Paediatric drug development and evaluation: Existing challenges and recommendations

Florentia Kaguelidou; Maria Ouèdraogo; Jean-Marc Treluyer; Claire Le Jeunne; Maxime Annereau; Patricia Blanc; Serge Bureau; Stéphane Ducassou; Béatrice Fiquet; Florence Flamein; Ségolène Gaillard; Regis Hankard; Vincent Laugel; Corinne Laurent; Corinne Levy; Thierry Marquet; Michel Polak; Aurélie Portefaix; Gilles Vassal

doi:10.1016/j.therap.2022.11.010

Paediatric drug development and evaluation: Existing challenges and recommendations

Therapie. 2023 Jan-Feb;78(1):105-114. doi: 10.1016/j.therap.2022.11.010. Epub 2022 Dec 5.

Authors

Florentia Kaguelidou¹, Maria Ouèdraogo², Jean-Marc Treluyer³, Claire Le Jeunne⁴, Maxime Annereau⁵, Patricia Blanc⁶, Serge Bureau⁷, Stéphane Ducassou⁸, Béatrice Fiquet⁹, Florence Flamein¹⁰, Ségolène Gaillard¹¹, Regis Hankard¹², Vincent Laugel¹³, Corinne Laurent¹⁴, Corinne Levy¹⁵, Thierry Marquet¹⁶, Michel Polak¹⁷, Aurélie Portefaix¹⁸, Gilles Vassal¹⁹

Affiliations

¹ Center of Clinical Investigations and Pediatric Pharmacology, Inserm CIC1426, Robert-Debré hospital, AP-HP.Nord, 75000 Paris, France; Paris Cité University, EA7323 « Therapeutic assessment, and perinatal and pediatric pharmacology », 75000 Paris, France. Electronic address: florentia.kaguelidou@aphp.fr.
² Lead « partenaires parcours de soins référents médicaux », laboratoire Roche, 92100 Boulogne, France.
³ Paris Cité University, EA7323 « Therapeutic assessment, and perinatal and pediatric pharmacology », 75000 Paris, France; Département de pharmacologie, CRPV, hôpital Cochin, AP-HP.Centre, 75014 Paris, France.
⁴ Paris Cité University, EA7323 « Therapeutic assessment, and perinatal and pediatric pharmacology », 75000 Paris, France; Service de médecine interne, hôpital Cochin, AP-HP Centre, 75014 Paris, France.
⁵ Département de pharmacie clinique, Gustave Roussy Cancer Campus, 94800 Villejuif, France.
⁶ Association de patients («) Imagine for Margo - Enfants sans Cancer », 78100 Saint-Germain-en-Laye, France.
⁷ Direction de la recherche clinique, de l'innovation, des relations avec les universités et organismes de recherche (DRCI), Assistance publique-Hôpitaux de Paris, 75000 Paris, France.
⁸ Unité hématologie oncologie pédiatrique, CHU Bordeaux, 33000 Bordeaux, France.
⁹ Département médical, Amgen, 92100 Boulogne-Billancourt, France.
¹⁰ University Lille, Inserm, CHU Lille, CIC-1403 Inserm-CHU, 59000 Lille, France; French Clinical Research Infrastructure Network (F-CRIN) - PEDSTART, 94000 Créteil, France.
¹¹ Hospices civils de Lyon, EPICIME-CIC 1407 de Lyon, Inserm, CHU-Lyon, 69677 Bron, France; Université Lyon 1, CNRS UMR 5558, laboratoire de biométrie et biologie évolutive, 69622 Villeurbanne, France.
¹² Inserm, F-CRIN PEDSTART, 37000 Tours, France.
¹³ Pôle médico-chirurgical de pédiatrie, centre d'investigation clinique, hôpitaux universitaires de Strasbourg, 67098 Strasbourg, France.
¹⁴ Novartis, 92563 Rueil-Malmaison, France.
¹⁵ Clinical Research Center (CRC), centre hospitalier intercommunal de Créteil, 94000 Créteil, France.
¹⁶ Accès des patients à l'innovation, Takeda, 75116 Paris, France.
¹⁷ Unité d'endocrinologie, gynécologie, diabétologie pédiatriques, Inserm U1016, Institut Imagine, centre de référence des maladies endocriniennes rares de la croissance et du développement, hôpital universitaire Necker-Enfants-Malades, AP-HP Centre, université Paris-Descartes, 75743 Paris, France.
¹⁸ Hospices civils de Lyon, Pediatric Clinic Investigation Center, Inserm P-1407, 69500 Bron, France.
¹⁹ Département de cancérologie de l'enfant et de l'adolescent, Gustave Roussy Comprehensive Cancer Center et université Paris-Saclay, 94805 Villejuif, France.

PMID: 36528416
DOI: 10.1016/j.therap.2022.11.010

Abstract

Despite various international regulatory initiatives over the last 20 years, many challenges remain in the field of paediatric drug development and evaluation. Indeed, drug research and development is still focused essentially on adult indications, thereby excluding many paediatric patients, limiting the feasibility of trials and favouring competing developments. Off-label prescribing persists and the development of age-appropriate dosage forms for children remains limited. Against this background, the members of this panel (TR) recommend the launch of multi-partner exchange forums on specific topics in order to focus new drug research and development on the real, unmet medical needs of children and adolescents, and in keeping with the underlying mechanisms of action. Scientific information sharing and cooperation between stakeholders are also essential for defining reference evaluation methods in each medical field. These forums can be organised through existing paediatric facilities and research networks at the French and European level. The latter are specifically dedicated to paediatric research and can facilitate clinical trial implementation and patient enrolment. Moreover, specific grants and public/private partnerships are still needed to support studies on the repositioning of drugs in paediatric indications, and pharmacokinetic studies aimed at defining appropriate dosages. The development of new pharmaceutical forms, better suited for paediatric use, and the promotion of resulting innovations will stimulate future investments. Initiatives to gather observational safety and efficacy data following off-label and/or derogatory early access should also be encouraged to compensate for the lack of information available in these situations. Finally, the creation of Ethics Committees (EC) with a specific "mother-child" advisory expertise should be promoted to ensure that the current regulation (Jardé law in France) is implemented whilst also taking into account the paediatric specificities in medical trials.

Keywords: Challenges; Clinical trials; Drug development; Innovation; Paediatrics.

MeSH terms

Adolescent
Adult
Child
Drug Development*
Forecasting
France
Humans