{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:27:22Z","timestamp":1772166442032,"version":"3.50.1"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"DOI":"10.1186\/s13063-024-08679-5","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T04:53:18Z","timestamp":1734497598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Limitation of site-stratified cox regression analysis in survival data: a cautionary tale of the PANAMO phase III randomized, controlled study in critically ill COVID-19 patients"],"prefix":"10.1186","volume":"25","author":[{"given":"Christian E.","family":"Sandrock","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7881-7182","authenticated-orcid":false,"given":"Peter X. K.","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"8679_CR1","unstructured":"ICH Harmonized Tripartite Guideline: Structure and Content of Clinical Study Reports E3, https:\/\/database.ich.org\/sites\/default\/files\/E3_Guideline.pdf. Accessed 14 Aug, 2024."},{"key":"8679_CR2","unstructured":"ICH Harmonized Guideline Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice E6(R2), https:\/\/database.ich.org\/sites\/default\/files\/E6_R2_Addendum.pdf. Accessed 14 Aug, 2024."},{"key":"8679_CR3","unstructured":"ICH Harmonized Tripartite Guideline: Statistical Principles for Clinical Trials E9, https:\/\/database.ich.org\/sites\/default\/files\/E9_Guideline.pdf. Accessed 14 Aug, 2024."},{"key":"8679_CR4","unstructured":"Shreffler J, Huecker MR. Type I and type II errors and statistical power. 2023 Mar 13. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023."},{"key":"8679_CR5","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S0197-2456(00)00106-9","volume":"21","author":"MA Proschan","year":"2000","unstructured":"Proschan MA, Waclawiw MA. Practical guidelines for multiplicity adjustment in clinical trials. Control Clin Trials. 2000;21:527\u201339.","journal-title":"Control Clin Trials"},{"issue":"5","key":"8679_CR6","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1177\/1740774520941419","volume":"17","author":"RA Parker","year":"2020","unstructured":"Parker RA, Weir CJ. Non-adjustment in multiple testing in multi-arm trials of distinct treatments: rationale and justification. Clin Trials. 2020;17(5):562\u20136.","journal-title":"Clin Trials"},{"issue":"6","key":"8679_CR7","doi-asserted-by":"publisher","first-page":"1075","DOI":"10.5811\/westjem.2017.8.35985","volume":"18","author":"CE McCoy","year":"2017","unstructured":"McCoy CE. Understanding the intention-to-treat principle in randomized controlled trials. West J Emerg Med. 2017;18(6):1075\u20138.","journal-title":"West J Emerg Med"},{"issue":"1","key":"8679_CR8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/sim.1328","volume":"22","author":"A Phillips","year":"2003","unstructured":"Phillips A, Haudiquet V. ICH E9 guideline \u2018Statistical principles for clinical trials\u2019: a case study. Stat Med. 2003;22(1):1\u201311; discussion 13-17.","journal-title":"Stat Med."},{"issue":"12","key":"8679_CR9","doi-asserted-by":"publisher","first-page":"1137","DOI":"10.1016\/S2213-2600(22)00297-1","volume":"10","author":"APJ Vlaar","year":"2022","unstructured":"Vlaar APJ, Witzenrath M, van Paassen P, for the PANAMO study group, et al. Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Respir Med. 2022;10(12):1137\u201346.","journal-title":"Lancet Respir Med."},{"key":"8679_CR10","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1146\/annurev.immunol.23.021704.115835","volume":"23","author":"RF Guo","year":"2005","unstructured":"Guo RF, Ward PA. Role of C5a in inflammatory responses. Annu Rev Immunol. 2005;23:821\u201352.","journal-title":"Annu Rev Immunol"},{"key":"8679_CR11","unstructured":"Emergency Use Authorization (EUA) for Vilobelimab (IFX-1) Center for Drug Evaluation and Research (CDER) Review, https:\/\/www.fda.gov\/media\/167044\/download?attachment. Accessed 14 Aug, 2024."},{"key":"8679_CR12","unstructured":"Emergency Use Authorization of Gohibic, Letter of Authorization, https:\/\/www.fda.gov\/media\/166823\/download?attachment. Accessed 14 Aug. 2024."},{"issue":"4","key":"8679_CR13","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1007\/s12350-014-9908-2","volume":"21","author":"B George","year":"2014","unstructured":"George B, Seals S, Aban I. Survival analysis and regression models. J Nucl Cardiol. 2014;21(4):686\u201394.","journal-title":"J Nucl Cardiol"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08679-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-024-08679-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-024-08679-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T05:07:15Z","timestamp":1734498435000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-024-08679-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,18]]},"references-count":13,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["8679"],"URL":"https:\/\/doi.org\/10.1186\/s13063-024-08679-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-4014713\/v1","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,18]]},"assertion":[{"value":"4 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the institutional review boards or ethics committees for each site and conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki of 1975. The study protocol (Reference 9; appendix pp 39\u2013250) was approved by an institutional review board (Amsterdam UMC, Amsterdam, Netherlands; IRB 2020_067#B2020179, Study Title: A Pragmatic Adaptive Randomized Controlled Phase II\/III Multicenter Study of IFX-1 in Patients with Severe COVID-19 Pneumonia\u2014\u201cPANAMO\u201d). All patients or their legally authorized representatives provided written informed consent. In the Netherlands, Germany, and Russia, deferred consent procedures were allowed. Deferred consent involved randomization at investigators discretion according to pre-set criteria agreed on during ethical review of the protocol, followed by the request for patient\u2019s (deferred patient consent) or representative\u2019s (deferred proxy consent) informed consent during the study [Jansen TC, Kompanje EJO, Druml C, et al.: Deferred consent in emergency intensive care research: what if the patient dies early? Use the data or not? Intensive Care Med 2007; 33:894\u2013900].","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"PHKS has acted as a statistical consultant for InflaRx GmbH.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"822"}}