Regulatory approval status of drugs in paediatric cancer trials

Published: October 2023

WHO analysed the current landscape and pipeline of childhood cancer drugs from 2007-July 2022. The drugs identified through this analysis were then investigated further to explore regulatory approval status by European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), including the time intervals between adult and paediatric approvals. 

See also:

What you see | Scope, analysis and limitations | Data sources 

What you see

The data visualization shows the:

• Number of drugs in paediatric cancer trials by regulatory agency approval status (charts A)
• Time intervals between adult and paediatric approval (charts B)
• List of individual cancer drugs with regulatory approval status (chart C)

Points to note:

• Of the drugs currently used in paediatric cancer trials, the majority, 70% for the EMA and 54% for the FDA have not been approved for use in adults or children (charts A).
• Of the drugs currently used in paediatric cancer trials that have received regulatory approval in adults, a minority, only 27% (35/129) for the EMA and 40% (80/196) for the FDA, have been approved for use in children (charts A).
• Only two drugs are approved exclusively for children with cancer by the EMA and only five by the FDA (charts A).
• Of those drugs approved for paediatric use, the mean time intervals from adult approval to paediatric approval for the EMA is 4 years ( range 0-22 years) and for the FDA is 9 years (range 0-58 years)

To explore the data further

• Select a specific approval status (charts A) or any other specific element or combination of elements to display the corresponding data in the other charts. For example, by selecting the 80 cancer drugs that were approved by the FDA in adults and children (chart A.2), we can see on chart A.1 that 28 of them were also approved by the EMA for adults and children, 17 for adults only, and 35 have not been approved in adults or children. (chart A.1). The detailed list of drugs table would also display only those drugs falling in that category.
• Hold the ‘Ctrl’ key on your keyboard to select more than one option. 
• Hover the cursor on a bar or a cell in a table to see more information in a pop-up window. 
• Undo a selection by clicking ‘undo’ or ‘reset’ near the bottom of the page or by clicking the same element again.

Scope, analysis and limitations of the data

Scope

• This analysis focuses on drugs in use in paediatric cancer clinical trials registered over the past 15 years (2007-July 2022).
• Trials were restricted to cancer treatment studies. Registries, biology studies, supportive care studies, psychosocial studies, etc. were excluded. Minimum age of study participants had to be less than 16 years old.

Analysis

• FDA approvals:
  • Not approved:
    • Drugs that are not listed on the Drugs@FDA database and if listed on Inxight, are listed as either investigational or possibly marketed outside of the United States of America.
    • Drugs for which the FDA approval has been withdrawn.
  • Approved in adults and/or children: As listed on the approved product label. Approved labels were located using the Drugs@FDA database and the FDALabel database. Drugs were listed as approved in children if one or more of the following conditions were met:
    • The “Paediatric use” section of the labelling indicated that safety and efficacy is established for paediatric patients.
    • At least one of the labelled indications was listed specifically for paediatric patients/children/adolescents or is listed with a minimum age <18 years.
    • The labelling had dosing information for paediatric populations.
    • The drug was listed on the FDA’s Paediatric Oncology Drug Approvals webpage.
  • Year of adult approval: As listed in the Drugs@FDA Database and the approved product label.
  • Year of paediatric approval: As listed on the FDA's Paediatric Oncology Drug Approvals webpage (if available). Older labels were located using the Drugs@FDA and FDALabel databases, and the DAILYMED Labeling Archive. Labels that were not available online, but were necessary to confirm approval years, were requested through the FDA Freedom of Information Act (FOIA).
• EMA approvals:
  • Not approved:
    • Using the EMA's Medicines database and the European Commission's Public Health - Union Register of medicinal products , drugs were listed as not approved if, in either or both above-mentioned databases, they:
      • Were not listed; or
      • Had only orphan designations listed; or
      • Were listed as nationally authorized or European Commission Final decision (in these instances, “EU-Nationally authorized” was recorded for “Other WLA” given that at least one of the EU member states has approved of the drug).
    • Drugs for which the EMA approval has been withdrawn.
  • Approved in adults and/or children: As listed in the approved European Public Assessment Report (EPAR) - Product information document published on the drug's page in the EMA's Medicines Database. Drugs were listed as approved in children if one or more of the following conditions were met:
    • The “Paediatric population” section of the EPAR indicated that safety, efficacy, and pharmacokinetic profile were established for paediatric patients.
    • At least one of the labelled indications was listed specifically for paediatric patients/children/adolescents or was listed with a minimum age <18 years.
    • The EPAR had dosing information for paediatric populations.
  • Year of adult approval: As listed on the drug's “Authorisation Details” table on the drug's page in the EMA's Medicines Database. Adult approval year was typically the same as the initial approval year unless the drug was exclusively indicated for use in children. Adult approval year was also confirmed using the “Initial marketing-authorisation documents” published for that drug on the EMA's Medicines Database.
  • Year of paediatric approval: The addition of paediatric labelling was discussed in the “Assessment History” documents published on the drug's page in the EMA's Medicines Database. Specifically, the “EPAR - Procedural steps taken and scientific information after authorisation” document, if available, listed the year that paediatric indications were added for that approved drug.

Limitations of the data

Data sources

• International Clinical Trials Registry Platform (ICTRP) 
• Drugs@FDA database
• NIH’s Inxight Drugs database
• FDALabel database 
• FDA’s Pediatric Oncology Drug Approvals webpage 
• DAILYMED Labeling Archives 
• FDA Freedom of Information Act (FOIA) 
• EMA’s Medicines database 
• European Commission's Public Health – Union Register of medicinal products