
==== Front
JACC CardioOncol
JACC CardioOncol
JACC: CardioOncology
2666-0873
Elsevier

S2666-0873(24)00211-4
10.1016/j.jaccao.2024.05.014
Letters
To the Editor
Reply
Assessing the Certainty of Evidence on Efficacy and Safety of Anticoagulants for Cancer-Associated Thrombosis
Fujisaki Tomohiro MD
Buckley Conor MD
Sueta Daisuke MD, PhD
Yamamoto Eiichiro MD, PhD eyamamo@kumamoto-u.ac.jp
∗
Tsujita Kenichi MD, PhD
∗ Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan eyamamo@kumamoto-u.ac.jp
02 7 2024
8 2024
02 7 2024
6 4 624624
© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.
2024

https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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pmcWe thank Dr Khan and colleagues for their interest in our study.1 The authors suggested a more detailed approach to rate the quality of treatment effect estimates from network meta-analysis (NMA), specifically through the use of the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) Working Group approach.2

The GRADE approach consists of 4 steps: 1) present direct and indirect treatment estimates; 2) rate the quality of each direct and indirect effect estimate; 3) present the NMA estimate; and 4) rate the quality of each NMA effect estimate. Although the GRADE approach was not used in our study, we included forest plots demonstrating direct, indirect, and NMA estimates to aid readers in understanding the reliability of effect estimates.

In our analysis (eg, major bleeding), only indirect estimates were available for most results, with GRADE certainty being moderate or high for these indirect estimates as Dr Khan and colleagues outlined in their letter. The GRADE Working Group approach indicates that the quality rating of the indirect comparison also represents the quality of the NMA when only indirect evidence is available.2 If this approach was strictly applied to our study, the consistently moderate to high GRADE certainty of the indirect comparisons would suggest that the associated NMA GRADE certainty would be unlikely to be “very low” as indicated by Dr Khan and colleagues. This disagreement may have arisen during the interpretation of the more subjective aspects of the GRADE approach as well as the known low inter-rater agreement associated with these methods. However, we acknowledge that the GRADE approach can be useful for rating quality.

In terms of the treatment ranking in our NMA, the treatment ranking method was used only as a supplemental analysis to support the main analysis by showing concordance. Even without the treatment ranking analyses, we could have drawn the same principal findings in our study. We do agree that treatment rankings do not account for the certainty of the evidence; therefore, they should be used only as a supplementary tool.

We acknowledge that our study has several limitations, and the application of our results indeed requires understanding the quality of the evidence. The GRADE approach could be considered as an approach to assess the quality of the evidence, but the low inter-rater agreement of the methods should be noted. Our study synthesized limited but important evidence to guide clinicians, and further studies are needed to directly compare various direct oral anticoagulants in patients with venous thromboembolism and active cancer.

Funding Support and Author Disclosures

This study was supported by Grants-in-Aid for Scientific Research (#20K17087) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funder had no role in this study. Dr Tsujita has received honoraria from Bayer Yakuhin and Daiichi-Sankyo; and has received grants from Bayer Yakuhin, Boehringer Ingelheim Japan, and Daiichi-Sankyo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
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References

1 Fujisaki T. Sueta D. Yamamoto E. Comparing anticoagulation strategies for venous thromboembolism associated with active cancer: a systematic review and meta-analysis J Am Coll Cardiol CardioOnc 6 1 2024 99 113
2 Puhan M.A. Schünemann H.J. Murad M.H. A GRADE Working Group approach for rating the quality of treatment effect estimates from network meta-analysis BMJ 349 2014 g5630
