It is now 20 years since I recruited my first paediatric patient to the first randomised clinical trial that I was personally involved in. 

Ironically, I remember many of those events and conversations better than I remember what I did last week, such was the impact that it has had on me: five of the children that took part in that children trial have since sadly passed away, along with many others that lived with that tragic disease, and there is still no treatment available to address the high unmet need of the neuronopathic Gaucher disease community.

Not that there hasn’t been some progress made since that failed clinical trial. We do now have other clinical trials on the horizon and some of those young people have reached adulthood and continue to inspire us. One such individual is Maddie Collins, our Project Coordinator here at Aparito, who recently became the proud mum of a baby boy. 

I have been part of the EFGCP Programme Committee for a while now, and despite my passion for this topic, I have recently struggled to support the organisation of a conference where, more often than not, I felt that we were repeating the same old topics and issues since I first attended the conference back in 2007 when the Paediatric Regulation came into force here in Europe. 

But there were glimmers of hope this year and I’m pleased to say I was far more enthused and energised at the end of the Better Medicines for Children conference than I have been in some time. 

It was great fun to host the fireside chat with Prof Koen Norga the Chair of the Paediatric Committee (PDCO) at the European Medicine and Dr Angeliki Siapkara from the MRHA here in the UK, and a former PDCO member until Brexit enforced her departure. 

As colleagues of old, we had an honest and warm conversation (despite the virtual fireside that is Zoom) and the discussion primarily focused on the value of global collaboration, a topic that was echoed with the global presence of regulators from Japan, China, and Brazil, and moderated by Marie Valentin from the WHO.  

Indeed, it was the regulators’ contribution to the conference that made the show for me this year, with many of their key take-home messages resonating loudly:  

Regulators are not the barriers to innovation 

It is possibly notable that two of the most impressive speakers at the conference were from the Nordic region, representing the Norwegian and The Danish Medicines Agency – Anja Schiel and Frederik Grell Nørgaard.

Over the years, I’ve heard Anja say a few times “this might not fit in our current way of thinking but…”. I have a huge amount of respect for her and she’s enabled initiatives that were otherwise facing roadblocks.

Based on a quick Google search (always a dangerous task!) it seems that the cultural traits for the Danes are for authorities, decisions and orders to be challenged! Not to make sweeping cultural generalisations but it is reported that the Danes are schooled from an early age to ask questions, challenge ideas and debate positions. 

In the breakout session on Decentralised Clinical Trials (DCTs) Frederik Grell Nørgaard presented all the efforts undertaken by the Danish Agency to support the frameworks for DCTs. I loved his reflections that regulators were to be cautious and conservative but not ignorant or stubborn! The regulator’s role in DCT discussion is to ensure that the GCP regulation and rigorous requirements of clinical trials are maintained and that we don’t throw the baby out with the bathwater (ICH GCP is still the framework for DCT). 

He implored the industry partners to show good examples to regulators and to include decentralised elements in paediatric trials now. This is an easy win for us all that can be evaluated iteratively, and something that we’re increasing demand for at Aparito as companies are leveraging the power of remote patient-generated data as part of hybrid studies and the ability to co-develop digital endpoints that convey what’s important to patients. 

Study sponsors must justify why decentralised elements are needed in clinical trials, which are appropriate for the condition and the product and useful to answer the scientific question, but most important an advantage for the patients and for addressing the scientific question (not for saving costs for the companies!). 

The advantage for the patients (and their parents) must remain central to this. One of my personal concerns that I expressed in the DCT breakout session was that we must not allow the pendulum to swing too far, where we convert children’s homes into mini laboratories, damaging the safety comfort net of home. 

We must not move the burden of responsibility (or the dirty work of enforcing compliance to conduct painful tests) onto parents – they have more than enough burden to carry on their shoulders. Our duty is to make the experience easier for them, logistically and emotionally. 

But progress feels painfully slow, and it seems to take an incomprehensible amount of time to make changes – I regularly get frustrated with just how long it takes for some initiatives we’re driving, or are part of, at Aparito to bear fruit. 

And yet, in the development of a vaccine for Covid-19, we can only be amazed and rejuvenated by the rapid progress, including the early consideration and inclusion of children and adolescents to avoid years of off-label prescribing. The benefit of parallel working without shortcuts to quality standards led to rapid timelines that were beneficial to all. 

Anja Schiel was clear – there is not too much innovation, but we risk having too many innovations at the same time. And we must be careful that we’re able to address the risk and uncertainty of each innovative approach both individually and collectively. 

While the agile, ‘fail fast’ approach of the tech world should never be adopted in drug development, I’m a strong advocate that we can embrace an agile framework with pre-defined go-no go rules that keep the safety of the participants and the quality of the data coming through iteratively. 

To make innovation work in drug development, we must take the regulators with us on the journey.

We must justify the approach, be transparent and plan early.

We must convey the journey, including all the bumps in the road to the regulators early and often, so that they can follow the context and understand the rationale. 

After all, we all want to be part of the main storyline – not just passive passengers in someone else’s adventure. 

via Elin Haf Davies/Twitter

The conference finished with concluding personal remarks by Dr Agnes Saint-Raymond as she retires after a lifelong commitment to child health, and what a highlight!

Her no-nonsense direct, to the point messaging, was a great reflection of her style which has uniquely helped her propel the Paediatric Regulation into existence, and now celebrates 350+ approved medicine with paediatric indications and 50 pharmaceutical forms, on the back of 4561 Paediatric Investigational Plans agreed. 

Agnes appointed me to join the Paediatric Team at the European Medicine Agency in 2007 and I remain forever grateful for the six years as a regulator under her drive and guidance. We all need role models like Agnes in our early-mid careers. 

Although advocating for an evolution rather than a revolution (which I was slightly disappointed about!) she implored for us to stop the blah blah blah talking – and move from discussion to action. 

Time to stop talking and start working on definitions of unmet paediatric needs so that the development of paediatric medicine can remain in the “industry’s reality” but make faster and specific progress where it’s most needed. 

She also advocated for relying even more on extrapolation and the integration of modernisation of clinical trials, including the use of AI! A life-long regulator advocating for innovation – a dream statement! 

In 2010 I co-authored a paper with Agnes titled Paediatric investigation plans for pain: painfully slow! which examined the slow progress made since the regulation came into force. Our concluding sentence stated that “Now is an opportune time for clinicians, academics, learned societies and industry to collaborate for the benefit of children in pain”.

Eleven years on – can we say that it’s an opportune time NOW? 

I say YES, it must be so! I refuse to be having the same conversation in another 10 years’ time! Much like Agnes, I’m not known for my patience and with the high calibre of children and young people that also contributed to the conference via pre-recorded videos or in person I am convinced by their eloquent and articulate contribution that they will not patiently wait for another 10 years either. 

“Children are not the people of tomorrow, but people of today.”

Janusz Korczak

Let’s make our actions count today. 

Dr Elin Haf Davies, CEO