The European Society for Paediatric Oncology (SIOPE) is calling for the age of entry to clinical trials to be reduced to 12 years in all early phase studies (where medically justified) to enable children/adolescents with cancer to have better access to medicines.
Survival for many adults with cancer has significantly improved in recent years thanks to innovative targeted drugs. Innovative and experimental therapies are curing the more difficult to treat cancers like never before in today’s ‘golden age’ of cancer research. However, such treatments for children/adolescents regrettably still lag far behind. Today, the vast majority of children are still treated with conventional chemotherapy, which may lead to long term health problems due to the late effects of treatments.
Unfortunately, the current reality is that a child or adolescent may not benefit from a potentially life-saving treatment because clinical trials often exclude those aged 18 years and below. The reason for this is not related to safety and science but simply because ‘this is the way things have always been done’. If adult trials were more flexible with their age of entry, this could generate more opportunities for better access to medicines for children and adolescents with cancer.
Breaking out of the status quo in paediatric oncology
So why do we typically do the things that we do? Because it is what we’ve always done, we feel it is the most suitable way of doing something, or it might just be easier. It doesn’t require us to challenge and change anything. Of course, there is nothing wrong with the status quo, as long as it is working, thriving, and flourishing. But the status quo for children/adolescents with cancer is not acceptable.
The reality is that each year across Europe, more than 35,000 children and adolescents are diagnosed with cancer and 6,000 die from their disease. It is said that ‘children are our future’, and so it is surprising to learn how far research into young people’s cancer is far behind that for adults. What can be done to challenge this status quo? There is an urgent need for the cancer research community to make clinical trials more inclusive for both better science and because this could save more lives.
Separating children and adults in clinical trials
It is quite remarkable that oncologists are making breakthroughs in cancer care, but we are unable to get these treatments to children fast enough.
In a study in 2016, Whelan and Fern demonstrated that out of 49 trials of cancers common in teenagers and young adults, only six had age eligibility criteria that corresponded to the biological age range of the diseases. Current clinical trials that are ‘adult-only’ are in fact holding back young people from getting access to new treatments. For example, a new drug for Hodgkins Lymphoma was approved for adults in 2012.
However, a paediatric trial for the same drug and the same disease was still ongoing in 2016. Current practices also lead to ghost trials where there are too few patients recruited to the trial for any useful data to be collected. This occurred with a drug for the treatment of melanoma, which was approved in Europe for adults in 2012. A trial for adolescents with melanoma was opened in 2011 in ten countries and four continents. Four years later, still only six patients had been recruited (Gaspar et al, 2018).
We need to overcome this artificial idea of separating children and adults in clinical trials. We should instead rethink the idea of someone turning 18 and suddenly becoming an adult. This artificiality is failing children and young people with cancer but is also hurting medicine.
FAIR (Fostering Age Inclusive Research) Trials to change the status quo
The FAIR Trials working group was set up to facilitate age inclusive research. The key proposal is for the age of entry to clinical trials to be reduced to 12 years in all early phase studies (where medically justified), with no need of a prior paediatric trial. This may look like an ambitious target, but there is no great obstacle in terms of law, regulation, or safety. The issue is rather one of awareness and generating willingness within the research community. The FAIR Trials working group therefore intends to work towards a culture change through:
- Identifying trials that are truly age inclusive and give visibility to these success stories
- Engaging with ethics committees, national and international research networks and with industry
- Giving media visibility to the topic of FAIR Trials.
There is a growing body of evidence supporting the need for age inclusive research and this fact-based information should reach all stakeholders to enable a culture change. Many assume that children with cancer would be at the front of the queue for newly developed drugs, but sadly the reverse is true. FAIR Trials is trying to change this reality.
Age limits for clinical trials
Together, we should remove the age limits for clinical trials. There is a need for better and stronger partnerships between scientists, clinicians, and pharmaceutical companies, particularly since significant improvements have to be made when trying to identify which drugs should be developed. Going forwards, it is crucial to have a multi-stakeholder collaboration, especially with industry. The science is evolving and, as more knowledge emerges about the fundamental drivers of paediatric oncology, there has to be a willingness and an openness by industry to work together with all those seeking to remove this artificial age barrier and deliver better health care.
Professor Pamela Kearns, SIOP Europe President, said: “EU regulations don’t say that a young person should not be included in trials, but this is just the way boundaries have been set historically. It is my hope that age limits will not be a barrier in the future. We don’t look at the fact that a child is below or above 18 years of age. It is about the way the drug works, the biology of the disease and the needs of the patient. That is where the future of clinical trials needs to be.”
In such a context, it is very important for the European paediatric community to work closely with parent groups and pharma companies to get targeted anti-cancer drugs to children and adolescents as soon as possible. For the children and adolescents suffering now, change can’t come fast enough.
The European Society for Paediatric Oncology (SIOP Europe)
+32 2 880 62 82
Tweet: @SIOPEurope #FAIRtrials