A Call for Pharmacogenovigilance and Rapid Falsification in the Age of Big Data: Why not First Road Test Your Biomarker?

The conventional drug development paradigm can test new drug candidates only in a limited number of patients and healthy volunteers, typically in the order of a few thousand at most. While the common adverse drug reactions (ADRs) are discerned prior to clinical use, less common or rare ADRs and population-wide efficacy of new drugs are often delineated in greater granularity after regulatory approval in clinical practice. In some cases, serious ADRs may be discovered as long as 36 years after a drug receives regulatory approval (Ladewski et al., 2003). Surveillance of drug safety and efficacy after regulatory approval, pharmacovigilance, is therefore a centerpiece concept in clinical pharmacology and population health. Since the 1970s, governments around the world have established institutions for regulatory science and pharmacovigilance, although they remain cursory in many parts of the developing world. Early signal detection and mechanistic evaluation of ADRs and drug efficacy, not to mention extrapolation of pharmacovigilance data from populationto-population (i.e., population bridging), are areas of active research in rational therapeutics and postgenomics medicine. Health technology assessment (HTA), for example, has led to development of smart decision tools and foresight methods that inform postmarketing surveillance, and are relevant for other health products such as vaccines and nutritional supplements as well. Put in other words, pharmacovigilance aims to understand the epidemiology and mechanisms of vast heterogeneity in drug-related outcomes, be they ADRs or therapeutic outcomes, at an individual and population scale. Pharmacogenomics, another field of 21 century integrative biology, aims to explain the genomics basis individual differences in drug safety and efficacy. The new term pharmacogenovigilance, coined first by Sxardas x in 2010, is defined as ‘‘pharmacovigilance activities informed and guided by accompanying pharmacogenomics analyses.’’ (Sxardas x, 2010). Because both pharmacovigilance and pharmacogenomics share the objective of explaining person-to-person and between-population heterogeneity in drug pharmacokinetics and pharmacodynamics, pharmacogenovigilance buttresses the current efforts for rational and mechanistically informed monitoring of drugs. The integration of pharmacovigilance and pharmacogenomics activities under the rubric of the new field of pharmacogenovigilance offers much conceptual and practical advances, and are described in detail elsewhere (Sxardas x, 2010). For our purposes in this editorial, we wish to emphasize, however, that pharmacogenovigilance by virtue of its incorporation of pharmacogenomics biomarkers, is more mechanistic in its approach to surveillance than traditional pharmacovigilance. Such mechanistic orientation enables