Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb 20;12(4):1690.
doi: 10.3390/jcm12041690.

Methods for the Inclusion of Real-World Evidence in a Rare Events Meta-Analysis of Randomized Controlled Trials

Minghong Yao  1   2   3 , Yuning Wang  1   2   3 , Fan Mei  1   2   3 , Kang Zou  1   2   3 , Ling Li  1   2   3 , Xin Sun  1   2   3
Affiliations

Methods for the Inclusion of Real-World Evidence in a Rare Events Meta-Analysis of Randomized Controlled Trials

Minghong Yao et al. J Clin Med. .

Abstract

Background: Many rare events meta-analyses of randomized controlled trials (RCTs) have lower statistical power, and real-world evidence (RWE) is becoming widely recognized as a valuable source of evidence. The purpose of this study is to investigate methods for including RWE in a rare events meta-analysis of RCTs and the impact on the level of uncertainty around the estimates.

Methods: Four methods for the inclusion of RWE in evidence synthesis were investigated by applying them to two previously published rare events meta-analyses: the naïve data synthesis (NDS), the design-adjusted synthesis (DAS), the use of RWE as prior information (RPI), and the three-level hierarchical models (THMs). We gauged the effect of the inclusion of RWE by varying the degree of confidence placed in RWE.

Results: This study showed that the inclusion of RWE in a rare events meta-analysis of RCTs could increase the precision of the estimates, but this depended on the method of inclusion and the level of confidence placed in RWE. NDS cannot consider the bias of RWE, and its results may be misleading. DAS resulted in stable estimates for the two examples, regardless of whether we placed high- or low-level confidence in RWE. The results of the RPI approach were sensitive to the confidence level placed in RWE. The THM was effective in allowing for accommodating differences between study types, while it had a conservative result compared with other methods.

Conclusion: The inclusion of RWE in a rare events meta-analysis of RCTs could increase the level of certainty of the estimates and enhance the decision-making process. DAS might be appropriate for inclusion of RWE in a rare event meta-analysis of RCTs, but further evaluation in different scenarios of empirical or simulation studies is still warranted.

Keywords: meta-analysis; randomized controlled trial; rare events; real-world evidence.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interest.

Similar articles

See all similar articles

Cited by

References

    1. Zabor E.C., Kaizer A.M., Hobbs B.P. Randomized Controlled Trials. Chest. 2020;158:S79–S87. doi: 10.1016/j.chest.2020.03.013. - DOI - PMC - PubMed
    1. Xu C., Li L., Lin L., Chu H., Thabane L., Zou K., Sun X. Exclusion of studies with no events in both arms in meta-analysis impacted the conclusions. J. Clin. Epidemiol. 2020;123:91–99. doi: 10.1016/j.jclinepi.2020.03.020. - DOI - PubMed
    1. Hodkinson A., Kontopantelis E. Applications of simple and accessible methods for meta-analysis involving rare events: A simulation study. Stat. Methods Med. Res. 2021;30:1589–1608. doi: 10.1177/09622802211022385. - DOI - PMC - PubMed
    1. Jia P., Lin L., Kwong J., Xu C. Many meta-analyses of rare events in the Cochrane Database of Systematic Reviews were underpowered. J. Clin. Epidemiol. 2020;131:113–122. doi: 10.1016/j.jclinepi.2020.11.017. - DOI - PubMed
    1. Sherman R.E., Anderson S.A., Dal Pan G.J., Gray G.W., Gross T., Hunter N.L., LaVange L., Marinac-Dabic D., Marks P.W., Robb M.A., et al. Real-World Evidence—What Is It and What Can It Tell Us? N. Engl. J. Med. 2016;375:2293–2297. doi: 10.1056/NEJMsb1609216. - DOI - PubMed

LinkOut - more resources