Genome Variations in the Design of Informed Clinical Trials

Although pharmacogenetics is a relatively new field of study, it has already made a significant contribution to the standard treatment options for several common cancers. However, it is the positive impact that this science can have on the clinical development processes of potential new cancer therapies that is of greatest interest to companies working in this space.


Prior to the mapping of the human genome just over a decade ago, participants were recruited into oncologic clinical trials predominantly on indication. This would typically involve a clinical diagnosis followed by confirmation of the tumour type via histopathology. The use of pharmacogenetic technology takes this one giant step further. By detecting small variations in genome DNA, the most common of which are single polymorphisms, subsets of patients within a primary indication can be identified. These molecular variations can influence how a drug is metabolised and the extent of adverse events may be experienced. As they can even impact on common endpoints including progression free and overall survival rates, the benefits of pharmacogenetics to drug development can’t be overstated.


In the experience of Southern Star Research, an increasing number of oncology trials conducted on behalf of clients include pharmacogenetic testing. It is typically used to confirm patient eligibility in the first instance before allowing the stratification of trial subjects during data analysis. Ultimately this helps to determine the differences in response to the investigational product across subsets of subjects whilst providing insight into the preferred dosing range to ensure an appropriate risk/benefit profile. Certainly, without consideration of the pharmacogenetic impacts, clinical trial data analysis runs the risk of generating generic conclusions on the safety and efficacy of an investigational therapy across a diagnosis. The positive impacts achieved in one particular subset may be diluted, if not concealed, by data from non-responding subsets. The financial, social and therapeutic implications of this can be detrimental to the development of new therapies.  Most importantly, it could prevent the commercialisation of potentially life-saving treatment options that could be invaluable to a percentage of the patient population.


By having an understanding of how individuals may be affected by therapies based on the presence of particular molecular variations, pharmacogenetics offers the ability to design more informed trials. The follow-on effect of this is the identification and assessment of targeted cancer therapies in a faster, safer and more cost-effective way.