Clinical trials provide the unbiased evidence essential for improving treatments in all areas of medicine. For children with cancer the development of safe treatments that work has relied on high quality clinical trials. In the UK, we have a clinical trial available for over two thirds of children diagnosed with cancer. And they have contributed to over 80% of children now surviving cancer diagnosis for five years or more.
The vast majority of clinical trials for childhood cancer are designed by highly experienced paediatric oncologists and are conducted in collaboration with academic organisations and funded by charities and public money.
These trials aim to improve the best clinical treatment for children by optimising the current standard of chemotherapy drugs. For example, the current clinical trial for children with acute lymphoblastic leukaemia is investigating if controlled and limited changes to the standard treatment can reduce both side effects and increase the cure rate for this disease.
The majority of trials for children with cancer don’t involve any new drugs; few new drugs have been developed to treat children’s cancers over the last 30 years.
Going off label
And most drugs currently used to treat childhood cancer were not developed by the pharmaceutical industry for this purpose - they were developed for the treatment of cancers that affect adults and their current use in children is termed “off-label” (not used for the disease for which the drug is licensed). This type of use is safe, but only because it is based on decades of academic clinical trials run by universities and hospitals, collecting information on the safety and effectiveness of these drugs.
In 2007, the EU Paediatric Regulation was introduced to promote research into medicines for children and it has motivated the pharmaceutical industry to invest in drug development programmes for childhood diseases. But the greatest advances in treatments of these children will continue to be through clinical trials that carefully test step-wise improvements in current medicines, including their off-label use.
This progress was severely inhibited by the EU Clinical Trial Directive (EU CTD), which has governed clinical trials and which also became one of the most heavily criticised European laws. It resulted in a major decline in clinical research because it didn’t recognise differences in types of clinical trials and added a huge burden of costs and paperwork.
But now the laws that regulate clinical trials in Europe are about to undergo a crucial and welcome change. The new Clinical Trial Regulation promises to bring pragmatic changes to the law that will significantly reduce the excessive level of administrative and financial burden for this type of clinical trial while still protecting the rights and safety of patients.
What is ‘low risk’?
The new regulation proposes to introduce the concept of a “low risk trial” category for clinical trials - ones that aren’t deemed to present many (if any) dangerous side effects. Trials designated as “low risk’” will be subject to a fair level of regulation, reserving appropriately high levels of governance for trials that pose a more substantial risk to patients; for example, completely new drug trials. This does not mean that patients in low risk trials will be unprotected but it does mean that the control will be focused on trials that are very different from normal clinical practice.
This is good news for childhood cancer trials but the devil is definitely in the detail. The precise definition of what constitutes a low risk trial is currently being heavily debated in the European Parliament and there is a risk that the proposed wording will exclude almost every cancer trial that involves a chemotherapy because there are very few examples that are not associated with side effects.
However, these side effects are also seen in normal clinical practice. Chemotherapy side effects need to be seen in the context of the life threatening nature of the disease being treated. The crucial factor of whether a trial should be considered as low risk is if the level of additional risk is low compared not participating in the trial altogether.
The success of this new law in introducing fair regulation will pivot on getting this definition right. It must fully recognise the needs of children with cancer and all rare diseases where clinical research is being impeded by unnecessary bureaucracy at the expense of developing potentially life-saving new treatments. Ultimately it will not be possible to continue to conduct academically-driven clinical trials that provide the evidence that underpins the best clinical practice for children and young people with cancer.