Citation

Katz IR. JAMA Netw. Open 2019; 2(10): e1913284.

Affiliation

Office of Mental Health and Suicide Prevention, Department of Veterans Affairs, Philadelphia, Pennsylvania.

Copyright

(Copyright © 2019, American Medical Association)

DOI

10.1001/jamanetworkopen.2019.13284

PMID

31617919

Abstract

Mamdani et al1 reported on a nested case-control study using real-world data that finds that patients receiving angiotensin receptor blockers (ARBs) are associated with a greater risk of suicide than those receiving angiotensin-converting enzyme inhibitors (ACEIs). This is the sort of finding—the identification of a serious but rare adverse drug effect—that could only come from real-world data. The authors note that their conclusions should be viewed as preliminary, with a need for confirmation through additional research, at least in part because there may be differences in how the medications are used between geographic areas or health systems. Overall, the findings are important, but they require replication based on data from other populations and a synthesis of the evidence. The problem is that our current system provides few incentives or rewards for replication.

There is a body of evidence indicating that angiotensin has a role in modulating brain activity, behavior, and, possibly, mood,2 and Mamdani et al1 suggest a plausible mechanism for the differential effects of ACEIs and ARBs. However, they acknowledge that there is a need for additional neurobiological research in this area. There is also a need for additional behavioral research. Mamdani et al1 did not report on analyses designed to identify symptoms or deficits that could mediate the observed effects. This would be necessary before developing strategies for monitoring patients receiving ARBs and for early identification of those at risk. However, while additional information about brain and behavioral mechanisms could strengthen the reported findings, validated evidence about adverse drug effects from studies based on real-world data should be considered in practice and policy, even when no mechanisms are apparent.

A number of ongoing developments are increasing the capacity for research using real-world data. These include the implementation of the 21st Century Cures Act by the US Food and Drug Administration (FDA) and the FDA’s increasing use of the Sentinel3 system as part of the 21st Century Cures Act’s mandate to include real-world evidence in regulatory decision-making. Other ongoing developments include the increasing availability of data from electronic medical records from large health systems and advances in data mining and related analytical methods. With these increases in capacity, there have been discussions regarding the strengths and limitations of ...

Language: en