S5-1_Fiona Russell

© Murdoch Children’s Research Institute, 2020
Why clinical research in the paediatric population
should be a priority
Prof Fiona Russell
Director of Child & Adolescent Health PhD Program, The University of Melbourne,
WHO Collaborating Centre for Child and Neonatal Health Research and Training
Group Leader, Asia-Pacific Health, MCRI
Lead, NHMRC Centre for Research Excellence
Pneumococcal Disease Control in the Asia-Pacific
Chair, Australasian Society of Infectious Diseases
Vaccination Special Interest Group
Co-Chair, World Society of Pediatric
Infectious Diseases
International Scientific Committee
Outline
• The need
• Pandemic
• Vaccines
• Therapeutics
• Non-pharmaceutical measures
• Barriers & potential solutions
The need for paediatric research
• Rates of decline in infant & child mortality have been levelling off since 2015 despite high
or increasing coverage of proven interventions
UNIGME report https://childmortality.org/wp-content/uploads/2023/01/UN-IGME-Child-Mortality-Report-2022.pdf
The need for paediatric research
• Rates of decline of infant and child mortality have
been levelling off since 2015
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The need for paediatric research
• Rates of decline of infant and child mortality have
been levelling off since 2015
• Growing child populations in LMICs
o By 2100, 8 in 10 people will live in Africa or Asia
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The need for paediatric research
• Rates of decline of infant and child mortality
have been levelling off since 2015
• Growing child populations in LMICs
• The investment return for interventions in
young children greatly outweigh the return in
any adult population
(Heckman, Nobel Laureate, Economics)
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The need for paediatric research
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• Rates of decline of infant and child mortality
have been levelling off since 2015
• Growing child populations in LMICs
• The investment return for interventions in
young children greatly outweigh the return in
any adult population
• Prenatal & postnatal health sets a lifelong
trajectory of health & disease
“If we change the beginning of the story, we change
the whole story”
Only 10% of ongoing registered clinical trials include children
International Clinical Trials Registry Platform (ICTRP), October 2023
70% of these are conducted in high income settings
Only 10% in LMICs
International Clinical Trials Registry Platform (ICTRP), October 2023
…where 70% of the under 5 mortality is occurring
Neonatal mortality Child mortality
UNIGME report https://childmortality.org/wp-content/uploads/2023/01/UN-IGME-Child-Mortality-Report-2022.pdf
Only a fraction of global research priorities are
being addressed across the child health domain
Perceived complexity
Active exclusion of children from clinical trials
Few, robust global clinical trial networks to support paediatric research
Pandemic preparedness
must include the needs
of children
Pandemic caused devastating indirect effects- societal
costs unknown, but substantial
Requires “whole person, whole of society” approach
• Must include the developmental needs of children
• School plan
Next pandemic- direct effect on child morbidity &
mortality may be substantial
• Need to be ready with therapeutic, vaccine, NPI trial
platforms
Pandemic- direct effects
• Children mostly spared from direct effects of COVID
• But still a burden esp LMICs
• Brazil
• Disparities in health care, poverty & comorbidities can contribute
to magnifying the burden of COVID-19 in more vulnerable &
socioeconomically disadvantaged children & adolescents
• South Africa
• Admission rate for children <5y higher in 4th wave vs previous
• Overall outcome less severe
• Children with 1+ comorbidity had increased odds of severe
disease, warranting consideration for vaccination Chiwandire et al. PIDJ 2023
Oliveria EA et al, Lancet Child Adol Health, 2021
Traditional vaccine development
Heaton P, NEJM 2020
Timeline for COVID-19 vaccines
versus standard vaccines
COVID-19 vaccines: development, evaluation, approval and monitoring; EMA
Need to ensure
there is a
mechanism to get
to the target
population quickly
• By the time vaccines were available for children, infection-
derived immunity provided similar protection to vaccine-
derived immunity
• Countries who have not vaccinated children now need to
consider whether to vaccinate based on their own context
• Ongoing research priorities for COVID-19 vaccination in
children & adolescents- needs to be part of development plan
• COVID-19 continues to have an impact on children until all
high-risk children are offered vaccination
Pandemic paediatric vaccine trial risk
mitigation • Accelerated development plan that includes
children & adolescents
• First evaluate vaccine platforms with good safety
profile in children (eg. subunit vaccine)
• Adolescents could be included in adult phase
II/III RCTs
• Importance of informed consent
• Undertake stringent RCTs with experienced,
trusted personal
• Phase IV safety studies
• High risk children in the development plan
Therapeutics
“we challenge the notion that therapeutic
trials in children with COVID-19 must await
completion of adult trials”
Risk mitigation
• First evaluate medications already licenced in
children for other conditions
• Use medications that have a reassuring safety
record when used off- label
• Undertake stringent quality safety oversight in RCTs
Non-pharmaceutical
interventions
WHO/UNICEF Guideline
Development Group for mask
guidelines in children
Certainty of evidence low to very low
First WHO Global Clinical Trials Forum- Nov 2023
• Objectives
• Develop a joint vision on strengthening clinical research capabilities aligned with the World
Health Assembly resolution 75.8 (Strengthening clinical trials to provide high-quality evidence
on health interventions and to improve research quality and coordination)
• Discuss how to help build, enhance & sustain functional clinical trial capacity that is used all
the time
• Identify key clinical research networks
• Expected outcomes
• Metrics to enable capacity development of researchers, research institutions, of research
ethics committees, & of national regulatory authorities
• Possible solutions to barriers
Barriers
Common to all areas of research
•DATA & BIOSPECIMEN GOVERNANCE
•RESEARCH LEADERSHIP AND CAPACITY
•INFASTRUCTURE & LOGISTICS
•TRIAL METHODOLOGY
•NATIONAL LEADERSHIP AND STEWARDSHIP
Disproportionately affecting paediatricresearch
• ETHICS and REGULATORY
• FUNDING
• RESEARCH CAPACITY
• Failure of the global research community to efficiently coordinate and
align, including processes between national government, communities,
researchers, regulators, industry and funders to address the most
pressing evidence gaps for infants and children
Risks & benefits
Solutions
WHO Paediatric Working Group-
clinical trials
A coordinated, transparent process with an accountability mechanism to complete high quality
research that provide policy makers with evidence to inform interventions that reduce mortality &
improve health & development
• Over the next 5 years have research collaborations to address agreed research priorities
• High quality evidence to inform policy
• Builds sustainable research infrastructure
• Supported by enabling ethical & regulatory environment
• With accountability mechanism
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Summary
• Impact of the current pandemic on children has been devastating
• Societal impact unknown, but likely to be substantial- can’t happen again
• Can’t afford not to be pandemic ready for paediatric trials
• Ensure high quality paediatric RCT platforms are established in multiple settings & all regions
(including LMICs), with the ability to rapidly pivot in a pandemic
• WHO developing pre-approved generic pandemic protocols (vaccines & therapeutics)
Thank you