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5 Key Considerations for Planning Paediatric Clinical Trials in the EU

August 2, 2021

According to the European Medicines Administration (EMA), approximately 50% of all medications routinely used in children lack a specific Paediatric Use Marketing Authorisation (PUMA). As a result, paediatricians often need to adapt adult dosages or indications to the best of their ability or use off-label medications to treat children.

Gathering verifiable data about a drug’s efficacy and safety level in children requires conducting additional paediatric clinical trials. Such studies must meet stricter regulatory, safety, and ethical requirements. Before conducting these trials, Sponsors must first submit a Paediatric Investigation Plan (PIP), which the EMA’s Paediatric Committee must approve.

Why is a PIP Required?

A PIP is one of the most important documents required to obtain a PUMA, as it will allow the Paediatric Committee (PDCO) to examine the protocols and methods that will be used when performing studies in children. Currently, submitting a PIP is required to obtain marketing authorisations for:

  • All new medications, unless exempted for specific reasons
  • Existing drugs seeking to add a new indication
  • Existing medicines pursuing a new presentation or route of administration

What is the PIP?

A PIP is a developmental plan that must be submitted electronically to the EMA. Then, it needs to be reviewed and approved by the PDCO before starting a paediatric clinical trial.

The methods described in the PIP are considered binding. After a Sponsor and the PDCO agree on a Paediatric Investigation Plan, the information gathered during these trials will be presented as part of the general marketing authorisation process. 

Considerations to Formulate a High-Quality PIP

A PIP is a lengthy file that needs to cover a detailed list of information, accompanied by all supporting documentation. 

Although the PDCO makes a “PIP Template” available on its website, preparation of the package can take many months and requires the assistance of experienced medical writers.

The following five factors can help formulate a high-quality PIP and minimise the need for revisions and amendments.

1. Deadlines

The PDCO routinely meets once a month. However, the deadline to submit the PIP is usually 2 to 3 months before the meeting in which it will be discussed. During this meeting, the PDCO may approve, reject, or request modifications on the PIP. 

As the PIP submission package can take many months to prepare, it is crucial to begin the process early and allocate the necessary resources to complete it in time. 

2. The complexity of the submissions package

The PIP template requires an explanation of the possible differences in how the condition presents itself in paediatric and adult patients. It should also explain the need for a new IMP by comparing its mechanism of action with the medications currently approved to treat or prevent this condition. 

However, the core section of a PIP will list the overall strategy that will be used during the investigation. This should include any ongoing quality, clinical and non-clinical paediatric studies and an outline for the protocols of any planned studies.

3. Paediatric subsets and their specific formulations

The EMA recognises five separate paediatric subsets, based on age:

  • Preterm newborns
  • Term newborns, less than a month old
  • Infants and toddlers, between one month and two years old
  • Children aged 2 to 11 years old
  • Adolescents aged 12 to 16 years old

The different strategies, dosages and formulations used with each one of these categories should consider the patient’s stage of development and the possibility of long-impacting adverse reactions. 

In some cases, it may be impossible to ensure minimum safety standards for a specific age bracket, or the disease may not occur in children of that age. In such cases, Sponsors may apply for a product or population-specific waiver.

4. The possible need for Scientific Advice

A request for Scientific Advice offers an opportunity to ask specific questions to a regulatory agency to help develop a more robust or safer protocol. 

Requests for Scientific Advice usually carry a fee. However, the EMA has waived the fee for Scientific Advice requests for studies in children. This is part of their efforts to promote the development of safe, well-regulated paediatric clinical trials.

5. Data and Safety Monitoring Committees

When presenting a PIP, Sponsors should expect the PDCO to pay great attention to any internal mechanisms implemented to safeguard the safety of the participants. 

Enlisting a third-party data and safety monitoring committee is not mandatory for PIP approval. However, their involvement can help build a more substantial submission or implement more efficient reporting systems for any possible adverse events.

How Dokumeds can help

These five key points can provide a solid foundation to begin building a solid PIP. However, there are other aspects at play when seeking approval for a trial involving children. 

Dokumeds has 23 years of experience working with paediatric clinical trials. Over the past 5 years, we have conducted 14 trials in children across 15 different countries.  Because of this, our staff possess valuable insights into the PIP preparation process. Our e-book will provide you with more in-depth strategies to help you gain regulatory approval.

Paediatric Clinical Trials in the EU: How to Overcome Regulatory and Ethical Challenges

There is a high need to get more medications authorized for paediatric use.
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