Paediatric Drug Optimization (PADO) report for cancer medicines
19 November 2024
Photo credit: Scott A. Woodward, Persistent Productions, The Global Initiative for Childhood Cancer
The Paediatric Drug Optimization (PADO) process is a strategic approach to identify and prioritise the development of essential paediatric formulations. This report outlines the discussions and outcomes of the PADO process for cancer medicines.
The Need for Paediatric Drug Optimisation
The development of medicines for children lags behind that for adults by around a decade. Since 2016, following the World Health Assembly’s resolution on promoting innovation and access to quality, safe, efficacious, and affordable medicines for children, the World Health Organization (WHO) and its partners have intensified efforts to ensure age-appropriate formulations of essential medicines are available in child-friendly forms.
The Global Accelerator for Paediatric Formulations Network (GAP-f), a WHO-hosted network, accelerates the investigation, development, and introduction of optimal formulations for children. Setting priorities is crucial for a targeted approach to research and development, focusing on the most needed formulations for children. This is particularly important given the small and fragmented market for paediatric medicines.
PADO for Cancer Medicines
Each year, an estimated 400,000 children and adolescents develop cancer. Acute lymphoblastic leukaemia (ALL) is the most common malignancy, followed by non-Hodgkin lymphoma, Burkitt lymphoma, Wilms tumour, and retinoblastoma. In 2022, more than 105,000 children died of cancer, with survival rates varying significantly between high-income and low- and middle-income countries (LMICs).
The Global Initiative for Childhood Cancer (GICC), launched in 2018, aims to achieve a global survival rate of at least 60% by 2030. Following a systematic assessment of the WHO Model List of Essential Medicines for Children (EMLc), the PADO–cancer exercise identified priority formulations for research and development. This initiative aligns efforts among funders, researchers, and manufacturers to address the needs of children with cancer in LMICs.
Overview of Epidemiology and Clinical Management
Childhood cancer is a public health priority, being one of the leading causes of death for children in three of the six WHO regions. Incidence rates are similar globally, but there are minor variations due to over 50 unique types of cancer. Childhood cancer requires a multifaceted response across the health system. In high-income countries (HICs), cancer survival rates have increased to 80–90% due to improvements in care and health systems. The GICC CureAll Framework guides policy-makers and cancer control managers to assess capacities, identify actions, and monitor improvements.
In 2021, WHO and St. Jude Children’s Research Hospital launched the Global Platform for Access to Childhood Cancer Medicines (GPACCM), aiming to provide greater access to cancer medicines for over 120,000 children in 50 countries within five years. This complements the GICC in accelerating progress towards a 60% survival rate by 2030. However, challenges remain, including fragmented markets, inadequate public sector financing, and limited manufacturers.
Pipeline Challenges and Impact on Current Practice
Timely access to promising cancer medicines is a challenge for children in both HICs and LMICs. New agents for cancer in common use in HICs are often out of reach for children in LMICs due to lack of diagnostics, clinical trials, regulatory approvals, and high costs. Improved formulations for paediatric populations in LMICs would lower toxicity and require fewer supportive care needs, leading to better outcomes.
The Need for Better Formulations
Formulating paediatric medicines that address swallowing ability, palatability, and dose flexibility is challenging. Novel formulations such as dispersible tablets, ‘mini’ tablets, and sprinkle dosage forms are increasingly the goal. Cancer medicines have a high toxicity profile, and safe and accurate use is essential. Flexible formulations, packaging, and education are crucial components of paediatric cancer drug development.
Priority-Setting and Watch Lists
The priority-setting process identified eight priority cancer medicines for children during the WHO EMLc review and ten potential priority compounds from the landscape/pipeline analysis. These efforts aim to align funders, researchers, and manufacturers on priority products for investigation and development, addressing the needs of children with cancer in LMICs.
