Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy

Zanden, Tjitske M van der; Smeets, Nori J L; Hoop-Sommen, Marika A. de; Schwerzel, Michiel F.T.; Huang, Hui Jun; Barten, Lieke J.C.; Heijden, Joyce E. M. van der; Freriksen, Jolien J. M.; Horstink, Akira A.L.; Holsappel, Inge; Mooij, Miriam G.; Hoog, Matthijs de; Wildt, Saskia N. de

doi:10.1002/cpt.2736

Cited by 28 publications

(21 citation statements)

References 37 publications

(56 reference statements)

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“…As stated before, the level of evidence for efficacy has been assessed for all drug dosing recommendations in the European Pediatric Formularies. This information, together with information from a literature search on available pediatric PK data, can be used to identify which dosing recommendations can be supported by PBPK modeling [4]. C. Quality of the compound model is a relevant factor to take into consideration when employing the pragmatic approach (see Sect.…”

Section: Moving Forwardmentioning

confidence: 99%

“…Knowledge-based dosing guidelines of the DPF are established based on a careful screening of scientific literature. An analysis of the level of evidence showed that one-third of all dosing recommendations in the DPF is backed by only a low level of evidence (i.e., based on comparative research, non-comparative research or expert consensus) [4].…”

Section: Introductionmentioning

confidence: 99%

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Physiologically Based Pharmacokinetic (PBPK) Model-Informed Dosing Guidelines for Pediatric Clinical Care: A Pragmatic Approach for a Special Population

Freriksen¹,

Heijden²,

Hoop-Sommen³

et al. 2022

Pediatr Drugs

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Physiologically based pharmacokinetic (PBPK) modeling can be an attractive tool to increase the evidence base of pediatric drug dosing recommendations by making optimal use of existing pharmacokinetic (PK) data. A pragmatic approach of combining available compound models with a virtual pediatric physiology model can be a rational solution to predict PK and hence support dosing guidelines for children in real-life clinical care, when it can also be employed by individuals with little experience in PBPK modeling. This comes within reach as user-friendly PBPK modeling platforms exist and, for many drugs and populations, models are ready for use. We have identified a list of drugs that can serve as a starting point for pragmatic PBPK modeling to address current clinical dosing needs. Supplementary Information The online version contains supplementary material available at 10.1007/s40272-022-00535-w.

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Section: Moving Forwardmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Physiologically Based Pharmacokinetic (PBPK) Model-Informed Dosing Guidelines for Pediatric Clinical Care: A Pragmatic Approach for a Special Population

Freriksen¹,

Heijden²,

Hoop-Sommen³

et al. 2022

Pediatr Drugs

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“…The preferred and often most efficient treatment modality in these age groups is a combination of psychotherapy and psychopharmacology, depending on the nature of the symptoms [ 83 ]. While this holds for the pediatric population in general, children and adolescents treated for cancer often suffer from acute and severe manifestations, especially anxiety-related disorders for which immediate interventions are warranted.…”

Section: Clinical Questionsmentioning

confidence: 99%

“…On the contrary, the lack of labeling for a specific disorder, symptom, age group, or dosage does not automatically mean that the use of the drug is inappropriate for that particular use. Instead, it suggests that the inclusion of a specific drug on the label has not been approved by the EMA and/or FDA [ 82 , 83 , 84 , 85 ]. Thus, the responsibilities for the prescription of that therapy rely on the prescriber only.…”

Section: Recommendations and Critical Issuesmentioning

confidence: 99%

The Use of Psychotropic Medication in Pediatric Oncology for Acute Psychological and Psychiatric Problems: Balancing Risks and Benefits

et al. 2022

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Severe acute behavioral and emotional problems represent one of the most serious treatment-related adverse effects for children and adolescents who have cancer. The critical and severe nature of these symptoms often makes necessary the use of psychotropic drugs. A working group composed of experts in multiple disciplines had the task of creating an agreement regarding a management plan for severe acute behavioral and emotional problems (SABEPs) in children and adolescents treated for cancer. To obtain global information on the use of psychotropic drugs in pediatric oncology, the working group first developed and mailed a 15-item questionnaire to many Italian pediatric oncology centers. Overall, an evident lack of knowledge and education regarding the use of psychotropic medications for the treatment of SABEPs was found. Thus, by referring to an adapted version of the Delphi method of consensus and standard methods for the elaboration of clinical questions (PICOs), the working group elaborated evidence-based recommendations for psychotropic drugs in the pediatric oncology setting. Furthermore, based on a thorough multivariate analysis of needs and difficulties, a comprehensive management flow was developed to optimize therapeutic interventions, which allows more accurate and efficient matching of the acute needs of patients while guiding treatment options.

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“…Off-label use constitutes the prescription of a drug outside the prescribing information authorized in the drug label or package insert, including indication, age, dose, formulation, or administration route ( COMMITTEE ON DRUGSNeville et al, 2014 ). Studies have found that 42%–73% of drug prescriptions in patients under 18 years were off-label, with the highest frequencies reported in neonates ( Cuzzolin and Agostino, 2016 ; Hoon et al, 2019 ; Yackey et al, 2019 ; van der Zanden et al, 2022 ). However, off-label use does not mean off-evidence nor does it imply improper or contradicted use ( COMMITTEE ON DRUGSNeville et al, 2014 ; Czaja et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Advancing evidence-based treatment of infectious diseases in children with real-world data: Opportunities and challenges

Radtke

Butte

2023

Front. Pharmacol.

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There is an increased interest in utilizing real-world data (RWD) for pharmaceutical research and regulatory decision-making. The development and use of pediatric medicines could benefit greatly from real-world data studies given nearly half of drugs prescribed to children are “off-label”, meaning there is a lack of pediatric-specific evidence from controlled trials, while there is an abundance of data from routine clinical practice. Currently, the use of real-world data, such as data from electronic health records, is lacking in pediatric research, especially within infectious diseases. Here, we discuss opportunities and challenges for real-world data to generate evidence on the optimal treatment and management of infectious diseases in children.

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Off‐Label, but on‐Evidence? A Review of the Level of Evidence for Pediatric Pharmacotherapy

Cited by 28 publications

References 37 publications

Physiologically Based Pharmacokinetic (PBPK) Model-Informed Dosing Guidelines for Pediatric Clinical Care: A Pragmatic Approach for a Special Population

Physiologically Based Pharmacokinetic (PBPK) Model-Informed Dosing Guidelines for Pediatric Clinical Care: A Pragmatic Approach for a Special Population

The Use of Psychotropic Medication in Pediatric Oncology for Acute Psychological and Psychiatric Problems: Balancing Risks and Benefits

Advancing evidence-based treatment of infectious diseases in children with real-world data: Opportunities and challenges

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