Defining drug response for stratified medicine.
The premise for stratified medicine is that drug efficacy, drug safety, or both, vary between groups of patients, and biomarkers can be used to facilitate more targeted prescribing, with the aim of improving the benefit:risk ratio of treatment. However, many factors can contribute to the variability in response to drug treatment. Inadequate characterisation of the nature and degree of variability can lead to the identification of biomarkers that have limited utility in clinical settings. Here, we discuss the complexities associated with the investigation of variability in drug efficacy and drug safety, and how consideration of these issues a priori, together with standardisation of phenotypes, can increase both the efficiency of stratification procedures and identification of biomarkers with the potential for clinical impact.
Division of Cardiovascular & Diabetes Medicine, University of Dundee, Dundee DD1 9SY, UK.
Mike
M
Lonergan
Competence Center in Methodology and Statistics, (CRP-Santé) 1A-B, Rue Thomas Edison, L-1445 Strassen, Luxembourg.
Stephen J
SJ
Senn
Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool L69 3GL, UK.
Christine
C
McNamee
Institute of Cellular Medicine, Newcastle University, Newcastle NE2 4HH, UK.
Ann K
AK
Daly
NIHR Liverpool Pancreas Biomedical Research Unit, University of Liverpool, Liverpool L69 3GA, UK.
Robert
R
Sutton
Northcote House, University of Exeter, Exeter EX4 4QJ, UK.
Andrew
A
Hattersley
Division of Cardiovascular & Diabetes Medicine, University of Dundee, Dundee DD1 9SY, UK.
Ewan
E
Pearson
Wolfson Centre for Personalised Medicine, University of Liverpool, Liverpool L69 3GL, UK. Electronic address: munirp@liverpool.ac.uk.
Munir
M
Pirmohamed
D054316:Biomarkers, Pharmacological / Q000032:analysis*; D002986:Clinical Trials as Topic; D016903:Drug Monitoring / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D058990:Molecular Targeted Therapy; D010597:Pharmacogenetics; D057285:Precision Medicine / Q000379:methods*; D012107:Research Design
D054316:Biomarkers, Pharmacological