Pharmacogenetics and paediatric drug development: issues and consequences to labelling and dosing recommendations.
The area of pharmacogenetics (PGt) is evolving rapidly. However, ongoing efforts in this field are not aligned with the requirements for the inclusion of clinically relevant findings into the label, especially with reference to paediatric indications. Clinical research in children poses unique issues from a practical and technical perspective, but many challenges can be overcome by applying advanced study design and data analysis methods. When investigating the role of PGt factors on treatment effect, all features that influence drug response must be taken into account. Yet, PGt often has a privileged status in research protocols, with PGt factors evaluated independently from other determinants of response, instead of being regarded as other demographic or clinical covariates (e.g., age, renal function). At present, guidelines to incorporate PGt findings into label statements are lacking in part because this is a new and incompletely understood area. This situation is no longer acceptable. To achieve the potential that PGt can offer to drug development and ultimately to drug prescription, academia, industry and regulatory agencies need to pool resources on the revision of study design and data analysis requisites, bringing in model-based methodologies to enable accurate interpretation of results and provide appropriate labelling recommendations.
Krekels
Elke H J
EH
Clinical Pharmacology & Discovery Medicine, GlaxoSmithKline, Greenford, UK.
van den Anker
John N
JN
Baiardi
Paola
P
Cella
Massimo
M
Cheng
Katharine Y
KY
Gibb
Diana M
DM
Green
Hannah
H
Iolascon
Achille
A
Jacqz-Aigrain
Evelyne M
EM
Knibbe
Catherijne A J
CA
Santen
Gijs W E
GW
van Schaik
Ron H N
RH
Tibboel
Dick
D
Della Pasqua
Oscar E
OE
D000367:Age Factors; D002648:Child; D002986:Clinical Trials as Topic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004348:Drug Labeling; D006801:Humans; D004364:Pharmaceutical Preparations / Q000008:administration & dosage; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012107:Research Design
D004364:Pharmaceutical Preparations