Open Access

Response to: Understanding the null hypothesis (H0) in non-inferiority trials

Critical Care201721:201

https://doi.org/10.1186/s13054-017-1790-2

Published: 4 August 2017

The original article was published in Critical Care 2017 21:101

We thank Dr. Mallat for their interest in our study of stepwise lactate kinetics-oriented hemodynamic therapy and for putting forward a statistical problem [1]. Central venous oxygen saturation (ScvO2)-targeted therapy was recommended by the Surviving Sepsis Campaign (SCC) guidelines in 2012 [2] and we initially envisaged that the stepwise lactate kinetics strategy was, at least, not inferior to the ScvO2 target strategy. Therefore, the design of non-inferiority analysis was adopted at the beginning of the trial.

We rechecked and recalculated the data by non-inferiority and superiority test. The lactate kinetics group mortality rate (P1) was 18.3% and the Scvo2 group mortality rate (P2) was 27.9%. The standard error for the mortality difference between the two groups was 0.0441, and thus the mortality difference was –0.0944 (95% confidence interval –0.1809 to –0.0080). The upper limit of the interval is less than 0, and thus the superiority conclusion is established. At this point, regardless of the non-inferior value (0.15 or 0.10), non-inferior conclusions must be established.

Additionally, the non-inferiority threshold of 10% is indeed more reasonable according to a previous study [3].Therefore, regardless of whether the non-inferiority threshold is set at 10% or 15%, no effect on the final conclusion was seen in this study.

Last, but not the least, the latest sepsis guidelines released by the SCC in 2016 have weakened early goal-directed therapy (EGDT) and highlighted the importance of normalization of lactate [4], which also supports the conclusion we draw that stepwise lactate kinetics-oriented hemodynamic therapy can reduce mortality in patients with sepsis-associated hyperlactatemia compared with ScvO2-oriented therapy.

Notes

Abbreviations

EGDT: 

Early goal-directed therapy

SCC: 

Surviving Sepsis Campaign

ScvO2: 

Central venous oxygen saturation

Declarations

Acknowledgements

We thank Prof. Guangliang Shan and Dr. Biao Zhang from the Department of Epidemiology and Biostatistics, Institute of Basic Medicine Sciences, Chinese Academy of Medical Sciences (CAMS) & School of Basic Medicine, Peking Union Medical College for helping us to check and perform the statistical analysis.

Funding

Not applicable.

Availability of data and materials

Not applicable.

Authors’ contributions

XZ, LS, and DL drafted the manuscript. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences

References

  1. Mallat J. Understanding the null hypothesis (H0) in non-inferiority trials. Crit Care. 2017;21(1):101.View ArticlePubMedPubMed CentralGoogle Scholar
  2. Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med. 2013;39(2):165–228.View ArticlePubMedGoogle Scholar
  3. Jones AE, Shapiro NI, Trzeciak S, Arnold RC, Claremont HA, Kline JA. Lactate clearance vs central venous oxygen saturation as goals of early sepsis therapy: a randomized clinical trial. JAMA. 2010;303(8):739–46.View ArticlePubMedPubMed CentralGoogle Scholar
  4. Rhodes A, Evans LE, Alhazzani W, Levy MM, Antonelli M, Ferrer R, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med. 2017;43(3):304–77.View ArticlePubMedGoogle Scholar

Copyright

© The Author(s). 2017

Advertisement