Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

Christiansen, Helle; Bruin, Marie L De; Frøkjær, Sven; Hallgreen, Christine Erikstrup

doi:10.1371/journal.pone.0266353

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…To date there is still a huge need of appropriate and consistent regulatory information for the use of available psychotropic drugs in children and adolescents. We have shown that such use of available drugs is far from being rare, but this off-label use is currently done empirically and in the absence of the regulatory guarantees that are granted through strict product labelling processes (Christiansen et al, 2022). The present study provide an overview on the psychotropic use and highlights that pediatric patients are in need of special attention.…”

Section: Off-label Use Of Psychotropicsmentioning

confidence: 87%

Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

et al. 2023

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Psychotropics are increasingly used in pediatrics, often as off-label medicines. The guarantees of safety and efficacy are not always granted in clinical practice compared to adult authorised indications. A retrospective observational study was done to estimate the prevalence of psychotropic use in pediatric subjects of Catalonia (Spain). Anonymised data on dispensation of psychotropics to pediatric patients, demography and other related data were obtained by the local healthcare management for the period 2008–2017. Estimation of off-label use was done through description of drug dispensations with no authorised use related to age range. The prevalence of psychotropics was 40.8–64.2 per 1,000 pediatric inhabitants. Hydroxyzine-only represented two-thirds of dispensations, and when removed, the prevalence dropped to 26.4–32.2 per 1,000 pediatric inhabitants. Adolescents and boys were more likely to receive a psychotropic. Psychostimulants had the highest exposure rate, mainly due to methylphenidate. Off-label use was observed in 12% of subjects, corresponding to 4.6% of all dispensed psychotropics with boys being more exposed. The proportion of off-label use vs. labelled use was higher in younger populations. Aripiprazole had the highest off-label frequency. Our data support the frequent reality of off-label use in pediatrics, despite the potential underestimation related to the selected off-label definition. There is an urgent need to systematically ascertain effectiveness and any potential adverse events in the off-label pediatric setting, and to generate valuable information for risk-benefit assessment in these populations where extrapolation from adults is not reliable.

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Section: Off-label Use Of Psychotropicsmentioning

confidence: 87%

Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

et al. 2023

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“…In general, it has been shown that the US FDA grants more orphan drug designations as compared to the EMA ( 23 ) and therefore, the exemption could have a rather large impact. However, a recent study with a similar study sample, found only a few discrepancies between the guidance for pediatric use in the prescription information ( 24 ), suggesting that the impact of the observed differences in requirements on the regulatory output is rather small. There could be several reasons for this.…”

Section: Discussionmentioning

confidence: 96%

Mandatory requirements for pediatric drug development in the EU and the US for novel drugs—A comparative study

2022

Self Cite

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Mandatory pediatric legislation has been implemented in the European Union (EU) and the United States (US) to increase research and the availability of drugs for the pediatric population. Differences in the legislative framework can cause different pediatric requirements for similar indications granted for similar drugs across jurisdictions. This cross-sectional study compares the pediatric requirements for therapeutic indications granted at the time of initial approval for novel drugs approved in the two regions from 2010 to 2018. We collected the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) decisions to grant a waiver and/or to agree on a pediatric development plan and deferrals hereof at marketing authorization (MA) from publicly available documents. An agreed pediatric development plan was required for 66% (N = 188/285) and 63% (N = 134/212) of the indications granted in the EU and the US at the time of approval, respectively. Almost all (EU; 98%, US; 89%) were deferred until after MA. Based on the broad scope of the EU Pediatric Regulation, an additional 36 PIPs originated from the indications granted at MA. In the subset of indications granted for drugs approved in both the EU and the US (N = 232), significantly more indications resulted in an agreed pediatric development plan for one or more subsets of the pediatric population in the EU (N = 185) as compared to the US (N = 82). This was based on the exemption of orphan designated drugs in the US and the broader scope of the EU Pediatric Regulation. However, indications subject to the mandatory pediatric legislation in both regions (N = 131) most often had similar regulatory requirements for the inclusion of the pediatric population from the EMA and the US FDA (83%, N = 109). In conclusion, when comparing mandatory pediatric requirements, more pediatric development plans were agreed upon in the EU than in the US, in line with the broader mandates of the EU Pediatric Regulation. However, authorities most often had similar regulatory requirements when an indication was subject to pediatric legislation in both regions.

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“…Previous studies have shown that most drugs approved for adults continue to enter the market without pediatric information and lack pediatric prescribing data for extensive periods, even after PREA is implemented, owing to poor compliance with the submitted pediatric assessment plan [22]. Moreover, the scope difference in mandatory pediatric assessment requirements did not in uence prescription information for pediatric use between the US and Europe, although the EU pediatric regulations provided a broader mandate for pediatric drug development [23]. Our ndings align with those of previous studies, suggesting a different regulation of whether mandating pediatric development did not signi cantly affect prescription information for pediatric use between Japan and the US, where there is no legislation mandating pediatric assessments.…”

Section: Discussionmentioning

confidence: 99%

Pediatric-specific drug loss issue in Japan: Comparison of pediatric development status between Japan and the United States

Osako,

Matsumaru,

Tsukamoto

2024

Preprint

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Background The lack of label information for the pediatric population has been a global issue, leading to the introduction of several countermeasures by major health authorities. Despite various efforts by Japanese health authorities, some drugs are approved only for adults in Japan, while the US label includes information on pediatric usage for the same drugs. This suggests a potential for pediatric-specific drug loss in Japan, where overall drug loss has recently become a major concern. Methods In this study, we compared the pediatric usage status between Japan and the US, focusing on the indications approved in both countries. Results We found that the proportion of indications, including pediatric usage, was significantly higher in the US than in Japan. Multivariate analysis of indications for pediatric usage in the US demonstrated that US-first development and non-simultaneous development with adults had a negative impact on the inclusion of pediatric usage in Japan; however, the pediatric assessment request on the grounds of US legislation was not a significant factor. For pediatric indications approved solely in the US, most relied on multi-regional clinical trial data that included the US but excluded Japan. Conclusions Our results suggest that there was pediatric-specific drug loss in Japan compared to that in the US. Further frameworks to promote pediatric drug development should be introduced in Japan to address pediatric-specific drug loss issues.

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Guidance for pediatric use in prescription information for novel medicinal products in the EU and the US

Cited by 4 publications

References 22 publications

Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

Utilisation of drugs for the treatment of psychiatric diseases in the pediatric population: focus on off-label use

Mandatory requirements for pediatric drug development in the EU and the US for novel drugs—A comparative study

Pediatric-specific drug loss issue in Japan: Comparison of pediatric development status between Japan and the United States

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