Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example

A. Arzimanoglou, L. Kalilani, M. A. Anamoo, M. Cooney, A. Golembesky, C. Taeter, A. Bozorg, A. Tofighy, James Wheless

Research output: Contribution to journalArticle

Abstract

Extrapolation of efficacy data from adults to children is accepted for focal epilepsy – the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.

Original languageEnglish (US)
Pages (from-to)589-603
Number of pages15
JournalEuropean Journal of Paediatric Neurology
Volume23
Issue number4
DOIs
StatePublished - Jul 1 2019

Fingerprint

Observational Studies
Epilepsy
Seizures
Partial Epilepsy
Generalized Epilepsy
Pediatrics
lacosamide
Anticonvulsants
Outcome Assessment (Health Care)
Safety
Therapeutics

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

Cite this

Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example. / Arzimanoglou, A.; Kalilani, L.; Anamoo, M. A.; Cooney, M.; Golembesky, A.; Taeter, C.; Bozorg, A.; Tofighy, A.; Wheless, James.

In: European Journal of Paediatric Neurology, Vol. 23, No. 4, 01.07.2019, p. 589-603.

Research output: Contribution to journalArticle

Arzimanoglou, A. ; Kalilani, L. ; Anamoo, M. A. ; Cooney, M. ; Golembesky, A. ; Taeter, C. ; Bozorg, A. ; Tofighy, A. ; Wheless, James. / Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example. In: European Journal of Paediatric Neurology. 2019 ; Vol. 23, No. 4. pp. 589-603.
@article{7163c463cf4047cfa8b536f80936fd3b,
title = "Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example",
abstract = "Extrapolation of efficacy data from adults to children is accepted for focal epilepsy – the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.",
author = "A. Arzimanoglou and L. Kalilani and Anamoo, {M. A.} and M. Cooney and A. Golembesky and C. Taeter and A. Bozorg and A. Tofighy and James Wheless",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.ejpn.2019.05.002",
language = "English (US)",
volume = "23",
pages = "589--603",
journal = "European Journal of Paediatric Neurology",
issn = "1090-3798",
publisher = "W.B. Saunders Ltd",
number = "4",

}

TY - JOUR

T1 - Role of observational studies in supporting extrapolation of efficacy data from adults to children with epilepsy — A systematic review of the literature using lacosamide as an example

AU - Arzimanoglou, A.

AU - Kalilani, L.

AU - Anamoo, M. A.

AU - Cooney, M.

AU - Golembesky, A.

AU - Taeter, C.

AU - Bozorg, A.

AU - Tofighy, A.

AU - Wheless, James

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Extrapolation of efficacy data from adults to children is accepted for focal epilepsy – the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.

AB - Extrapolation of efficacy data from adults to children is accepted for focal epilepsy – the antiepileptic drug, lacosamide, has been approved for the treatment of children ≥4 years of age on this basis. Since many small-scale, open-label studies are reported in the literature before approval, a systematic review was conducted to ascertain whether results of these could be used to support extrapolation in epilepsy in the future. In the absence of randomised trials, a second analysis was conducted for reports on lacosamide use in adults with generalized epilepsies. Twenty-seven articles were included in the paediatric qualitative synthesis, and 14 in the adult. Paediatric studies were analysed separately based on seizure type: focal, generalised and mixed. In focal epilepsy, safety and seizure-related findings mirrored those observed in the adult Phase II/III trials, supporting the feasibility of data extrapolation. Few studies reported outcomes in children with epilepsies associated with generalised seizures, and those that included children with different seizure types, mostly did not provide results separately. Lacosamide treatment appeared beneficial for children and adults experiencing tonic-clonic and myoclonic seizures. Reports of seizure aggravation were inconsistent and, in many cases, could not be clearly attributed to lacosamide. Given the absence of sufficient data, evidence for the feasibility of extrapolation was not as clear-cut as it was in focal epilepsy. These results highlight the complexities of conducting trials in the generalised epilepsy setting, and the importance of studies in the real-life setting and of analysing efficacy data per generalized seizure type and syndrome.

UR - http://www.scopus.com/inward/record.url?scp=85066402740&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85066402740&partnerID=8YFLogxK

U2 - 10.1016/j.ejpn.2019.05.002

DO - 10.1016/j.ejpn.2019.05.002

M3 - Article

VL - 23

SP - 589

EP - 603

JO - European Journal of Paediatric Neurology

JF - European Journal of Paediatric Neurology

SN - 1090-3798

IS - 4

ER -