Pharmacogenomics, Theranostics and Personalized Medicine - the complexities of clinical trials: challenges in the...

While the potential for the application of pharmacogenomics and theranostics to develop personalized healthcare solutions is enormous, multiple challenges will need to be addressed to get there. Understanding the complex interactions and detailed characterization of the functional variants of individual ADME (Absorption Distribution Metabolism Excretion) genes and drug target genes is needed to demonstrate clinical utility, using both a bottoms-up as well as a top-down approach. Clinical trials need to be designed appropriately so as to identify not only individual but also population variations. The impact of non-genetic and environmental factors, epigenetic variations and circadian rhythms on an individual's response need to be assessed to make pharmacogenomics clinically indicated. More advanced algorithms and appropriate study designs need to be developed to allow this pipeline to grow and to be used effectively in the clinical setting. Another challenge lies in the value proposition to the pharmaceutical industry. Fearing the impact of the slice and dice approach on revenues, companies are going slow on developing pharmacogenomic solutions; yet many are hedging their bets, amassing huge amounts of single nucleotide polymorphisms (SNP) data. They are being used as predictors of drug efficacy and safety to zero in on subpopulations that are at risk for either a bad response or no response in clinical trials, supporting the Fail fast, Fail cheap approach. In addition, the growth of theranostics is impeded by the fear that the approval of both the diagnostic and the drug would get delayed. Education of the health care provider, payor, regulator and the patient is also required and an exercise of change management needs to occur. Countries such as India should exploit the joint benefit of the reduced cost of tests today, complemented by a large and a highly genetically diverse population.