancer it is, does it tell you where it is, does it tell you how aggressive it is, what sort of things can you learn?

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Turner

Well at the moment the most useful ways are it identifies the mutations that have occurred in that cancer’s DNA that have caused it to grow.Ìý And why that’s important is that for many of those we have treatments that work probably only in cancers that have the mutations and so with the blood tests we can identify what’s gone on in the cancer and target the treatment.

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Porter

But you can do that with a conventional biopsy, assuming you can get a sample of the tissue, so the liquid biopsy doesn’t add anything from that perspective?

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Turner

Well look I think it does, you’re right, when we can get a biopsy but frequently patients can’t be biopsied because of where the cancer is and it’s very challenging.Ìý But why a liquid biopsy is very important is cancers change through treatment and as we treat the cancer it changes and the mutations that are driving it can change and we can’t keep repeatedly biopsying patients because that’s just impractical and also not safe for a patient.Ìý But why we’re really excited about these liquid biopsies is we can repeat blood tests regularly.Ìý So we can actively follow what’s happening in the cancer as we treat it and make sure we’re adjusting the treatment most appropriately.

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Porter

How sensitive are these tests in terms of picking up signs of trouble?Ìý I mean are you able to use a liquid biopsy to detect problems that you would never be aware of if you were using conventional testing?

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Turner

Well we are starting to develop liquid biopsies to try and pick up very small amounts of residual cancer after treatment.Ìý The key question for many women who’ve been treated for breast cancer, in fact for any cancer, is am I cured or is there a risk of relapse.Ìý And some very exciting studies are now coming up that we might be able to use these liquid biopsies to pick up tiny amounts of cancer DNA that show a cancer is still there.Ìý And why that’s important is then we can target treatments to those patients to try and prevent relapse.

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Porter

And are these biopsies actually being used in day-to-day clinical practice now and if so for what sort of cancers?

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Turner

They’re really pushing on the door of being used in routine practice for patients with lung cancer.

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Porter

And this is both a common and a serious cancer but it’s also quite a difficult cancer to get samples.

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Turner

Yes exactly and that’s the situation which is most relevant, Mark, that many patients with lung cancer it’s very difficult to get a sample for molecular analysis.Ìý Now I treat patients with breast cancer and we’ve got a very large study that we’re opening up called Plasma Match where we’re going to be taking blood samples from a thousand women with breast cancer and in this study we’re really going to try and show that these blood tests are really useful for women with breast cancer.

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Porter

Amanda - a patient of Nick Turner’s at the Marsden - was diagnosed with breast cancer in July 2012.

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Amanda

When I came in they mammogramed me, biopsied me and diagnosed me on the same day.Ìý But before then I still didn’t believe it was cancer because there’s no cancer in my family, so I just thought I must have had some huge infection in my boob.

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Porter

Were you told immediately what it was and what it would entail?

Amanda

Yes, they said that it would be chemotherapy, probably radiotherapy and because it’s so large probably a mastectomy.

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Porter

When was the subject of liquid biopsy raised?

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Amanda

When I came in they asked me whether I would do three studies and a trial and it wasn’t called liquid biopsy, I just knew that they were taking blood.

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Porter

Amanda talks about having lots of blood tests, I presume that amongst those were the liquid biopsies but she didn’t even notice she was having them.

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Turner

So when I first met Amanda in 2014 it was after her cancer had unfortunately recurred and at that point we were developing liquid biopsies and she was very kind enough to take part of one of our studies when she had a biopsy of the cancer in the liver and we also – she also had a blood test at the same time.Ìý And we subsequently showed that the liquid biopsy gave us exactly the same result as her liver biopsy and we identified that her cancer actually had a very rare but very specific mutation in it that was causing it to grow.Ìý Now at that point we were just developing the blood test but we’re now ready to put them into practice and we’re now two years later through the blood tests we can show that her cancer still has the mutation in it driving it to grow.Ìý And we’ve now got a study that’s just about to open up with a drug that particularly targets her cancer and that’s what we hope to then get her on in the future.

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Amanda

In 2014 they discovered breast cancer in my hip and liver and spine.Ìý So I started more chemotherapy and a new trial drug.

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Porter

You look remarkably well at the moment…

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Amanda

I am well, I’ve had no symptoms…

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Porter

You’re coping very well.

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Amanda

Because I was on the trial they picked up the secondaries and it turns out I’m tough as old boots, so I dealt with the chemotherapy and radiotherapy really well.

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Porter

So Amanda’s been involved in this from the beginning, effectively, and is now potentially we hope starting to reap the rewards.

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Turner

Exactly, so Amanda’s helped us originally develop the test and now I’m quite excited that we’ll be in a position where hopefully we’ll be able to get her to benefit from very kindly donating her blood tests to us in 2014.

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Porter

Looking forward, assuming everything progresses as smoothly as you would hope, I mean is this the sort of thing that one day might be used as a test for cancer in the very, very earliest stages, and can you envisage a day when people are having blood tests to look for cancers?

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Turner

We’re really peering into the future here and I think even if it works it’s going to be a long time till it comes through.Ìý But actually people are beginning to ask that question.Ìý We know the liquid biopsies can be very good at detecting cancer when we know it’s there but could we use these concepts to screen for cancer in the first place?Ìý Could we find signs of cancer in the blood tests and use that information to then target that patient for screening to find out where the cancer is?

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So looking into the future and the potential for these blood tests is I think quite exciting.

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Porter

Quite exciting indeed! A cautiously optimistic Nick Turner talking to me with Amanda at the Royal Marsden Hospital.

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Now to a new development in a story that we have been following for a couple of years. Conventional wisdom has it that delaying the introduction of foods like peanuts, fish and eggs during the weaning of babies reduces the risk of food allergies later in life. But recent research suggests that the opposite may actually be true - that earlier introduction may protect against such allergies.

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We reported on this last year when the LEAP study found that feeding peanut based foods early, rather than delaying exposure to them, protected children from developing peanut allergy. And now a team at Imperial College London has analysed data from 146 studies involving over 200,000 children looking at the timing of introducing potential allergens during weaning, and what impact that has on the risk of allergies and related problems.

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Dr Robert Boyle is Director of Imperial’s Paediatric Research Unit. So what did they find?

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Boyle

If you introduce common allergenic foods, certainly egg and peanut, into a young baby’s diet earlier rather than later then that will reduce their risk of developing egg or peanut allergy.Ìý The effect is quite specific to the given food – so introducing egg early reduces risk of egg allergy, introducing peanuts reduces risk of peanut allergy.Ìý The effect is quite strong.Ìý So for egg we found approximately 40% reduction in risk of egg allergy if egg is given at four to six months rather than later and for peanut we found approximately a 70% reduction in risk of peanut allergy if peanut is given between four and 11 months rather than later.

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Porter

What about other allergens like dairy for instance, a common problem?

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Boyle

Yes, so for milk, fish, gluten there weren’t enough studies or there weren’t enough data in the studies to really yield conclusive answers.Ìý So the jury is still out on whether this applies to all foods.Ìý Interestingly it doesn’t seem to apply to celiac disease, which is a sort of wheat allergy or a type of gluten allergy, but one which occurs through different immune mechanisms to egg and peanut allergy.Ìý So for celiac disease whether you introduce gluten early or late doesn’t seem to influence whether or not you get that particular condition.

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Porter

And when you say the research what you actually did was go looking at all the available evidence.

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Boyle

Yes we reviewed all studies that have been published up until this year which have evaluated the relationship between timing of allergenic food introduction in a young infant and immune conditions.

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Porter

Some listeners may be surprised by that conclusion because I mean the standard advice, up until quite recently, has been that we should be avoiding these types of foods and delaying exposure and that was deemed to be somehow healthy and to protect against allergy.Ìý So how did we get it wrong?

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Boyle

Well it was a best guess when the advice was introduced to actively delay the introduction of allergenic foods some years ago.

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Porter

So it wasn’t actually based on a lot of evidence at the time.

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Boyle

It wasn’t as strong as the evidence base is now.Ìý We’ve known for over a hundred years that in animal experiments if you feed an animal chicken’s egg it’s then very difficult to make that animal allergic to chicken’s egg.Ìý So the proof of principle has been there in science for over a hundred years, it’s only really in the last 10 years that people have actively tried to do randomised control trials, intervention studies, in humans to see whether this principle is relevant to human health.Ìý And part of the reason for that is that food allergy, which is the disease which is relevant to this question, food allergy wasn’t really a common problem 30, 40 years ago, it wasn’t thought to be so the scientific literature on food allergy was quite small, food allergy clinics were small and infrequent and food allergy is now one of the commonest health conditions in young people in developed countries and it’s seen as a major public health problem.Ìý So we’re really studying it actively and this discovery that the way we feed babies may influence whether you get food allergy or not is quite exciting with a view to prevention.

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Porter

If you’re a sceptic you might argue that one of the reasons that food allergy is more common now is the advice that we’ve been giving people to avoid these allergens and delay exposure.Ìý I mean might that have been a factor, we got it quite wrong didn’t we?

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Boyle

It’s certainly true that people give at present peanut and some other allergenic foods quite late to infants, so they don’t feed them to infants early on and the previous advice, public health advice, may have influenced that behaviour.Ìý But I think it’s hard to lay the full blame – we don’t really know why food allergy’s getting more common, it’s hard to put all of the blame for that at the feet of the public health bodies.

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Porter

And can you put that into context?Ìý When you’re talking about introducing early what sort of timescale are we talking about?

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Boyle

In the studies egg was introduced between four and six months of age in the early group and peanut between four and 11 months of age.Ìý At present the Department of Health advice is that – and in fact World Health Organisation advice – is that all infants should just be breastfed for the first six months of life.Ìý So there is ongoing Department of Health work happening where people are looking at this question of whether food such as egg and peanut should be introduced before six months.

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Porter

We should be clear about – when we’re talking about peanuts – that the idea is you’re not talking about giving babies whole peanuts when they’re four months old – peanut containing foods we’re talking about.

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Boyle

That’s right.Ìý So in the studies people mainly used peanut butter in peanut studies and mainly used egg powder with soft foods.Ìý But yes chunky foods are not a good thing in young babies due to the choking hazard.

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Porter

We may not fully understand the mechanism of action but what’s the current theory as to why or how this might help?

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Boyle

The part of your immune system which is in the intestine has a tendency to tolerogenic immune responses, that means immune responses which don’t result in inflammation.

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Porter

So it’s seeing something and recognising it as a friend rather than an enemy.

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Boyle

That’s right.Ìý So obviously we put so many different things into our mouth and there are so many organisms living in our gut that if the immune system in the gut was very aggressive and overactive that would result in a lot of health problems.Ìý So in general the immune system in our gut is good at recognising things and deciding not to react to them.Ìý So it seems that if you’re exposed to egg and peanut through the oral route then that makes your immune system likely to tolerate those foods, if you’re exposed in other ways and not via the oral route then you’re more likely to be allergic.

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Porter

And if we delay that exposure might it be that the gut is then more likely to see this newcomer as a stranger that needs to be treated with caution?

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Boyle

Exactly.

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Porter

Dr Robert Boyle and there is a link to his study on our website.

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Continuing the paediatric theme, another paper that caught our eye this week was an experiment to see how good parents are at measuring children’s liquid medicines. Each parent was asked to measure out nine doses using a small graduated cup, or one of two syringes, and assess as to how accurate they had been. Well the results weren’t that great - 84% of the 2,000 or so volunteer parents made at least one error, and remember they only had to do this nine times, and 20%, that’s one in five, made at least one big error. Inside Health’s Margaret McCartney has been taking a closer look. ÌýMargaret, that’s a lot of mistakes particularly when they knew they were being tested.

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McCartney

It’s certainly concerning and given the amount of concerns that parents already have about giving their children medication I think most folk will be a bit worried to think oh am I getting this somewhat wrong, especially when we don’t know that we’re getting it wrong, that’s the other big problem, these are often hidden errors I think.

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Porter

One of the things that stood out for me was the researchers looked at the differences between cups and syringes, syringes came out as being very good, and actually we’ve been using syringes for some time haven’t we, routinely with liquid medicines for children?

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McCartney

Yeah the medicines and healthcare regulatory authority did say in 2011 that we should make the move over to syringes because they did seem to be more reliable for parents measuring out medicines for their children.Ìý And I think that is to a huge extent happening, although I do remember having bought paracetamol for my children in the not too recent past and finding it was just a bottle.Ìý There’s also sachet measurements that come as well which are quite good because that’s pre-measured for you, so hopefully less likely to make mistakes.Ìý But the big differences was between using a cup to measure and a syringe, syringes just seemed to be much more reliable.

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Porter

So what were the take home findings for this study for you, I mean where are parents going wrong?

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McCartney

The striking thing is that it’s easy to make mistakes and this randomised control trial was done without an ill child in the background, so it was done in the kind of placid surroundings of a GP’s surgery or an outpatients’ department, it wasn’t done when you’ve got an unwell child which you would hope would mean that you would have less errors in that situation.Ìý So I’m worried actually the real life scenario might be that we’re making more mistakes than that.Ìý So mistakes are really common and often quite frequent and sometimes are quite large.Ìý So I suppose the first thing is to know that it is easy to make a mistake about doses.Ìý And the second thing I think would be to really use a syringe if you get the choice to use a syringe and make sure you know what it is that you’re measuring and what the dose should be for your child.Ìý And the other thing to remember is pharmacists are your friend, fantastic source of information over-the-counter and they will help you to make sure we’re doing it properly.

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Porter

Thank you Margaret. I am reminded of the carpenters’ mantra - measure twice, cut once.

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Just time to tell you about next week when I meet a man who seriously considered amputating his own arm to gain some relief from complex regional pain syndrome. And baclofen and alcohol - we report on the latest research on a new use for this long established muscle relaxant - could it help people with a serious drink problem?

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ENDS