Sean Khozin, Geoffrey Kim & Richard Pazdur in Nature: “….Recent advances in our understanding of disease mechanisms have led to the development of new drugs that are enabling precision medicine. For example, the co-development of kinase inhibitors that target ‘driver mutations’ in metastatic non-small-cell lung cancer (NSCLC) with companion diagnostics has led to substantial improvements in the treatment of some patients. However, growing evidence suggests that most patients with metastatic NSCLC and other advanced cancers may not have tumours with single driver mutations. Furthermore, the generation of clinical evidence in genomically diverse and geographically dispersed groups of patients using traditional trial designs and multiple competing therapies is becoming more costly and challenging.
Strategies aimed at creating new efficiencies in clinical evidence generation and extending the benefits of precision medicine to larger groups of patients are driving a transformation from a reductionist approach to drug development (for example, a single drug targeting a driver mutation and traditional clinical trials) to a holistic approach (for example, combination therapies targeting complex multiomic signatures and real-world evidence). This transition is largely fuelled by the rapid expansion in the four dimensions of biomedical big data, which has created a need for greater organizational and technical capabilities (Fig. 1). Appropriate management and analysis of such data requires specialized tools and expertise in health information technology, data science and high-performance computing. For example, efforts to generate clinical evidence using real-world data are being limited by challenges such as capturing clinically relevant variables from vast volumes of unstructured content (such as physician notes) in electronic health records and organizing various structured data elements that are primarily designed to support billing rather than clinical research. So, new standards and quality-control mechanisms are needed to ensure the validity of the design and analysis of studies based on electronic health records.