Beyond Genetics—Stratified and Personalised Medicines Using Multiple Parameters

Abstract

Prescribers have been practicing stratified medicine for many years. Patient characteristics, usually non-genetic, including age, comorbidities and concomitant medications are taken into account when deciding which drug to prescribe. In addition, the majority of drugs require dose adjustments across patient subgroups, usually determined by non-genetic differences between the subgroups. Whilst pharmacogenetics hold promise for enhancing treatment stratification and even treatment individualisation, non-genetic factors will continue to be very important. Both non-genetic and genetic factors must be considered to improve understanding and quantification of the variability in treatment outcomes and to guide stratification and targeting of patient subgroups to the right drug and also to the right range of doses within that subgroup. Development of stratified medicines must consider non-genetic as well as genetic factors and, where appropriate, include stratification through optimising the dose for each patient or subgroup as well as by choosing the drug most likely to deliver efficacy to that patient or group.

Associations between statins and adverse events in primary prevention of cardiovascular disease: systematic review with pairwise, network, and dose-response meta-analyses

“…13 This strategy could involve tailoring the type and dosage of statins. 14 Current recommendations on the choice of statin regimen are mainly based on their efficacy in reducing low density lipoprotein cholesterol. 23 Given the different pharmacological mechanisms by which different statins have beneficial and adverse effects, however, classification of the potencies of different types of statins based on their efficacy alone might not be appropriate when considering the safety of treatment.…”

“…One possible solution to improve the use of statins in primary prevention is to apply a stratified treatment strategy, to target optimal treatments in patients with the best trade-off between benefits and harms 13. This strategy could involve tailoring the type and dosage of statins 14. Current recommendations on the choice of statin regimen are mainly based on their efficacy in reducing low density lipoprotein cholesterol 23.…”

Dielectrophoretic analysis of treated cancer cells for rapid assessment of treatment efficacy

“…Cells were suspended at a concentration of 10 6 cells/ml for DEP experiments. Cells were analysed using a 3DEP dielectrophoretic cytometer (DEPtech, Heathfield UK) using 3D “DEP‐wells” and a 2‐min DEP exposure. Spectra were generated using Matlab (The Mathworks, Natick, USA) which presented in values of light intensity versus frequency.…”

“…However, PCR is expensive and slow, and only able to detect single mutations. An alternative approach to stratification involves assessing the wider cellular response to a given intervention . Whilst this is arguably less precise than identification of single genes, there are many incidences where the cell phenotype is more important than its genotype; further, there may be combinations of therapies which may offer an enhanced effect.…”