Paediatric Tools
A series of tools and procedures to support the setup and management of multinational neonatal and paediatric clinical trials in Europe were developed through the PedCRIN project. These tools were created to train and support researchers and clinicians to establish, run, and manage both paediatric and neonatal multinational clinical trials in a more effective and easier way.
Until recently, it was assumed that children reacted to medications as ‘small adults’ and clinical practice focused on adjusting dosage to account for smaller body mass, with the postulation that clinical effects would be equivalent to those observed in adults. Consequently, safety data in the paediatric population cannot necessarily be extrapolated from data in adults because certain adverse drug reactions may only be seen in the paediatric population.
These tools are here to set some guidelines about adverse effects in paediatric clinical trials.
Authors: Donato Bonifazi, Mariagrazia Felisi, Cristina Manfredi, Louise Braken, Matthew Peak, Mark Turner, Rosella Conte, Lucia Ruggieri , Evelyne Jacqz-Aigrain, Beate Aurich, Salma Malik, Christine Kubiak
Abstract: A visual algorithm based on the Naranjo scale and specifically adapted for the paediatric population to help researchers in their assessment of causality of adverse events occurring during a clinical study
V1, 02 APRIL 2021
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Andres Rane, Estelle Naumburg, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool gives examples of potential confounders and risk factors for adverse events/ outcome in neonatal trials
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Outcome
V 1.0, 22 March 2021
In paediatric clinical trials, age reflects changes in pharmacokinetics and pharmacodynamics and factors modifying efficacy and safety. For example a neonate born at 24 weeks gestation does not have the same metabolic capacities as one born at 39 weeks. Similarly, developmental maturation and with it, reference values for laboratory parameters and vital signs change rapidly in neonates. Data collection and analysis needs to take all these factors into account.
The tools are here to set some guidelines about age groups in paediatric clinical trials.
Authors: Evelyne Jacqz-aigrain, Beate Aurich, Valéry Elie, Naura Mahmoudi
Contributors: Andres Rane, Estelle Naumburg, Pascale Wenger, Mark Adams, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool summarises the definitions of commonly used terms for neonatal age-groups
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Age groups
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors:Andres Rane, Estelle Naumburg, Pascale Wenger, Mark Adams,Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool summarises the definitions of commonly used terms for neonatal age-groups
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Age groups, Data collection
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors:Andres Rane, Estelle Naumburg, Pascale Wenger, Mark Adams,Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool proposes a check list for the analysis of age-related data in neonatal trials
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Age groups, Data analysis
V 1.0, 22 March 2021
Conducting PK studies in neonates is challenging because obtaining biological samples (e.g. blood, urine, cerebrospinal fluid) is technically difficult, limited by the volume that can be obtained and the frequency and timing of such samples. Consequently, the number and volume of PK blood samples which can be specifically drawn for a neonatal PK study are limited. Due to these limitations it is not feasible to conduct traditional pharmacokinetics studies in neonates.
These tools are here to set some guidelines about biosamples in paediatric clinical trials.
Authors: Viviana Giannuzzi, Adriana Ceci, Lucia Ruggieri, Rossella Conte, Donato Bonifazi, Mariagrazia Felisi, Cristina Manfredi, Evelyne Jacqz-Aigrain, Beate Aurich, Salma Malik, Christine Kubiak, Andrea Wutte
Abstract: A checklist developed to help researchers, sponsors, and other affiliated personnel actors to verify that all key aspects required to properly manage samples and related data in the context of paediatric trials are taken into consideration
V1, 02 APRIL 2021
Authors: Evelyne Jacqz-Aigrain, Beate Aurich,Valéry Elie, Naura Mahmoudi
Contributors: Saskia De Wildt, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides practical points to consider for neonatal pharmacokinetics studies
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Pharmacokinetics
V 1.0, 22 March 2021
Depending on local legislation, informed consent needs to be provided either by one or both parents/legal guardians. However, independent of the legislation, parents prefer that that consent is sought from both. Parental decisions are strongly influenced by how the information is provided, timing and content.
This tool provides points to consider regarding consent in paediatric clinical trials.
Authors: Evelyne Jacqz-Aigrain, Beate Aurich, Eric Vermeulen, Valéry Elie, Naura Mahmoudi
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides a check list of practical points to consider when talking to parents about the possible inclusion of a neonate into a clinical trial
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Informed consent
Enrolment in neonatal trials is influenced by a variety of factors including protocol design, parental consent and support by health care professionals. Awareness of how the design of various protocol sections may modify the number of enrolled neonates may help improving recruitment. Effective and repeated communication about the trial in the community may for example support the identification of eligible patients and give future parents time to reflect on the possibility to be approached for the inclusion of their child into a clinical trial.
These tools provide points to consider regarding patient's enrolment in paediatric clinical trials.
Authors: Beate Aurich, Eric Vermeulen, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides a list of points to consider during protocol development for improving the enrolment of neonatal trials
Keywords: Neonatal trial, Protocol development, Guidance document, Tool
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool illustrates in a worked example how existing safety data from the product label/ summary of product characteristics can inform exclusion criteria of a neonatal protocol
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Drug safety
V 1.0, 22 March 2021
The feasibility assessment of clinical trials takes into consideration the epidemiology of the neonatal disease, the details of the protocol and trial procedures, amongst others. It may further consider the particularities of trial centres and local/ regional issues (e.g. ethics approval process, informed consent).
These tools provide points to consider regarding feasibility of peadiatric clinical trials.
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Pascale Wenger, Mark Adams, Pirrko Lepola, Jaana Kallio, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool lists examples of points to consider for the feasibility assessment and selection of neonatal centres
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Feasibility
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Pascale Wenger, Mark Adams, Pirrko Lepola, Jaana Kallio, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides points to consider for the feasibility assessment of neonatal study populations
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Feasibility
V 1.0, 22 March 2021
Medicines prescribed to neonates need to have a favourable benefit-risk balance including a formulation adapted to the neonatal population which, for example, limits the risk of medication errors and does not contain excipients which are known to be harmful. Neonatal formulation development is challenging due to rapid maturational changes which may influence pharmacokinetics (PK) and/ or pharmacodynamics (PD), a heterogeneous patient population, common polypharmacy; as well as limits on fluid volume, flow rate of administration, excipients considered to be safe and route of administration. An additional challenge is that the formulation may need to be manipulated to suit neonatal dosing requirements, which may increase the risk of medication errors, lack of efficacy and toxicity.
These tools provide points to consider regarding the formulation of paediatric treatments.
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Pascale Wenger, Mark Adams,Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides a check list of points to consider for excipients in neonatal formulations
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Excipients
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Pascale Wenger, Mark Adams,Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tools lists examples of documents published by regulatory authorities and institutional bodies concerning neonatal formulations
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Formulations, Regulations
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors:Pascale Wenger, Mark Adams ,Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool includes a check list of points to consider for neonatal formulations
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Formulation
V 1.0, 22 March 2021
These tools are basic guides about the way parents and children can be ‘consulted’ about a paediatric clinical study. ‘Consultation’ is asking parents for input about the study. The tool describes a specific way of consultations: a ‘focus group’, a face-to-face meeting. There are other ways to ask patients for input. For example, interviews or questionnaires.
Authors: Cor Oosterwijk, Eric Vermeulen, Mariette H E Driessens
Abstract: This tool is a basic guide about the way parents can be ‘consulted’ about a paediatric clinical study. ‘Consultation’ is asking parents for input about the study. The tool describes a specific way of consultations: a ‘focus group’, a face-to-face meeting.
V1, 06 APRIL 2021
Authors: Cor Oosterwijk, Eric Vermeulen, Mariette H E Driessens
Abstract: This tool is a basic guide about the way children/youth can be ‘consulted’ about a paediatric clinical study. ‘Consultation’ is asking children/youth for input about the study. The tool describes a specific way of consultations: a ‘focus group’, a face-to-face meeting.
V1, 06 APRIL 2021
Clinical trial outcome is defined as a patient’s response to an intervention. It can be assessed in a variety of ways including pharmacokinetics, pharmacodynamics, efficacy and safety using clinical and/or biological parameters. It is recorded for all patients independent of treatment allocation (active and control arm) and can be subjective or objective. The outcome can be assessed by health care providers, patients and observers (i.e. parents) using standardised, validated methods.
These tools provide points to consider regarding the outcomes of paediatric clinical trials.
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool lists examples of data items for the assessment longterm efficacy and safety outcome of neonatal trials
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Long-term outcome
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool lists examples of data items for the assessment shortterm efficacy and safety outcome of neonatal trials
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Short-term outcome
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides examples of data which may inform the planning of data collection and analysis of neonatal outcome
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Outcome data collection, Outcome data analysis
V 1.0, 22 March 2021
During protocol development, drug safety is considered in multiple sections such as the objectives, exclusion criteria as well as safety data collection, reporting and analysis and follow-up. New safety concerns may emerge during the trial or after data lock. These may originate directly from the neonatal trial or may emerge from the literature. Any new safety signal will need careful evaluation of the relevant evidence, including a consideration of any missing data.
These tools provide points to consider regarding protocol development and drug safety in paediatric clinical trials.
Authors: Beate Aurich, Valéry Elie, Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool gives points to consider concerning pharmacovigilance and risk managment at the time neonatal protocol development
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Drug safety
V 1.0, 22 March 2021
Authors: Beate Aurich, Valéry Elie,Naura Mahmoudi, Evelyne Jacqz-Aigrain
Contributors: Andres Rane, Estelle Naumburg, Donato Bonifazi, Salma Malik, Christine Kubiak
Abstract: This tool provides practical points to consider when planning for the analysis of neonatal safety data
Keywords: Neonatal trial, Protocol development, Guidance document, Tool, Safety data collection, Safety data analysis
V 1.0, 22 March 2021