External validity in distributed data networks.

PURPOSE

While much has been written about how distributed networks address internal validity, external validity is rarely discussed. We aimed to define key terms related to external validity, discuss how they relate to distributed networks, and identify how three networks (the US Food and Drug Administration's Sentinel System, the Canadian Network for Observational Drug Effect Studies [CNODES], and the National Patient Centered Clinical Research Network [PCORnet]) deal with external validity.

METHODS

We define external validity, target populations, target validity, generalizability, and transportability and describe how each relates to distributed networks. We then describe Sentinel, CNODES, and PCORnet and how each approaches these concepts, including a sample case study.

RESULTS

Each network approaches external validity differently. As its target population is US citizens and it includes only US data, Sentinel primarily worries about lack of external validity by not including some segments of the population. The fact that CNODES includes Canadian, United States, and United Kingdom data forces them to seriously consider whether the United States and United Kingdom data will be transportable to Canadian citizens when they meta-analyze database-specific estimates. PCORnet, with its focus on study-specific cohorts and pragmatic trials, conducts more case-by-case explorations of external validity for each new analytic data set it generates.

CONCLUSIONS

There is no one-size-fits-all approach to external validity within distributed networks. With these networks and comparisons between their findings becoming a key part of pharmacoepidemiology, there is a need to adapt tools for improving external validity to the distributed network setting.