Taking care of business

The brash banking centre of Canary Wharf, with its gleaming sky-high towers, is the unlikely location for the headquarters of that most decorous of institutions, the European Medicines Agency.  Standing between the murky waters of the Thames and Barclays HQ, the EMA gleams like a beacon for health rather than wealth, right in the heart of London’s bonus-driven business district.

The business I was to witness there, though, was of an altogether different kind. The Paediatric Committee (PDCO) of the EMA had invited me to observe them reviewing investigations into children’s medicines that were being conducted by drug companies. It was illuminating to see the Committee rigourously holding a Pharma company to the conditions that had been set for a trial into a paediatric cancer. What was more interesting, though, was to hear an explanation later of the amendments to regulation the EMA had made in the summer and whether these would, as some members of Pharma had suggested, dramatically change the volume of commercial research into young people’s  cancers.

 In June 2015, an EMA press release announced the revision of some of the class waivers that had allowed companies to avoid obligations to seek cures for childhood illnesses, particularly cancer. Representatives of some drug companies had claimed that this changed the whole research landscape and their employers might even abandon waivers altogether.

The explanation given at the EMA, however, was less dramatic. Removal of some of the broad class waivers would engender more research, particularly for illnesses, such as liver cancer, which occur in both adults and children. However, companies could still apply for product specific waivers. As a recent letter to Lancet Oncology stated ‘ if the company decides to request a waiver because the illness does not exist in children, even though the drug's mechanism of action is relevant for paediatric malignancies, EMA cannot force the company to assess a drug in children.’

 This is not something that can be changed by the EMA in London. It can only be resolved in Brussels at the Commission, where the process of European law begins. For this reason, over the autumn, the parents campaign group, Unite2Cure, has been exchanging letters  with the European Health Commissioner, with the support of two MEPs: from Britain, Glenis Wilmott, and from France, Francoise Grosstete.

In January, we will be visiting Ms Wilmott at her surgery in Nottingham at a meeting that will hopefully prepare the ground for the annual Cancer Drugs Development Forum conference on paediatric medicines that will be held later that month. CDDF delegates will be mindful of the 10 year review of the Paediatric Medicines Regulation due in 2017 and for which consultations are already being prepared.

It would be good to think that 2016 will be the opportunity to repair the weaknesses in the Regulation that were identified soon after its introduction. However, the tone of the replies we have received from the Commission suggest they may prefer business as usual to any fundamental change. There is of course no way of telling what the outcome will be in 2016 or 2017, but it would be wise to take the opportunity of January 1^st to make some firm resolutions.

Happy New Year.

Just like Jericho

‘Just heard about this petition at the 3rd European Bone network Meeting. The power of people, patients and their advocates is the way forward to change this law and get access to new drugs for children/TYA with cancer... I hope I have set up a train of emails in my department for all my colleagues to do the same’

Bernadette Brennan, Consultant Paediatric Oncologist, UK

This is one of the thousand plus positive responses to the online campaign we ran during September, Childhood Cancer Awareness month. The idea was cooked up by five of us over the dinner table at the Childhood Cancer International conference in Sweden in May. Three months later, our website went live calling for ‘basic changes to European Law to speed up access to newer, kinder and potentially better drugs for more children and teenagers with cancer.’

E-petitions are of course ten a penny but our intention has been to use support garnered over September to demonstrate that there is a real desire for change within the childhood cancer community and to take this as ‘ammo’ when we push for reform of the Paediatric Medicines Regulation in the months ahead.

My belief is that the quality rather than the quantity of the support posted on the website gives our campaign its credibility. Major international networks like SIOPE and ITCC have signed up and, of equal value, grassroots organisations have recognised the relevance of the campaign to the ordinary families they represent. The big names of paediatric oncology have been willing to give their celebrity endorsement but what for me is equally telling are the messages from the carers and survivors of the desperate need for change.

Ida Borhan, Manager, Malaysia: “My daughter Irdina lost a battle no child should endure, let alone lose.”

 Krystal Jones Mother USA:  “Our children need a fighting chance! They need treatments that will work but without paying the cost of their lives from it. No parent should ever have to bury their child. There has to be a better way!”

 Fabrizio Allavena, Italy: “A child’s life is a piece of our future.”

 Debbie Jansen, USA: “Pediatric cancer needs to become an oxymoron.”

 Dragana Radulovic Parent Serbia We (NGO Chika Boca Serbia) believe: all children have unique needs and should grow up without illness. Access to the best possible care for children with cancer is their human right. Every child deserve the best possible treatment and care. One death is too many.

 Anne McLaughlin, Midwife, Australia: “No funding. No research. No CURE.”

 As the messages came in through the last weeks of summer, the reach of these small, unofficial networks into the childhood cancer community was demonstrated. An email to the Serbian punks at Radio Mladice generated a hundred signatures from across the Balkans. The mother of a boy who died of Ewing’s back in the 70s went on Italian radio and for the final week of September, our Wall of Support was plastered in Italian graffiti. 

Where do we take these messages? Well, we’ll be meeting members of the paediatric committee of the European Medicines Agency in November but our first stop was the Cancer Drugs Development Forum (CDDF) in London in the first week of October. CDDF are the platform responsible for knocking the Paediatric Medicines Regulation into shape and the two working group meetings there, though productive, included some surprising revelations. Until the dust has settled and we’ve made sense of what was said, I’ll leave reporting on where the process of reforming the Regulation now stands. 

Get lucky

I’ve just returned from the European meeting of Childhood Cancer International, which this year was held in Malmo, just over the crossing from Copenhagen, the location for the Danish noir thriller, ‘The Bridge.’ CCI is always a heartening experience, a kind of bridge itself for a remarkable set of activists from across the Continent, all the way from from Scandinavia down to the Balkans and beyond. The meeting  was of exactly a hundred people (if you include Sebastian, the baby brought by his mother in a pram) and was made up of parents, carers,  a few professionals and, as  always, a significant number of former patients, usually referred to as the 'survivors’ group. '

It was therefore interesting to hear from a Greek survivor, Aimilia Tsirou, who in her presentation explained that they don’t actually like being called  ‘survivors,’ but that nobody has been able to come up with a better term. This prompted me to make an off-the-cuff remark about the words we use for cancer, something which resulted in more excitement from delegates than the painstakingly prepared PowerPoint  I delivered the following day.

My passing thought was on how cancer tends to be described in the language of warfare. If someone recovers, we say they have ‘beaten cancer.’ If they don't, the  obituary relates how so-and-so has finally ‘lost their battle against cancer.’  These are only words, of course, but my problem is that they affect the way we think about ourselves and that there is an implication here that if a child relapses, it is because they have in some way failed.  

We still know surprisingly little about why a child gets cancer but one thing we know for certain is that it is never the result of something that they did. ‘Attitude’ can, of course, have great significance in health. It can affect how a child settles back into normal life, on the limits they allow disability to place upon them, on the skills they develop, physical, mental or interpersonal. But let’s get real, nobody, whether an adult or a child, ever willed away a tumour.

The broadcaster, Jenni Murray, who developed breast cancer in middle life described her remission this way.

‘Dealing with cancer has nothing to do with battling or fighting or positive thinking. I was fortunate. I had a relatively early-stage hormone receptor breast cancer. It hadn't spread. It's probably the best researched form of the disease. I gritted my teeth, put my trust in my oncologist, tried not to get too depressed about surgery and chemotherapy and, six years on, I'm still here.’

I do not think Murray would object to her words being paraphrased like this:  she wasn’t brave, she was just lucky.

 Anyone who has spent any time around young people with a terminal condition will know that although many things may be in short supply in those final months, new  treatments for example, that courage is not one of them.  So can I suggest that we ditch the gung-ho language, stop calling sick kids ‘warriors’ and accept that cancer exists not so much on a battlefield but in an enormous  genetic casino. And that it is the job of you and me to work to even up the odds.

Thank you to Jean Claude Dupont who passed on to me this learned and lengthy article about the language used to describe cancer in the popular press.

Thanks also to Maggie Wilcox for the link to this page on metaphor, which took me to this poem.

The Madison Handshake

Thank you to those who put money and messages on Bethan’s Just Giving page for the Cambridge half marathon, which took place last Sunday. The target Cancer Research UK had set me of £300 was dispensed long ago and the total currently stands at nearly £1,500. All of this will go to CRUK’s new Kids and Teens fund.

The messages, though, of course, are more important than the money. I had wanted to create a place where Bethan’s friends and family could come together for her 21^st birthday and to a certain extent this has provided that opportunity.

I am logging a report on the event in the form of poetry. I am not sure if this is what usually happens on Blogspot, but as it’s my blog, I suppose I can do what I like. 

A technical note: the Madison handshake or hand-sling is a cycling term for a relay rider handing over to the next team member by swinging them forward. 

Rites of Passage

At gun time, the column moves off,  

the filter of the canopy on Midsummer Green

shattering the sun into a cascade of snapshots,

rendering our progress in stop-motion capture,

holding this birthday in memory’s aperture.

Panning out of the trees and onto the streets,

I jog in rhythm to the isotonic slosh

of my day-glo flask,

to the drumsticks making the bash barrier crash,

to the vuvuzelas,

to the slap of soles,

to the metres and the feet,

to the rasp and wheeze,

to the sweat and the tears,

to the twenty one years.

A river of lycra

snakes along the high street

between Superdry and Sports Direct.

Heads bob like waves,

their crops lit with haloes of the first sun of Spring,

as though a heavenly host

were entering this celestial city.

College porters,

like dark angels in black bowler hats,

eye me with suspicion

and prepare to eject 
such a sorry wretch
from this procession of the righteous.

A hairpin bend on Silver Street

defies the laws of Physics

as the runners of the future

pass the joggers of the past

both moving in opposite directions.

And in that intersection of time and space

I sense what it is I have come here to find.

Not what I wanted - for that is dead and buried

but what is left.

And though he is not even here,

not even in the county,

I reach across the hairpin

over the miles and the years

and send the Madison hand-sling

to my stripling son,

pass the momentum

from the old to the young

and watch him fly

over the tarmac and onto the home strait,

now beyond the reach of that racing demon
that would have run us down.

Slowing now to a pilgrim’s pace,

I am drawn to the finish in the mighty wake 
of  this Spring tide surge

as it laps over Midsummer Common

and douses Jesus Green in a sea of shining crowns.

Base camp

A cold snap in the November of 2011 and poor plumbing in a Canary Wharf hotel conspired to make a frosty affair of the first of a series of European meetings on drugs development for children with cancer. The suspicion that characterised this first attempt to bring together doctors, drug companies, regulators and families of patients thawed somewhat at a warmer venue in Paris in 2013, which was an altogether more collaborative affair. But if Paris was about cooperation, the meeting in Vienna last week of the newly-named Cancer Drugs Development Forum was, if anything, about the need for action.

The message from more or less all of the parents’ representatives was that if changes were needed to the EU PaediatricMedicines Regulation, then now was the time to get started on pushing them through. This view came from other sides of the table too. Christina Bucci of the drug company, Novartis, argued that we could not wait another year for reform, while clinician, Peter Adamson, of the US Children’s Oncology Group put it succinctly, in what was to become a mantra for the meeting: waiting is not an option.

In the closing session of the gathering, it was therefore agreed to set up an action group to frame necessary reforms to the PMR, based on conclusions that had been reached in both Paris and Vienna.  The group will have its work cut out, though, as it has become clear that this is not simply a matter of narrowing the opportunities drug companies currently have to waive their obligations under the Regulation to develop Paediatric Investigation Plans (PIPs).

As Pam Kearns of the Birmingham Clinical Trials Unit pointed out, the unnecessary red tape associated with the Regulation can not only act as a disincentive to research for children but for adults also. Comparable drugs are often developed by different companies and separate PIPs for each, perhaps competing for recruits from a tiny patient population, make no sense for business, researchers or patients.  Paediatric plans also need to begin earlier in the development process, avoiding the delays companies may make until they are sure an adult product will go to market. Moreover, there needs to be a more flexible definition of what a PIP is. If an adult illness such as melanoma also affects a small number of adolescents then lowering the age of entry makes more sense than creating an additional and unviable trial.

These are just a few examples of how the Regulation could be made more ‘intelligent.’ Sensible amendments like these, however, need to be placed in a wider context. The Regulation does not only relate to cancer, after all, and any changes would need to take into account the knock-on effect with other childhood illnesses. Beyond this, how would a reformed PMR relate to other legislation, such as that for ‘orphan drugs,’ or indeed to the new initiatives discussed in Vienna for creating further incentives for pediatric research?

If the work ahead seems daunting, the message of Vienna was that important inroads have now been made. In the world of health, there is much that simply cannot be legislated for, an obvious example being that of willing cooperation between the many different parties involved. Maoxia Zheng of Genentech / Roche set out how this corporation had developed ‘matrix’ studies in which drugs from different companies have been combined to develop potentially more effective therapies. Pam Kearns countered that an independent ‘broker’ was more appropriate for bringing private companies together and outlined how ITCC itself had created such ‘matrices.’ Either which way, what was demonstrated was that partnerships between commercial competitors are possible and, given the complexity of cell biology and the urgent need for progress, of vital importance.

Regulators, too, demonstrated a spirit for innovation. The Paediatric Committee of the European Medicines Agency are reviewing waivers of PIPs made under the current framework, and their report due next month may well revoke some of them.

I may still not have come down to earth from flight BA0707 from Vienna, but I wonder if when the action group makes its push for change, it may be at an open door. 

We hope to report back at the Childhood Cancer International meeting in Malmo in May and hopefully this will be an opportunity for wider parent / patient input. In the meantime, do please make comments at the foot of this blog.

Go tell it on the mountain

Before this site went ‘live,’ I asked a few friends and colleagues to give me feedback on the ‘beta’ version. The response was very generous  (thank you, by the way), though one senior member of the Clinical Studies Group (CSG) did comment that saying young people with cancer get a ‘raw deal’ was something of a negative statement. A fair point. So I suppose I had better explain myself.

Great strides have, of course, been made in the care of children with cancer over the past half century. In the 1960s most children with leukaemia had no hope of survival; now nine out of ten survive the most common form of childhood cancer, acute lymphoblastic leukaemia (1). This progress is, in no small part, due to the work of groups like the Children’s Cancer and Leukaemia CSG. Since 2001, when the group was set up, the number of patients participating in clinical trials and other research studies has increased fivefold.

Survival rates for all childhood cancers now average at about 80%, no small achievement, but even so cancer remains the most common form of non-accidental death in young people throughout Europe. Moreover, as we have entered the 21^st century (2), a kind of plateau has been reached and for many of the more deadly illnesses, there has been no improvement for two or three decades. Brain tumours, neuroblastoma, sarcomas and acute myeloid leukaemia are all examples of illnesses whose disappointing survival rates seem stubbornly intractable (3). Together these form a cluster of rare conditions which make up a significant proportion of the childhood cancer population.

When my daughter, Bethan, was diagnosed with Ewing’s, one of the bone sarcomas, we were told the survival rates were around 70 / 30, which, putting a brave face on it, did not such seem bad odds. However, despite the best the NHS and one of Europe’s leading cancer centres could offer, she fell into the 30% bracket and, three years later, I found myself requesting a review of her case a few months after her death. The review was sensitively handled, but we had to look some hard facts in the face. Nobody knew why she relapsed, nobody expected it and, when it happened, nobody could do anything about it, apart from make her as comfortable as possible for the months she had left. I remember chatting to the Chair after the meeting and asking how this could possibly be in one of the richest countries on earth. She explained that many childhood cancers are too rare to form a viable market for drug company products and we need to get the industry to invest in research and development. ‘But that,’ she said, ‘is a mountain to climb.’

I wish I had 50p for every time I have heard that story since. I was at a training course on cancer biology recently and both the trainer and a trainee from one of the big Pharma companies came up with the same explanation for the lack of research for children. Does this analysis hold water? Well, to give a referenced source, here is what the main network of European Oncologists has to say:

‘Access to innovative therapies developed by pharmaceutical companies has so far been extremely limited for children in Europe, one reason being that paediatric oncology does not represent a large and hence financially attractive area for drug marketing.’ (4)

Indeed the explanation ITCC gives of the progress that was made in the latter half of the 20^th Century is that this was all done without the help of Pharma, thank you very much.

 ‘Cure rates increased from less than 20% in the 1950s to over 75% in the 1990s and this level was achieved without any input from pharmaceutical companies because of limited commercial interest.’ (4)

But, if we are to move up from the plateau the old chemotherapy drugs have hauled us to, then we will need to develop new, smart ‘targeted’ therapies and:

‘more than 90% of anticancer drugs that should be evaluated in children within the next 10 years are expected to come from big pharmaceutical companies or small “start up" companies.’ (4)

Progress can only be achieved through entering the murky world of commerce and reaching some form of settlement whereby big capitalists and small enterprises are harnessed towards social goals. This is something legislators on both sides of the Atlantic have grappled with for decades now.  One such initiative has been the Paediatric Medicines Regulation, a piece of recent European law that so far has not lived up to the great promise it originally appeared to hold. 

A small band of patient advocates will be journeying to Vienna next month to take part in a review of the PMR and to help formulate a plan to make it more effective. Will this make any difference?

Watch this space.