Innovation coming to paediatric research

Background and method

Innovations for clinical trials may accelerate bringing new medicines to children, such as through more robustly quantifying treatment effects, combining phases and ages, expanding access, and more often involving patients and their organisations in the design of trials and documenting patient-centric endpoints. The objective of this page is to continually track such innovations using information on clinical trials and to present original insights.

Information from the EU Clinical Trials Register and ClinicalTrials.Gov was used for this analysis . For commenting, the full R code is included below. Paediatric trials were identified based on the protocol-related information that any of the paediatric age groups was to be included in the trial. Interventional trials with medicines were identified in ClinicalTrials.Gov based on type=Drug (which includes agent, pharmaceutical, medications, medicine, medicinal product).

Topics coming soon

  • Expansion cohorts
  • Estimation of outcomes using models instead of hypothesis testing
  • Patient-reported outcomes
  • Alignment of clinical trials and disease burden in children
  • Integrated non-controlled and randomised trials
  • Adaptive trials

Basket trials

In a "basket" trial, there are different arms corresponding to different diseases, thus permitting a broader range of patients to be included. Both, the effects of treatment with a medicine and the susceptibility of the diseases to the treatment may be documented. Methods to design, conduct and analyse such trials vary much and are increasingly discussed .

In ClinicalTrials.Gov, basket trials are identified here by non-randomised allocation to one of at least three arms with largely different labels, not being of a control type, and at least as many conditions as arms. In the plot of the trials, larger symbols are more likely basket trials (based on dissimilarity of conditions and arms).

Randomisation in early phase trials

Randomisation throughout all development phases has recently been recommended when small populations are to be studied such as for personalised medicines , including for possibilities to separate prognostic importance of a biomarker from treatment effects and to faster transition phases.

While a seizable portion of early phase paediatric trials that include randomisation also include randomisation to placebo or to no treatment, it is not yet clear how much such approaches are used across paediatric therapeutic areas.

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Adolescents in "adult" trials

If adolescent patients are included in trials originally planned only for adults, separate and later trials with these paediatric patients may be avoided. Such an age-inclusive approach would build on scientific and medical considerations for the specific trial, and also on general intentions to improve access for these patients and to shorten timelines of developing a medicines of children. Recommendations for oncology were recently put forward by multiple stakeholders . The approach can also be relevant for later phase trials and perhaps other therapeutic areas. Further analyses may be by type of sponsor or by the authorisation status of the medicine.

To track progress with respect to the recommendations, the analysis is limited to the therapeutic area of oncology and to phase 2 trials (search term "cancer" and phase 2 recorded in the EU Clinical Trials Register), because adult phase 1 trials are not be required to be made public in the registers.

However, phase 2 trials may be therapeutic exploratory trials and therefore for a different cancer(s) than in children; therefore, it is expected that only a portion of such trials is relevant for adolescents with a cancer. The number of phase 2 oncology trials open to adolescents seems to be slightly increasing. More analyses will be done on the subset of trials that are for cancers that occur in the paediatric population.

plot of chunk ados_in_adult_trials_oncology

Involvement of paediatric networks

The involvement of paediatric networks is generally recommended to better prepare and conduct trials of medicinal products with children.

Among paediatric trials in the EU Clinical Trials Register with a commercial sponsor (mostly a pharmaceutical company), excluding phase 4 trials, so far a limited proportion (of about 10%) is recorded to involve a (paediatric) network.

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Network name Trials
(recorded to be involved, name not recorded) 171
Medicines for Children Research Network 14
Medicines for Children Research Network MCRN 8
Cystic Fibrosis Foundation 7
Sunovion Pharmaceuticals Inc. 4
Cystic Fibrosis Foundation Therapeutics 4
Innovative Therapies for Children with Cancer ITCC 3
Bristol Myers Squibb 3
Vasculair Research Network VRN 2
TREAT-NMD, The University of Newcastle upon Tyne 2
The Medicines for Children Research Network MCRN 2
Teddy Network 2
Pediatric Rheumatology Collaborative Study Group 2
NIHR Clinical Research Network 2


Gaspar, N., L. V. Marshall, D. Binner, R. Herold, R. Rousseau, P. Blanc, R. Capdeville, et al. 2018. “Joint Adolescent - Adult Early Phase Clinical Trials to Improve Access to New Drugs for Adolescents with Cancer Proposals from the Multi-Stakeholder Platform - ACCELERATE.” Annals of Oncology 29 (3): 766–71.
Herold, Ralf. 2018. Ctrdata: R Package to Aggregate and Analyse Information on Clinical Trials from Public Registers.
Cunanan, Kristen M., Alexia Iasonos, Ronglai Shen, Colin B. Begg, and Mithat Gönen. 2017. “An Efficient Basket Trial Design.” Statistics in Medicine, January, 1568–1579.
Renfro, L. A., and D. J. Sargent. 2017. “Statistical Controversies in Clinical Research: Basket Trials, Umbrella Trials, and Other Master Protocols: A Review and Examples.” Annals of Oncology 28 (1): 34–43.
Saad, Everardo D., Xavier Paoletti, Tomasz Burzykowski, and Marc Buyse. 2017. “Precision Medicine Needs Randomized Clinical Trials.” Nature Reviews Clinical Oncology 14 (5): 317–23.
Chuk, Meredith K., Yeruk Mulugeta, Michelle Roth-Cline, Nitin Mehrotra, and Gregory H. Reaman. 2017. “Enrolling Adolescents in Disease/Target-Appropriate Adult Oncology Clinical Trials of Investigational Agents.” Clinical Cancer Research 23 (1): 9–12.

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