Paediatric clinical research in Europe: an insight on experts’ needs and perspectives

Ruggieri, Lucia; Ceci, Adriana; Bartoloni, Franco; Elie, Valéry; Felisi, Mariagrazia; Jacqz-Aigrain, Évelyne; Lupo, Mariangela; Malik, Salma; Manfredi, C.; Reggiardo, Giorgio; Demotes, Jacques; Bonifazi, Donato

doi:10.1016/j.conctc.2021.100735

Cited by 8 publications

(5 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…4. Other regulatory procedures applicable to rare and pediatric conditions have been little considered and may be poorly understood by sponsors and researchers (76). As an example, entrectinib was withdrawn by the Orphan Designation Registry, while it received the PRIME designation followed by an accelerated approval.…”

Section: Discussionmentioning

confidence: 99%

Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed

et al. 2023

Self Cite

View full text Add to dashboard Cite

IntroductionSeveral new active substances (ASs) targeting neuroblastoma (NBL) are under study. We aim to describe the developmental and regulatory status of a sample of ASs targeting NBL to underline the existing regulatory gaps in product development and to discuss possible improvements.MethodsThe developmental and regulatory statuses of the identified ASs targeting NBL were investigated by searching for preclinical studies, clinical trials (CTs), marketing authorizations, pediatric investigation plans (PIPs), waivers, orphan designations, and other regulatory procedures.ResultsA total of 188 ASs were identified. Of these, 55 were considered ‘not under development' without preclinical or clinical studies. Preclinical studies were found for 115 ASs, of which 54 were associated with a medicinal product. A total of 283 CTs (as monotherapy or in combination) were identified for 70 ASs. Of these, 52% were at phases 1, 1/2, and 2 aimed at PK/PD/dosing activity. The remaining ones also included efficacy. Phase 3 studies were limited. Studies were completed for 14 ASs and suspended for 11. The highest rate of ASs involved in CTs was observed in the RAS-MAPK-MEK and VEGF groups. A total of 37 ASs were granted with a PIP, of which 14 involved NBL, 41 ASs with a waiver, and 18 ASs with both PIPs and waivers, with the PIP covering pediatric indications different from the adult ones. In almost all the PIPs, preclinical studies were required, together with early-phase CTs often including efficacy evaluation. Two PIPs were terminated because of negative study results, and eight PIPs are in progress. Variations in the SmPC were made for larotrectinib sulfate/Vitrakvi® and entrectinib/Rozlytrek® with the inclusion of a new indication. For both, the related PIPs are still ongoing. The orphan designation has been largely adopted, while PRIME designation has been less implemented.DiscussionSeveral ASs entered early phase CTs but less than one out of four were included in a regulatory process, and only two were granted a pediatric indication extension. Our results confirm that it is necessary to identify a more efficient, less costly, and time-consuming “pediatric developmental model” integrating predictive preclinical study and innovative clinical study designs. Furthermore, stricter integration between scientific and regulatory efforts should be promoted.

show abstract

Section: Discussionmentioning

confidence: 99%

Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…The availability of trained and well recognized research teams at local, national and European levels remains insufficient ( 33 ). Today, our research team is composed of 3 fulltime pediatricians (two specialized in pediatric pharmacology, particularly needed to design institutional drug trials) and one fellow.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Paediatric Clinical Trial Characteristics and Activity Over 23 Years—Impact of the European Paediatric Regulation on a Single French Clinical Research Center

et al. 2022

View full text Add to dashboard Cite

As unlicensed or off-label drugs are frequently prescribed in children, the European Pediatric Regulation came into force in 2007 to improve the safe use of medicinal products in the pediatric population. This present report analyzes the pediatric research trials over 23 years in a clinical research center dedicated to children and the impact of regulation. The database of trial characteristics from 1998 to 2020 was analyzed. We also searched for differences between two periods (1998–2006 and 2007–2020) and between institutional and industrial sponsors during the whole period (1998–2020). A total of 379 pediatric trials were initiated at our center, corresponding to inclusion of 7955 subjects and 19448 on-site patient visits. The trials were predominantly drug evaluation trials (n = 278, 73%), sponsored by industries (n = 216, 57%) or government/non-profit institutions (n = 163, 43%). All age groups and most subspecialties were concerned. We noted an important and regular increase in the number of trials conducted over the years, with an increased number of multinational, industrially sponsored trials. Based on the data presented, areas of improvement are discussed: (1) following ethical and regulatory approval depending on the sponsor, the mean time needed for administrative and financial agreement, validation of trial procedures allowing trial initiation at the level of the center was 6.3 and 6.5 months (periods 1 and 2, respectively) and should be reduced, (2) availability of expert research teams remain insufficient, time dedicated to research attributed to physicians should be organized and recognition of research nurses is required. The positive impact of the European Pediatric Regulation highlights the need to increase the availability of trained research teams, organized within identified multicenter international pediatric research networks.

show abstract

“…Alguns aspectos fundamentais para a execução de ensaios clínicos pediátricos incluem a preparação de protocolos adequados, investimento e apoio para a realização das pesquisas, e a aplicação de ferramentas como modelagem e simulação ou extrapolação 50 . Para a construção de protocolos que melhor se adequem às preferências da criança e dos pais/responsáveis sugere-se a participação dos mesmos através do emprego de questionários bem elaborados, podendo até mesmo ser aplicados através de plataformas virtuais de discussão, evitando assim a necessidade de deslocamento da família 49 .…”

Section: Iniciativas Para a Melhor Condução De Estudos Clínicos Pediá...unclassified

Medicamentos off-label e não licenciados no âmbito pediátrico: uma revisão descritiva dos últimos dez anos

Balsan

Gobetti

Garcia

2023

CBR

View full text Add to dashboard Cite

A falta de medicamentos contendo bulas prevendo o tratamento de pacientes pediátricos representa um problema frequentemente observado em hospitais, principalmente nos setores de unidade de terapia intensiva (UTI) pediátrica e neonatais. Sabe-se que, para que um tratamento seja considerado seguro e eficaz, uma série de estudos clínicos são necessários, no entanto, relata-se um baixo número dessas pesquisas envolvendo crianças, principalmente devido a questões éticas que dificultam a condução das mesmas. Assim, poucos são os medicamentos que provam ser adequados para o tratamento desses pacientes, tornando necessário recorrer ao uso de medicamentos off-label e não licenciados. Os medicamentos são classificados como off-label quando seu uso se dá de maneira que difere de suas especificações aprovadas, por sua vez, produtos não licenciados são classificados desta forma por não possuírem aprovação para sua comercialização no país ou não possuírem comprovação de segurança e eficácia. O preparo de protocolos de estudo organizados, relato de informações aos pais e à criança de maneira clara e objetiva, aproximação entre pesquisadores e pais para o estabelecimento de uma relação de confiança e a condução das pesquisas em momentos de disponibilidade da família demonstram-se estratégias importantes para facilitar a realização dos ensaios clínicos.

show abstract

Paediatric clinical research in Europe: an insight on experts’ needs and perspectives

Cited by 8 publications

References 15 publications

Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed

Target therapy for high-risk neuroblastoma treatment: integration of regulatory and scientific tools is needed

Analysis of Paediatric Clinical Trial Characteristics and Activity Over 23 Years—Impact of the European Paediatric Regulation on a Single French Clinical Research Center

Medicamentos off-label e não licenciados no âmbito pediátrico: uma revisão descritiva dos últimos dez anos

Contact Info

Product

Resources

About