Yesterday, 43 associations of parents’ and patients’ representatives from 20 European countries sent a joint letter to the Health Commissioner in oder to advocate urgent action to improve the implementation and start the amendment process of the Paediatric Medicines Regulation.
You can share this joint letter on your website, Facebook or Twitter because… (so many reasons):
We have 12 translations of the letter available – check if your country’s national language(s) is available below and share the letter! If you wish to translate the letter in your national language, please contact email@example.com.
Now, we need you to join the plea! Share this letter with the #Unite2cure.
Thank you for your support.
SIOPE – the European Society for Paediatric Oncology and the Unite2Cure network of parents of children with cancer welcome the recognition of unmet needs in paediatric oncology in the European Commission’s 10 years Report on the Paediatric Regulation but strongly regret the lack of urgency and concrete proposals on how the Regulation will be amended to improve the cure for children and adolescents with cancer.
Some of the important concerns voiced by the paediatric cancer community and its supporters are acknowledged in the report. These are:
– For cancer drugs at least, the driving force for the pharmaceutical industry remains the drug’s market potential in an adult cancer rather than the needs of childhood cancer;
– Wide-spread use of the Regulation’s ‘deferral’ system, which leads to delays in paediatric drug development, often until their market of an adult cancer indication is secured;
– Shortcomings of the Regulation’s waiver system, giving companies a route to avoid the obligation for paediatric development for a drug even when the way the drug works might be effective in treating certain paediatric cancers.
Crucially, the Commission confirms the possibility of an amendment of the Regulation, which SIOPE and Unite2Cure have been calling for. Nevertheless, we are disappointed by the lack of urgency for change, with more debate planned and no definite proposals expected until the end of 2019.
Cancer remains the leading cause of children’s mortality by disease in Europe with 6,000 young patients dying each year. Lack of access to innovative medicines is a principal problem behind stagnating survival rates and adverse long-term side-effects in survivors.
Introduced in 2007, the Paediatric Regulation intended to meet the therapeutic needs of children through better-evaluated and authorised medicines. However, progress for paediatric cancer has been insufficient, with only two new medicines authorised for cancer affecting children since the Regulation’s entry into force.
Working with multi-stakeholder experts, SIOPE and Unite2Cure identified the weaknesses in the Regulation and ways to improve it. The European Parliament also called for revisiting the regulatory framework and implementation in its Resolution of December 2016.
A targeted revision of the Paediatric Regulation remains a much needed and urgent step to advance more and better cures for children and adolescents with cancer across Europe.
This is all the more urgent since it is clear that children with cancer do not benefit from the Orphan Drug Regulation. By contrast, the RACE for Children Act was recently passed in the United States which requires that new cancer drugs be studied in any paediatric cancers for which the molecular target of the cancer drug is relevant.
In passing the RACE for Children Act in August 2017, the FDA has made the law catch up with the science, which is unfortunately not yet the case for children in Europe.
SIOPE and Unite2Cure remain committed to advancing the necessary changes in cooperation with all stakeholders and call for the set-up of working groups that would work on the improvement of the Regulation.
Every day, every minute matters to patients – the time to take concrete measures for a brighter future for children and adolescents with cancer is now
Link to the European Commission’s 2017 Paediatric Report: https://ec.europa.eu/health/human-use/paediatric-medicines_en
Link to position statement ‘ Paediatric Cancer Medicines –
Urgent need to speed up life-saving innovation’ https://www.siope.eu/wp-content/uploads/2013/06/1.-Paediatric_Reg_Position_paper.pdf
Link to paper ‘Orphan Drug Regulation: A missed opportunity for children and adolescents with cancer’.
Vassal, Gilles et al. European Journal of Cancer , Volume 84 , 149 – 158: https://www.ncbi.nlm.nih.gov/pubmed/28818704
Link to the 6th Accelerate Paediatric Oncology Conference http://www.accelerate-platform.eu/annual-conferences-2/
Unite2Cure (www.unite2cure.org) is a network of parents, parent organisations and patient advocates from across Europe, which is calling for better treatment and better access to treatment for children and young people with cancer.
Unite2Cure works in partnership with Childhood Cancer International (www.childhoodcancerinternational.org) which is the largest patient support organisation for childhood cancer in the world, and represents 181 parent organizations, childhood cancer survivor associations, childhood cancer support groups, and cancer societies, in 90 countries, across 5 continents.
SIOPE, the European Society for Paediatric Oncology (www.siope.eu), is the only pan-European organisation representing all professionals working in the field of childhood cancers in close cooperation with parents, patients and survivors. With more than 1,600 members across 35 European countries, SIOPE is leading the way to ensure the best possible care and outcomes for all children and adolescents with cancer across Europe.
The SIOPE Strategic Plan – endorsed by all partners in the field – aims to a future where no child dies of cancer and survivors live to the fullest. As the ‘European Childhood Cancer Plan’, it is based on seven key objectives and will inspire all future initiatives in this field.
Contact : firstname.lastname@example.org
Most of you know by now: September is paediatric cancer awareness month.
The 2017 edition is very special: our community of parents, patients and caregivers is waiting for the European Commission’s report on the assessment of the Paediatric Medicines Regulation (to be published around the end of October 2017).
What has Unite2Cure been up to these past few moths?
We have been meeting with the Commission and many other EU officials to convey our message that an amendment to this Regulation could be a game changer for kids with cancer, giving them a swifter and safer access to innovative drugs.
Let’s continue our awareness work on this topic: we need to have a clear legal framework to make sure all kids cancers become curable in the 21st century.
Dear followers, keep spreading our messages and supporting our actions
Last week, Unite2Cure participated actively in the ACCELERATE Paediatric Oncology Conference in Brussels. This event is a unique occasion for high-level experts to reflect upon and discuss concrete proposals to accelerate new oncology drug development for children and adolescents.
The conference is part of a unique multi-stakeholder joint initiative, the ACCELERATE multi-stakeholder Platform. Co-organised by CDDF, ITCC and SIOPE, this platform provides a transparent forum enabling patients and parents’ organisations, academic paediatric oncologists and haematologists, pharmaceutical companies and EU regulatory network representatives to collaborate and jointly address specific obstacles to faster and more effective treatments for children and adolescents with cancer, including the needed changes to the Paediatric Medicines Regulation.
Innovative therapies could target several paediatric malignancies and, thus, save many young lives. However today less than 1 in 10 children in relapse with a terminal cancer has access to these types of medicines, and investment in paediatric oncology drug development is insufficient.
Paediatric drug development is currently regulated in Europe via the EU Paediatric Regulation. 2017 is the year of the 10th year report by the European Commission on this Regulation: 10 years of learning, 10 years of success and failure, 10 years of interaction between stakeholders. A huge experience to build upon in order to accelerate innovation for children and adolescents with cancer.
The Accelerate Conference provided us with a valuable opportunity to discuss successes and failures in paediatric development, as well as to discuss the strategies to accelerate new oncology drug development. It was also a chance to share experience, harmonize and strengthen the collaboration between all stakeholders at the international level (Parents, Academia, Regulators, Pharmaceutical Industry). This year was the 5th anniversary of the conference, and a wonderful chocolate cake was served to commemorate the event.
Angela Polanco, one of Unite2Cure’s founding members, described her overall feeling about the conference: “It was an amazing few days spent with colleagues, friends and new friends. There exists so many possibilities for change and the people to make it happen includes you and me. Change can only be made with passion, dedication and consistency and by not being afraid to have a voice, even when the challenge seems so great. We are excited to see the progress made in the upcoming year, for all those children that deserve to live long and happy lives free from cancer.”
Some points that were presented and will remain a priority for Unite2Cure:
The waivers for adult-only diseases are not relevant in oncology and must be amended: what is most important is the mechanism of action of a given drug,
There must be prior discussions to select the most suited drugs in order to match the best available therapies with children suffering from rare or refractory malignancies,
The delays must be reduced in starting paediatric development of potentially life-saving innovative drugs,
The rewards must be more effective and flexible to increase the interest the development of new and specific paediatric medicines,
We must get rid of the 18-year dogma and allow adolescents to participate in adults trials.
Delphine Heenen spoke to the audience about “Raising awareness and the EU political agenda” with a very well thought-out and moving presentation which drove home our message. She will be representing Unite2Cure again today at SIOPe’s ICCD in Brussels.
Here is just a small part of Delphine’s speech “When my son Raphaël was diagnosed with cancer in 2013, the comforting words most people felt obliged to say were really often the same: “I am so sorry but nowadays, treatments are making such progress, it’s going to be OK”. And I thought it was true. The irony is that IT IS NOT TRUE FOR CHILDREN. My son relapsed end 2015 and when I started inquiring more specifically into the best treatment options for his relapse, I was quite shocked to realise that the most recent drug he had received in 2013 dated back from 1988 -25 years! And the treatment for his relapse was not quite more innovative with the most recent drug being from 1998.
Children are treated with old drugs. They are left out of the innovation we read about almost every week in the papers for adult cancers.
I apologise for the comparison but the situation is shocking; hence shock is what I want to convey: cancer cures are not like movies. There should not be an “adult-only” section. Children and cure belong together!
And we can do better.”
Unite2Cure’s immediate goals following the conference are to continue to push for changes to the Paediatric Medicines Regulation in line with the Resolution adopted by the EU Parliament in December 2016. We will also begin working on the 18 age limit dogma – as there are no medical, legal or ethical reasons for adolescents not to be included in adult trials.
Together, we can make a difference!
February 15th was International Childhood Cancer Day and one way we chose to celebrate was by dispatching our reply to the European Commission’s Consultation on the Paediatric Regulation on the same date as the ICCD call to action. This was the climax of weeks’ of work, cooperating with patient advocacy groups in Spain, Italy, France, Britain, Switzerland and across Europe to push home a set of common messages about the need for better research for children with cancer. You can read a copy of the U2C reply here.
Also on February 15, a feature was broadcast on French TV which showed how cancer affected one Belgian family. Featuring U2C activist, Delphine Heenen, and set up with the assistance of Anne Goeres, this demonstrates why there is a need for ‘more support for childhood cancer research, cure and care.’ You can watch the film at the link here.
The soundtrack is in French or German, so if you do not speak either of these languages, you will have to ask a friend who does. If you do not have such a friend, then make one.That is what this project is all about. 😉
Unite2Cure, Cancer Research UK, and the European Society for Paediatric Oncology (SIOPE) – representing the united voice of parents, researchers and health professionals active in childhood cancer – welcome the adoption of this resolution seeking to improve the current EU Regulation on Paediatric Medicines.
The European Parliament adopted the Resolution during its plenary session in Strasbourg. A key aim of the Resolution is to limit pharmaceutical companies’ scope to avoid the obligation the existing law imposes on them to investigate and develop drugs for children.
Today, companies can ask for a waiver from the obligation to investigate the potential benefit of a drug in a child if the adult cancer for which the drug was originally developed does not exist in children. However, such drugs can still be used to treat other childhood cancer types. For example, – a new drug for adult lung cancer can benefit children with neuroblastoma.
The Parliament Resolution proposes that the existing Regulation is revised by the European Commission to reflect this important distinction, ensuring that the Regulation goes as far as it can for children with cancer in the UK and across Europe.
The Resolution was tabled by Members from across a range of political groups in the European Parliament. It calls on the European Commission to modernise the current legislation to better address the needs of children and adolescents with a life-threating disease, facilitating a more rapid and better prioritised development of innovative therapies for children including for childhood cancer.
Cancer is the leading cause for death by disease among children, with 6000 young people dying of cancer every year in Europe. It is vital that European legislation allows for a more enabling environment when it comes to the research and development of new cancer drugs and medicines for children.
“We, parents and patient advocates want our children to have a chance at a long and healthy life. We will not give up on this. But the problem is that there is still not enough research, not enough drugs and not enough options. At Unite2Cure, we are calling for very specific changes to the Paediatric Regulation to develop more drugs and save our children” commented Patricia Blanc, Anne Goeres, Nicole Scobie, Chris Copland and Delphine Heenen – just some of the many parents and patient advocates at Unite2Cure.
Professor Pamela Kearns, clinical adviser for Cancer Research UK and SIOPE Board member said: “The adoption of this Resolution, advocating important changes to the current regulation, is essential to support a regulatory environment that safely enables and promotes the development of new cancer drugs for children. We urgently need more studies into new cancer treatments for children to improve the lives of children and adolescents diagnosed with the disease.”
Professor Gilles Vassal, SIOPE Past President and Board member said: “The need to accelerate the development of safe and effective innovative anticancer therapies for children and adolescents as well as the need for more studies to obtain paediatric information for paediatric medicines is today a matter of consensus supported by the pan-European paediatric haemato-oncology community and at the global level”
We call on the European Commission to revise the 2007 Regulation on Paediatric Medicines and introduce measures facilitating the testing and developing of new drugs that could potentially be beneficial for children and young people.
AWARENESS RAISING CAMPAIGN:
Social Media Campaign “Let’s Do #More4KidsCancer”
https://www.thunderclap.it/projects/51040-let-s-do-more4kidscancer @SIOPEurope @CR_UK @Unite2Cure #More4KidsCancer
The European Society for Paediatric Oncology represents more than 1,600 professional members across 34 European countries. SIOPE is the leading organisation in Europe fighting to ensure a brighter future to children and young people with cancer, by increasing their cure rate and the quality of their lives on the long-term. Learn more: www.siope.eu.
About CR UK
Unite2Cure (www.unite2cure.org) is a network of parents, parent organisations and patient advocates from across Europe, which is calling for better treatment and better access to treatment for children and young people with cancer. This network is supported by many doctors, paediatric oncologists and researchers from all over Europe.
 G. Vassal, M. Schrappe, R. Ladenstein et al., The SIOPE strategic plan: A European cancer plan for children and adolescents, Journal of Cancer Policy, Volume 8, pp 17–32, March 2016, http://dx.doi.org/10.1016/j.jcpo.2016.03.007
We have just received news that, within days, Members of the European Parliament will vote on a resolution vital for the future of children with cancer. We are asking you to contact your MEPs now, urging them to support the Resolution on the Regulation on Paediatric Medicines on December 15.
Our Toolkit here provides a simple ‘two- click’ procedure that will get a message to your elected representatives fast. It also gives plenty of background on what the Resolution is about.
This is a once in a decade opportunity to transform research into childhood cancers and other young people’s illnesses. Please call on your MEP to represent you and all those that have been affected by cancer by voting YES to the Resolution on December 15.
Thank you from all at Unite2Cure
SIOPE, CRUK and Unite2Cure are calling for EU institutions and civil society to speed up the development of safe and effective anticancer therapies for children and adolescents, as the European Parliament is voting on a Resolution about the EU Paediatric (Medicines) Regulation.
In Europe, less than 1 in 10 children with a terminal cancer have access to potentially life-saving innovative medicines. Ten years after its approval, the EU Regulation did foster progress in paediatric drug development but remained insufficient for paediatric oncology. Too few drugs targeting childhood cancers are currently under development, despite cancer remaining the first cause of children’s death by disease in Europe.
For our campaign, we are using the “Thunderclap” tool: it allows people to pledge a Tweet/Facebook message with our important message, and unleash them all at the same time on 15th December, thereby “flooding” the web. Think of it as a “Twitter flash mob”.
If you are active on social media, we would like to ask you to add your support via Twitter or Facebook, by using #More4KidsCancer, or even posting something gold/a golden ribbon to show that you understand the fundamental importance to increase cure and quality of treatment for children with cancer.
With your contribution, our voice will be stronger!
Thank you very much,
SIOPE, CR UK and Unite2Cure
Professor Pam Kearns talks frankly about clinical trials and children’s cancer.
If you search on Facebook, you can find a picture of Pam Kearns with ‘the girl whose life she helped save.’ In the photograph, doctor and patient share a relaxed smile and an obvious affinity. Pam was Paige’s clinician after the 11 year-old fell ill with Wilm’s Tumour, a rare form of kidney cancer. However, the role she plays in helping children like Paige is not just that of providing treatment. She is Director of Cancer Research UK’s Clinical Trials Unit and a leading figure in the search for new ways to combat paediatric illnesses like Wilm’s.
Paige’s story is a heartening one but if you go to hear Pam speak, she will show you another side of the picture, flashing up on a Powerpoint slide the words of different child’s father:
‘It is inconceivable in this day and age that, globally, there is no drug that can cure my daughter’
Any child diagnosed with cancer faces an uncertain future and to find out more about why this is so and what can be done about it, I went to visit Pam at the Clinical Trials Unit in Birmingham on a sweltering morning this June.
Pam and I have known each other for 5 years through involvement in various projects to do with childhood cancer, but I had never visited her on her ‘home turf’ and I was curious to know how the ‘nerve centre’ of childhood cancer research in Britain operates.
She welcomed me into a surprisingly modest office she shares with a sleek, carbon-frame Cannondale, the bike she uses for a 20 mile daily commute and the sportive challenge she promises she will get round to soon.
I start at the beginning and ask her what exactly the Clinical Trials Unit does.
‘Lots of people don’t know what a Trials Unit is and that includes many clinicians. There are about 30 Trials Units within universities in the UK, of which about a dozen or so are dedicated to cancer and 8 are core-funded by Cancer Research UK.
‘The aim of a Trials Unit is to be the place where an investigator comes with an idea about improving treatment, whether it’s giving radiotherapy in a different way, introducing a new drug, a new type of surgery, any clinical idea that changes the patient pathway. We work with them to see if it’s a viable idea and if it is, we help design the trial, collect the data – everything from concept to completion; the only thing we don’t do is recruit the patients.’
Who pays the piper?
I ask her who funds the research.
‘By far, the majority of paediatric cancer trials are charity funded. Cancer Research UK (CRUK) is our biggest funder; they fund the core team (at the Clinical Trials Unit) and if a trial is good enough, they’ll fund the trial too. We sometimes manage to get into collaborative partnerships with the pharmaceutical industry where they will give us a grant and a drug to support the trial.’
She gives the example of a major investigation into leukaemia.
‘ If you look at the AML trial which we’ve just launched, that has a lot of questions about how to use standard chemotherapy, but it’s also got a drug called mylotarg, which industry are still trying to get a licence for. The majority of the funding is from CRUK but there’s also a large grant from Pfizer – plus the drug. So that’s a true partnership, where you’ve got charitable funding delivering the academic questions plus Pharma contributing to answers we are interested in – important to patients, to families, but because they are also interesting to Pharma, they are investing money in it.’
She goes on to explain, though, that ‘we don’t necessarily need the industry’s involvement if, for example, we’re asking questions that are about generic drugs.’
When she refers to generic drugs, she means ones that are already commercially available. She explains that in past decades, many of the advances in children’s cancers were made by simply repurposing generic drugs originally licensed for use with adults. Even in the present day, a lot of research simply involves revisiting generics already well-established with children, refining their doses and tweaking their combinations. This process, however, she argues, has run its course.
Big Pharma and Small Biotechs
‘We’ve hit a plateau of improvement in many diseases,’ she explains. ‘To make the step changes we need in the future, I don’t think we are going to achieve that by just using generic drugs. We need new approaches, new drugs with different mechanisms of action that we can add to our armoury. That’s when we need the industry to give us access to their new drugs and innovations.’
The revolution in genetic science in recent years has stimulated a new wave of commercial drug development. These are the so-called novel agents that target illness at a molecular level and which hold great potential for shifting children’s cancers off the ‘plateau.’
A drug is usually licensed to treat a specific type of disease or cancer. If doctors feel that a particular drug may help a patient with a condition not included in the drug license they can prescribe that drug for the patient. But the doctor has to take full responsibility for the outcome. This is called ‘off label prescribing’. Many clinical trials for cancer use medicines ‘off label’ in this way. The trials want to find out whether drugs licensed for a particular type of cancer could help to treat other types of cancer.
The problem is that the pharmaceutical industry is adult-orientated. Its focus is on the blockbuster markets created by the common cancers that afflict older people, rather than on the messy patchwork of rare conditions that are children’s cancers. Pam’s concern is with the delays involved in waiting for new agents to be commercially developed for adults before we investigate their potential in children.
‘If there was a generic drug, a drug that had come off its licence now,’ she explains, ‘ and that was being used for adult cancer and we wanted to use it in children because we had scientific evidence that it could make a difference, we could go ahead and do that.
‘But what we’re saying is, “Look, drug companies with your massive pipelines of new drugs, you’re developing targeted drugs that would be useful to children now not when that drug has been developed for adult illnesses.”
‘It’s about acceleration. We could wait until X or whatever targeted drug has been licensed for adults and then repurpose it for children and just carry on the way we have before. But we’re delaying access to children by sometimes 30 years. So the whole purpose of this is getting into the drugs pipeline really early, before the drugs are on licence in adults and let’s see if they’re interesting in children.’
I ask her why we are so dependent on the private sector. Could not research centres in universities or hospitals simply develop the drugs themselves? The answer, of course, is about money.
‘It costs a huge amount of money and there’s high attrition rate [ in drug development] and academic departments would struggle to do that. I’m not saying they don’t exist. There are drug discovery units, for example at the Royal Marsden’s Institute for Cancer Research but they can’t turn on the high throughput screening in the way industry does. If an academic department developed a drug, there is no reason why we would not work with them, but at some point they will hand on the further clinical development to a small biotech and if it’s good, it will be bought up by Pharma. It’s the money that’s required to develop the drug.’
She gives an example from Birmingham.
‘My colleague, Frank Mussai, he’s doing some really interesting work looking at a particular pathway relevant to childhood cancers, and he’s found a biotech company based in Asia who produce the drug that targets this pathway. They’re not rich and they haven’t got the expertise to do the clinical trials, so they’ve been giving him small amounts of money to do his lab research. They’ve been giving him access to the drug to develop the laboratory research. Today we have finalised a grant application to the charity sector to do a trial in paediatric cancers .
‘Now if that drug were ever to become a blockbuster, then we would get some of that investment back so that we could develop the next set drugs. But that would be a rare event.’
From Brussels to Birmingham
The conversation inevitably shifts to the measure the European Union introduced to stimulate commercial interest in children’s drug development, the Paediatric Medicines Regulation. Both Pam and I are involved in campaigning to reform the Regulation and are aware of its disappointing record to date. However, she emphasises that it has had an effect.
‘I can remember the days, ‘she says, ‘of going to big cancer conferences and talking to a Pharma company at a stand about drug that was relevant to my research and they were really interested in talking to me as a medic until I said I was a paediatrician and they were like, “How quickly can I get this woman away from me?”
‘And that attitude has changed and it’s changed because of the Paediatric Regulation. There is a benefit; it might not have translated into new drugs for children but a positive attitude change has happened. ‘
I ask her about a similar campaign she was involved with, around another piece of Brussels legislation, the Clinical Trials Regulation.
‘It feels like it was a huge chunk of my life,’ she sighs. ‘But it was only two years’ serious campaigning ’
The important point, though, was that the campaign was broadly successful and layers of unnecessary bureaucracy that hold trials back are scheduled to be peeled away.
What did you learn, I ask her, from the experience of that campaign?
‘That you had to work with the European Parliament and the relevant rapporteur,’ she says. ‘But rather late in the game we realised if you don’t have the European Council on board, the changes you want could be voted out. I think we were quite late in engaging with the member states. For the UK, we were in a better position because the MHRA (Medicines & Healthcare Products Regulatory Agency) were taking the role on behalf of the Health Minister and they were sympathetic to the changes we wanted, so we were pushing at an open door. But that wasn’t the case across Europe. We met with health attaches from one of the member states and they were still concerned with clinical research in children being unethical. So they were miles away from where we wanted them to be and they were the people sitting around the table at the vote.
‘This is what we need to remember with the Paediatric Medicines Regulation. We know the arguments inside out but when you sit down with someone for the first time, they’ve only got this vague idea what you’re talking about so getting that sound bite, that message across is really important.
That’s what I learnt.’
Ethics and Equipoise
I pick up on the worries about the ethics of involving children in research and ask her to explain about randomised trials.
|Phase 1, 2 and 3 – What’s the difference?
Clinical trials are often divided into three stages or phases. Earlier phase 1 trials focus on how much of the drug it is safe to give and whether it actually shrinks the cancer. If a phase 1 is successful, the therapy will be tested more extensively in phase 2 and 3 trials. A new treatment usually needs to go through phase 3 before it is accepted as standard.
Phase 2 and 3 trials are often randomised. This means that people taking part in the trials are divided into different groups at random, with each group being given a different treatment or arm. Trials that compare three or more treatments are called multi-arm trials.
‘When you are doing a randomised trial, there should be no prior knowledge or belief that one arm is better than another. This is what we call equipoise. As a clinician, when I sit down with a family and I ask a child to participate, I can explain the background to both the arms but I should be able to say, hand on heart, I don’t know which one is better. If I did know, it would be unethical to ask someone to take part. ‘
She refers to the major randomised trial into Ewing’s Sarcoma, the illness my own daughter had.
‘It is like Euro Ewing’s 2012. Do you want to participate in a comparison of the known gold standard in Europe against the known gold standard in America? We cannot differentiate between the two and now we are asking the question which is more effective and which has fewer side effects.
‘Equipoise is about randomised trials. However, there is no equipoise at phase 1.
‘In a phase 1 trial, the ethical question is that you are asking a parent for their son or daughter to participate in a trial that may not have benefit for their child.
‘Now you can ask an adult to take part in a phase 1 and it’s that adult’s informed decision on the basis of altruism and, undoubtedly, a little bit of hope that they’re going to get the “miracle response.”
‘The Declaration of Helsinki states, however, that you cannot do clinical research in children when there is not at least the potential for benefit, which means you cannot do the type of ‘first in man’ studies you can in adults, starting from very low doses. There needs to be evidence from laboratory research or clinical trials in adults that suggests the treatment could have a benefit at the doses given to a child.
Talking to families
I ask her how she puts the option of a phase 1 trial to parents and child.
‘If I can give this in very personal terms , when I sit down with a family to talk about a phase 1 study, particularly a family I have never met before, the first thing I do is establish their understanding of where a child is in (I hate the expression ) the “cancer journey.”
‘So do they understand their child has no curative option? And that it’s effectively palliative at that stage? Because, without that understanding, the rest of the discussion about the phase I trial is almost dishonest. The eligibility criteria for most phase 1 studies is that there is no known better curative option. I then explain to them the background to the trial but I also say what the other options are and those might be purely supportive.
‘It might involve using a drug like etoposide. We don’t have a lot of published data to prove this has benefit but substantial clinical experience tells us that it has some success in holding back the progression of disease in some children.
‘I’ll explain where the trial is in terms of the drugs development, what the implications are of being in that particular trial. Does that mean more time in hospital, more blood tests, more investigations, backwards and forwards from half way across the country to visit me?
‘I outline all that.
‘I strongly dissuade families from going, “Where do sign?” ‘I always say, “Go away and think about it, talk about it.” And I talk to the child about it, depending on their age.
‘Morally, ethically and within the Declaration of Helsinki, you never ask a child to participate in a trial where there is no evidence of benefit. But the chance of the benefit has to be understood to be quite small and then it comes down to the motivation of the family and the child and whether they want, at least, to try something.
‘Now my experience is that each family is different. You get some families that respond saying, “I don’t really want to have anything more to do with hospitals – that means we can have some life together for a while.” They’ll do that. They won’t participate in phase 1 clinical trials – and that’s fine.
‘Then you get the different kind of family that says, “Whatever there is. They want to know if a phase 1 trial fails, what’s the one after that and what’s the one after that. They want to keep going. They want to be involved in something that brings their child to the hospital and might have the potential for a miraculous benefit.
‘There’s another kind of family. Often it’s done with the involvement of the child in the decision making; for example, slightly older children. They really know there isn’t much chance of benefit but they feel they want to be doing something, even if it is for someone else. That’s extraordinary, in my mind, but parents have said to me that at least we tried to do something even if that something is for somebody else.
‘I am forever in awe of all three sets of families. None of them is making a right or wrong decision. My job as a medic is to listen and answer questions and hope they go away feeling they have made the right decision for them and their child.
‘It’s a hard area and that’s why it shouldn’t be done in every centre in the country. It must be done by people who have that experience of talking to families about these issues.
‘Most of our experience is in breaking bad news to parents, because the majority of children treated are very young. It is harder to gain the experience of breaking this type of bad news to the age group of children who are just starting to be old enough to understand.
I remember doing it for the first time when I was a junior doctor and I can remember, to this day, this teenager whose disease had become incurable quizzing me really hard about what was going to happen and I wanted to run away from the question’
‘It would have been really easy to say, “It’ll be fine” and patronise this teenager. But I stuck in there and that is something we all need to do.
In passing, I mention the difficult exchanges we had with our consultant over the only trial my daughter was offered in the whole period of her relapse. I relate the mobile call just before Christmas in which we turned down a phase 1 study of aurora kinase, a drug I have heard nothing of since in relation to Ewing’s.
‘That’s because the clinical development was abandoned,’ says Pam, ‘because it didn’t work. They completed the study but it wasn’t effective in anybody.’
We talk about the children who are never offered the option of a trial – because the trials are full, because the children do not meet the eligibility criteria or, as is more often the case, because the trials are simply not running.
I ask her about compassionate use, which allows patients access to new medicines, even hough they are not enrolled on a trial.
‘Compassionate use exists in America. We’ve got it here too. It’s called “Named Patient Access.”
‘As an example, it is possible for a child with leukaemia to get access to inotuzamab, even though there’s no trial open for that drug at the moment. We could open the trial of this drug when we get through all the regulatory paperwork. Compassionate use of drugs cannot substitute for proper drug development because we’ll never know if we just use it compassionately whether the drug should be properly developed and marketed and available to everybody.
I push her on whether we can get more children off phase 1 and onto phase 2 studies, where the emphasis is less on the safety of the drug and more on its efficacy. She talks about a new trial.
‘That’s the aim of E-smart. It will have multi-arms and, as new drugs become available and they’ve got their safety data, we can slot them into the trial. When the child has that molecular pathway identified, it doesn’t matter whether it’s Rhabdomyosarcoma or Ewing’s, does it have the target for that drug, can they enter the trial? And we’ll just keep that trial open and growing as long as we can get access to the drugs and that’s the sort of trial we need more of.’
The chances of surviving a childhood cancer have changed very little over the past two decades. Sophie Fessl talked to parents, doctors, regulators and researchers about what has to be done to address this disastrous impasse. “It feels odd to say this, but Elliot is one of the lucky ones.” The comment comes from Nicole Scobie (photo, above, with Elliot), and refers to her son, who was only four years old when he was diagnosed with a stage IV Wilm’s tumour. His left kidney was engulfed by a huge cancerous mass and his lungs were full of metastases. The heart-stopping diagnosis was just the start of a rollercoaster of emotions, hospital stays and exhaustion. But this is a story with hope: Elliot responded well to chemotherapy. He went into remission after 10 months of treatment, and has remained so for the past four years.
“At least for his cancer, there is a treatment that works,” says Nicole. Not all the children she and her son befriended during their long stay at the Lausanne University Hospital’s children’s cancer ward can consider themselves as ‘lucky’. Elliot became close friends with Zoe, a little girl battling an aggressive neuroblastoma. But while Elliot’s prospects looked good, for Zoe, the odds were stacked against her. In the end, there was nothing her medical team could do: Zoe died in her mother’s arms aged four.
The difference between Elliot and Zoe? Elliot had a type of cancer that has been successfully treated for decades, being one of the first childhood cancers – alongside acute lymphoblastic leukaemia – to benefit from the chemotherapies pioneered by Sydney Farber back in the 1950s. His is part of the celebrated success story that saw cancer survival rates among children increase from 10% to 80% over 50 years.
Zoe, by contrast, had a type of childhood cancer that remains fatal in the majority of cases. Her story is shared by 6,000 children and young people under 24 who are still dying of cancer each year in Europe. For parents like Nicole Scobie, who’ve seen their child’s life in the balance, that is a heartbreaking statistic. But there’s a worse one – the mortality rate from childhood cancers has barely changed over the past 16 years.
Last year, Scobie was one of a large group of parents and advocacy organisations that got together to found Unite2Cure, an advocacy organisation that aims to kickstart progress again.