What with Isita getting pneumonia on the hottest day of the year so far and spending the first half of last week at St Mary’s Paddington, and then once she was out taking her and Jamie to Legoland on the weekend, I haven’t had much time to write about NICE’s decision not to fund immunotherapy for high-risk neuroblastoma. This does not affect Isita as she had already started, but it does affect all the children who need the drug but who haven’t started yet. I don’t know how many there are but by the law of averages there must already be about 40 in this country diagnosed since last summer, the approximate cut-off date. It is tragic that they might not get access to this vital treatment.

NICE issued the result of its appraisal of dinutuximab beta on 4 May. A lot of the people who are now more affected by this than we are have protested. Solving Kids’ Cancer – which supports families of children with neuroblastoma – has issued a statement with some other charities. Channel 4 News’ Victoria Macdonald has conducted an extremely moving interview with one family involved.

NICE said that the “plausible estimate” of the cost of the treatment (£62,300-£79,900 per Quality-adjusted life year –QALY – gained) was “much higher than what NICE normally considers a cost-effective use of NHS resources.”  QALYs are the currency of NICE evaluations. Basically, for dinutuximab there isn’t enough evidence of long-term benefit, as the cost is divided by too few years. NICE want to see ten years of benefit.

One of the reasons that this cannot be demonstrated is that the drug is too new. NICE has recognised this – partly – and said that “given the promising clinical benefit shown by dinutuximab beta so far in the trial data and the potential for longer-term data within two to three years… a period of time in the Cancer Drugs Fund (CDF) would be the best opportunity for data collection to address the clinical uncertainties.”

So hooray? Not necessarily. CDF funding would allow doctors to make individual funding requests on a patient-by-patient basis and the NHS would pay so the drug could be trialled over a longer period. But unfortunately, NICE goes on to add that the drug is too expensive even for this.

It has therefore invited the company to make a proposal. In other words, to drop it price. It has come down to a plain haggle. The discussion is no longer about medicine; it is all about money. Can EUSA Pharma, the manufacturer of dinutuximab trim its margins enough to squeeze into NICE’s model? Can NICE be persuaded to widen its criteria so that a hundred or so children don’t fall into a dreadful gap just because they are being treated here in the UK and not in France, Germany, Norway or Spain? The final decision will be issued on 12 June. Let’s not abandon these young lives.

For the past two days, Isita has been at St Mary’s Paddington. We had to go in early on bank holiday Monday as she had a raging temperature. To start with we thought it might be heatstroke, as she had been having the time of her life on Sunday paddling her feet in the swimming pool at her cousins’ house in Surrey. This afternoon they told us that they had identified a chest infection. It may not sound like good news, but it is. Now they can target the antibiotics, and if they work well, there is a good chance she will come home tomorrow.

This was, perhaps, the likely consequence of a fabulous few days of fun and activity, play dates and running about in the garden just like old times. It is easy to forget that Isita is still quite weak and when she is worn out her defences are down. Having said that, we have had the best fortnight since this saga started – happy home life has once again become the norm rather than the exception. The best barometer of our family well-being is how happy Jamie has been the past while. As much as they bicker, they miss each other terribly during the hospital periods.

Isita has the gift of happiness. Even in the hospital she is very happy. In the cooler evenings we have been taking her down the canal to Little Venice, so she hasn’t entirely missed out on the ‘Indian Spring’ or whatever we must call this unlikely heatwave. We haven’t told her that she has a lung infection as she is terrified of the prospect as it takes her back to the infection that landed her up on a ventilator in intensive care last autumn – one of the more petrifying episodes for us too. It is impossible to look at her now and think back to that nadir.

As well as the fact that her hair is now much longer – it is very fine and sticks up in sweet little tufts – Isita no longer has a nose tube. This is big news which I forgot to write about when she had the gastrojejunostomy operation just over a week ago. We had grown used to the ‘NJ’ and anyway she had the enviable ability to look good with a bit of plastic coming out of her nostril. But without it, you can’t tell that there has been anything wrong with her at all. Not until she lifts up her dress and shows you her new ‘peg’ as we call the tube which goes directly into her tummy and also the top bit of her small intestine.

Having the peg put in is a recognition that we are going to be feeding Isita through a tube for a long time yet, but also a confirmation that the feeding is working. If it was a dead loss they wouldn’t have done it. For the first few days Isita was terrified of it. The more you think about it, the odder it is. But, in fact, it is much more comfortable, and we are already seeing the benefits. Without the feeling of the line going down the back of her throat she is swallowing more and even swallowing some food. This is a great small step. It is about a year ago that she went ‘nil by mouth’. Now she puts a lot of food in her mouth but spits most of it out. The more she swallows the closer we are to getting her properly well again.

This evening (Wednesday 25 April) at just after 7.10pm Channel 4 News are running an item on the resolution of the problem of the immunotherapy drug for Isita and the other children currently in treatment. We hope this will help focus attention on the children who haven’t started, and who currently don’t have funding.

This evening (Monday) it looks like a break through has been achieved. I understand that EUSA Pharma has said it will fund the full course of treatment for all children who have started. This is a great relief for us and the other families and we are grateful. Thank you to everyone who helped spread the word. I am sure that helped. We look forward to further enlightened decisions from NICE and NHS England so that all children who need this treatment continue to get it.

Marta and I have been extremely moved by the extraordinarily generous and spontaneous offers of support which we have received since I posted the situation about Isita’s immunotherapy drug. We are currently working through a series of options. But please be reassured, if we need to call for any other kind of help we will certainly do so. Right now, for the sake not just of Isita but for all the other children involved we need to make sure that as many people as possible know what is going on, so that the requests we have for the government and the NHS are heard, understood and acted upon. So our request is that you forward this statement, or a link to this blog, to anyone whom you think could help, and that you post it, tweet and retweet it on social media.

Three requests for the government and the NHS

22 April 2018

In early January 2016, our daughter Isita, now aged six, was diagnosed with stage-four neuroblastoma, a rare and difficult to treat cancer which develops out of neural crest cells and affects about 50 children in this country each year. For the past 16 months she has gone through a difficult and sometimes extremely painful complex of treatment. She has spent much of this time at Great Ormond Street Hospital in London, where the care she has received has been exceptionally good.

Until late last year, all children in the UK diagnosed with high-risk neuroblastoma were given as part of their care a drug called Dinutuximab Beta, an artificial antibody which destroys neuroblastoma cells as if they were viruses. This immunotherapy treatment is vital in reducing the chances of relapse – the event feared most by every parent. The drug was given as part of a clinical trial, which Isita was included in until complications meant she no longer qualified.

In early February, Isita became the first of a new cohort of children to be given this drug outside the trial. The individual funding requests submitted to the NHS by the oncologists at Great Ormond Street for every child were refused and so EUSA Pharma, the company which manufactures the drug, agreed – on compassionate grounds – to supply it for free at its own cost and risk. Isita has now had two out of the five cycles which are necessary to complete the treatment.

On 11 April, EUSA Pharma delivered a dossier of evidence to the National Institute for Clinical Excellence (NICE) which will be used to decide whether the NHS will fund the treatment as part of its standard of care for treating high-risk neuroblastoma. Last Thursday – a few days after NICE accepted the dossier – my wife and I and the parents of four other children also receiving this drug at GOSH were called to a meeting with our children’s doctors who relayed the news that the company can no longer supply this drug for free. We do not blame it for this decision. The hospital has enough supplies to finish the current 10-day cycles being administered to the other children in Isita’s group. From then on, the drug will only become available on the NHS once more if NICE decides that it should be funded. It may take several weeks to issue its decision. Children around the country will soon be affected as other hospitals also run out.

This raises a prospect which the doctors say they have never previously encountered in paediatric medicine: the cancellation of vital treatment in the middle of its administration, not because it is ineffective or too dangerous, but because there is no money for it. We do not believe that this is in any way intended, nor that it is a precedent that the NHS or the government would wish to let stand.

We understand that NICE has an unenviable task, and that none of the funding requests that it has to adjudicate between are trivial. So, our first request is that it decides as quickly as possible to relieve our present uncertainty. Clearly, we would prefer the certainty that the drug will continue to be provided, to the certainty that it won’t. But if it is to be the latter, the sooner we know, the sooner we can try to organise alternative funding. Ideally there should be a three-week gap between the end of one cycle and the beginning of the next. Some delay is possible, but time is not on our side. This is not just important for the children currently receiving the drug, but for those who would normally have expected to start in the next few weeks, and for any child now diagnosed or about to be diagnosed with neuroblastoma. In the worst case, a lot of fund-raising will be necessary.

Our second request, to NICE, but also to the Secretary of State for Health Jeremy Hunt is to pay particular attention to the cruel position in which those children now getting the drug have been left. If NICE’s decision is positive no harm will come, but if negative, the chances of finding replacement funding for all the children in mere weeks are not good. The arguments for compassionate funding to prevent these children from being abandoned are surely very good.

Our third and final request is that the Secretary of State and the Government take note of the fact that the immunotherapy our children have been getting until now is part of the standard of care for treating high-risk neuroblastoma in the United States. We understand that everywhere else in Europe, health ministries routinely approve individual funding requests for this drug. Now that it has all the facts, we know that NICE must decide this question on the rational basis that underpins all its decisions, and that it must make the best of the resources at its command. But it is nevertheless the case that a negative decision would place the NHS’s standard of care for neuroblastoma at a lower level than in most nations we would like to compare ourselves to.

Isita’s treatment is going well. She is most likely going to be discharged tomorrow (Friday) evening. But out of the blue our worry has switched from how to get her out of hospital to how to get her back in again. She and a handful of other children with high risk neuroblastoma who are at approximately the same stage have landed in the middle of an extraordinary and probably unprecedented muddle. The NHS may have to suspend the immunotherapy which they have been getting for the past couple of months.

It is, of course, usual for the NHS to provide some drugs and not others on grounds of cost-effectiveness. It is very unusual, however, for it to have to stop providing a life-saving treatment in the middle of its administration on financial grounds. The senior consultant oncologists who have just informed us of this development said they believed it has never happened before in paediatric medicine at least.

This afternoon, the doctors gathered together the parents of all the affected children in a seminar room on the ward. We all know or recognise each other as several children are on the ward at the moment, and others have been here in the past few months. Ours are the first to get to the immunotherapy stage since a clinical trial under which everyone received the treatment ended last year. Isita was enrolled on that trial, but the problems she encountered after high-dose chemotherapy meant she dropped off it.

The news which the doctors had for us was that EUSA Pharma, the company which manufactures the Dinutuximab Beta anti-GD2 antibody can no longer provide it for free. As the decision whether or not to provide it on the NHS is still pending, no further supplies of the drug are available. Those who are getting it right now (like Isita) can finish their current cycle. But we don’t know if the next cycle  will be provided, or if eventually we will have to pay for it ourselves one way or another.

EUSA Pharma has been very generous. At its own risk and cost it has covered the provision of Dinutuximab following the end of the clinical trial. If it had not done this, no drug would have been available to any child in this cohort at all. This has been a substantial undertaking. So if EUSA cannot afford it any more, we cannot blame it. The worst thing for us and the 50 or so children who are diagnosed with high-risk neuroblastoma every year would be for this company to go bust. No one else makes the drug.

The results of last year’s clinical trial were presented to the National Institute of Clinical Excellence (NICE) last week. This is the body which decides what the NHS will pay for and what it won’t. The doctors have said the numbers should support the provision of Dinutuximab on the NHS as standard of care. It is standard in the United States. Elsewhere in Europe individual requests for government funding for the drug are routinely approved.  It would be a shame if this standard were not available to children in the UK.

We know that NICE does not appreciate external pressure on its decisions and that it has to weigh up a lot of different priorities. We are not attacking it. The problem right now is the sudden introduction of great uncertainty at a crucial moment of treatment. The institute could take six weeks to decide, while Isita is next due the drug in three weeks.

The best result would be a speedy approval. Next best would be an approval causing a delay of only a few weeks. Third best – for us at least – would a compromise which allowed those children who have started the antibody treatment to go all the way through to the end even if no new treatments are funded. And worst of all would be no funding at all.

We hope and pray that they make the right decision for us and for everyone involved. In the meantime, we are heading home for some serious baking.

Isita started the second cycle of immunotherapy on Thursday. As she sailed through the first cycle without major side-effects, we hoped that it might be even easier this time. But she immediately developed a persistent dry cough.

Somehow, the antibodies provoke a tightening of the airway. They are giving her regular doses of adrenaline through a nebuliser – a bit like treating asthma – and also piriton,which makes her sleepy. Each time the cough gets too much, they reduce the dosage of antibodies to one-eighth and slowly build it up again over a day, so that her body can gradually acclimatise to their effect. For the past three days she has had, on average, one quarter of the full dose. So she will certainly be in hospital for a fortnight or more, rather than just 10 days.

While we are keen to spend as much time as possible at home, this is far from the top priority. It is much more important that she completes this cycle and is fit to do the third, fourth and fifth as well.

Looking on the bright side, this cough is a fairly common side-effect and the specialist nurses have experience at dealing with it. Also, there is no sign of the more serious and distressing problem of neuropathic pain. We pray to avoid that entirely.

It is hardly surprising that this amazing medicine is having some unwanted effects on Isita’s body in addition to its incredible benefit. What she is being given is a drug called Dinutuximab. In scientific terms this is a “chimeric human-murine anti-GD2 monoclonal antibody”.

This needs some unpacking. The chimera (I just looked up on Wikipedia) is a portmanteau beast of ancient Greek myth – a lion, with a goat’s head sprouting from its middle and a snake’s head tail. Well, the magical monster we are injecting into Isita is half-human, half-mouse – not an obvious combination to inspire dread or wonder, but miraculous nevertheless. In the way that a regular antibody’s job is to gobble up a specific virus, this wee sleekit tim’rous cowrin’ beastie gobbles up neuroblastoma cells, identified as they are by a protein called GD2. I think monoclonal means that all the antibodies were cloned from a single parent cell.

Similar antibodies are now being used to save the lives of people with all kinds of cancer. We are fortunate that it is available for Isita as the gravest threat for her is that a new tumour should now appear. If this were to happen it would not come from the original tumour, which we hope is all but dead, but from neuroblastoma cells at large in her body that have survived chemotherapy and are therefore immune to it. Such a relapse would be very hard to treat. If any such devil cells exist, mouse-man is out to kill them.

Isita is very well and so are we all. This is a great thing to be able to write. I have been meaning to put it down in words, to catch up on this blog evening after evening, but the days slip by. We have spent an entire week at home after a 10-day stretch in hospital for the first session of immunotherapy, which went better than we could have hoped. We are catching our breath and even beginning to dare to hope.

Today we haven’t stirred from the house and it has been wonderful. In the morning after we had eventually got up we played Ludo and then ‘What’s the time Mr Wolf’ and then ‘Un, dos, tres, pollito Ingles’  which is the Spanish version. In the afternoon we watched a movie. Then Marta and Isita fell asleep on the sofa. Isita is sleeping a lot (so is Marta to be honest). We are recovering after a year of exhaustion.

Not that we are finished with medical things, even during these lovely periods away from the hospital. The day starts early with a handful of medicines that we have to put through Isita’s NJ tube: a couple of things to reduce nausea, gabapentin, which she will have for the next six months to minimise the effect of neuropathy, sodium bicarbonate to correct the acid level of her blood as her kidneys are still not working perfectly, and cis-retinoic acid – a kind of vitamin A which prompts neuroblastoma cells to differentiate into normal healthy cells.

We can’t put them all through at once. By the time we have also taken down her paraenteral nutrution, put on vitamin E cream to mitigate the drying effect of vitamin A on her skin and organised a milk feed, a good three or four hours have passed and it is time to take her to school. She goes for a couple of hours in the week. There are more meds in the afternoon and the evening.

Marta and I are both working, so you can imagine, there isn’t much time for anything else even though we have some wonderful help. The period of the amazing aunties who spent so much time looking after Isita while she was in hospital is gradually drawing to an end as Isita gets better and her needs change. Of course we still need help, and quite soon we should be getting some professional nursing assistance to take away some of the stress and pressure of giving the medicines.

The most important thing is that we are spending time together as a family. As we have spent more time at home Jamie has begun to speak more about the strain that he has been under. The poor boy has been struggling with feelings of isolation and loneliness, which sometimes prevent him from sleeping. One of the positive ways that he has dealt with this is voracious reading; less positive has been equally voracious use of the iPAD. It is now obvious why he sometimes has such tantrums when we take it away from him. It is going to take a long time to get things back to normal, but we will succeed.

They started the antibodies at about midday on Monday. So far Isita is tolerating the treatment much better than we feared. She has had some stomach cramps and a bit more diarrhoea than usual. She’s having extra fluids and will get a blood transfusion as she is a bit pale. But crucially she is not suffering the acute neuropathic pain that is one of the worst side- effects. They are keeping a very close eye on her, both clinically and crunching the numbers. Pray God nothing more complicated comes up.