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Expert network works towards better drug development for children

IMI project c4c has pioneered an advice process involving diverse experts including patients to aid drug developers when designing paediatric clinical trials.

09 February 2023
A child places their left hand on the upturned palm of a man's right hand. Image by Juan Pablo Serrano Arenas via Pexels.
In c4c's advice process, experts can include patients and their parents. Image by Juan Pablo Serrano Arenas via Pexels.

Up until relatively recently, children were treated like “little adults” when they were sick . Medicines specifically made for children were almost unheard of, and instead children were prescribed medication at lower doses, accounting for their weight.

“Originally it was thought that your child is just a small adult, and then [clinicians would] linearly correct for weight [to give them the right dosage],” says Prof. Saskia de Wildt of Radboud University Medical Centre.

However, this doesn’t always work. Clinicians quickly learned – because sadly, children died – that newborns and young infants often require even less of a medicine than their weight would suggest, because their organs are immature. And for toddlers, it’s the reverse –  their rapid metabolism means that toddlers may need a higher dose than you would otherwise expect, compared to an adult.

“Kids also may respond differently to drugs,” says Prof. de Wildt. “So even though you give the right dose, they still may respond differently. That’s one of the reasons that all of this research was started.”

In 2007, the EU Paediatric Regulation was passed, which required appropriate testing of paediatric medicines through clinical trials in children. But developing drugs for children comes with its own suite of unique problems. A one-year-old might respond differently to a seven-year-old, so the pharmaceutical industry needs to run tests on a wide variety of age groups. Children are also constantly growing and their physiology changes rapidly in just a short number of years, so tests must be performed quickly.

“It's very difficult to recruit patients, and there has been a lack of infrastructure across Europe to facilitate the conduct of studies in children,” says Dr Katharine Cheng, Senior Director of Paediatric Drug Development at Johnson & Johnson.

Added to that, children’s illnesses are often classified as rare – which means that clinical trials may be even more difficult to conduct as the number of potential patients is so small.

The Innovative Medicines Initiative project conect4children (c4c) sought to tackle this problem by setting up a Europe-wide network to make clinical trials in children easier to conduct whilst also connecting clinicians, academia, methodology experts and parents to ensure high-quality clinical trials for children’s drugs.

A pilot expert advice process was developed under c4c, through which drug developers can easily access a wide array of important information directly from experts when designing clinical trials. The idea is that drug developers can come to c4c asking for advice in relation to the treatment of a particular childhood disease that they are targeting. An advice group is quickly formed which the drug development company can then consult. The “experts” included not only clinicians, researchers and methodology experts, but also parents and patients themselves. The network is described in a recent paper in the journal Clinical and Translational Science.

“For example, if the experts can propose a [clinical trial] design that might be innovative, maybe reducing the sample size or reducing the need for a large trial, that can make the paediatric drug development more feasible,” says Dr Cheng, who was the joint lead author on the paper outlining the pilot.

“And if an advice request was around a study design, the patient or parent perspective might say well this is unacceptable, I can't take my child out of school once a week to come for a clinical trial visit. Or they might say there's too many blood tests here.”

“Even on outcome measures, a clinician might find a specific blood value important whereas a patient might say well, I have a terrible headache every day so for me it's more important that my headaches are gone than that my blood value changes,” says Fenna Mahler of Radboud University, joint lead author on the paper.

Twenty-four expert groups comprising more than 400 experts were set up as part of the advice process. The first advice request was made in the second half of 2019, and as of 30 September 2022, 36 advice requests had been received. The c4c network also developed a standardised contractual system for the c4c industry partners and the experts, which greatly reduced the administrative burden for drug development companies.

“It's unique that we have all these different types of expertise throughout different countries in Europe, all paediatric expertise that you can get via one single point of contact,” says Mahler. “We have also diminished a lot of bureaucracy and legal hassle, which always takes time for the sponsor as well as the participating experts.”

The c4c network is now working to turn the pilot into a sustainable fee-for-service endeavour, which companies throughout Europe and beyond can benefit from.

c4c is supported by the Innovative Medicines Initiative, a partnership between the European Union and the European pharmaceutical industry.