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Nat Rev Cardiol. 2015 Aug;12(8):475-87. doi: 10.1038/nrcardio.2015.64. Epub 2015 May 5.

Genotype-based clinical trials in cardiovascular disease.

Author information

Division of Cardiovascular Diseases, Department of Internal Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Department of Biomedical Statistics and Informatics, Health Sciences Research, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Peter Munk Cardiac Centre and Heart and Stroke Richard Lewer Centre, University of Toronto, 585 University Avenue, Toronto, ON M5G 2N2, Canada.


Consensus practice guidelines and the implementation of clinical therapeutic advances are usually based on the results of large, randomized clinical trials (RCTs). However, RCTs generally inform us on an average treatment effect for a presumably homogeneous population, but therapeutic interventions rarely benefit the entire population targeted. Indeed, multiple RCTs have demonstrated that interindividual variability exists both in drug response and in the development of adverse effects. The field of pharmacogenomics promises to deliver the right drug to the right patient. Substantial progress has been made in this field, with advances in technology, statistical and computational methods, and the use of cell and animal model systems. However, clinical implementation of pharmacogenetic principles has been difficult because RCTs demonstrating benefit are lacking. For patients, the potential benefits of performing such trials include the individualization of therapy to maximize efficacy and minimize adverse effects. These trials would also enable investigators to reduce sample size and hence contain costs for trial sponsors. Multiple ethical, legal, and practical issues need to be considered for the conduct of genotype-based RCTs. Whether pre-emptive genotyping embedded in electronic health records will preclude the need for performing genotype-based RCTs remains to be seen.

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