Commentary: What Can We Really Learn From Observational Studies?: The Need for Empirical Assessment of Methodology for Active Drug Safety Surveillance and Comparative Effectiveness Research

In 2007, the US Congress passed the Food and Drug Administration (FDA) Amendment Act, which called for the establishment of an “active postmarket risk identification and analysis system” with access to data from 100 million people by 2012. The American Recovery and Reinvestment Act of 2009 committed $1.1 billion to comparative effectiveness research (CER), to enable “the conduct and synthesis of research comparing the benefits and harms of different interventions and strategies to prevent, diagnose, treat, and monitor health conditions in ‘real world’ settings.” Both developments rely on expanded secondary use of observational healthcare data, and have thrust the field of epidemiology into the national spotlight. In particular, these efforts require a significant evolution in the use of these data from the customized design of an individual study of a particular product-outcome association to a broader effort that effectively uses these data for active monitoring of any medical product and any health outcome of interest across a network of disparate databases. The envisioned systems would go beyond the retrospective evaluation of hypothesized effects. Researchers would have the opportunity to proactively explore the data to generate and refine hypotheses of potential issues and benefits that warrant further scrutiny. Little research currently exists to inform the development of such systems. Focusing just on active drug safety surveillance, open questions include the following: