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Response to: ‘Correspondence on ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19- associated cytokine storm syndrome: results of the CHIC study’’ by Klopfenstein et al
  1. Robert BM Landewé1,2,
  2. Sofia Ramiro1,3,
  3. Rémy L M Mostard4
  1. 1 Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
  2. 2 Amsterdam Rheumatology Center, AMC, Amsterdam, The Netherlands
  3. 3 Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  4. 4 Department of Pulmonology, Zuyderland Medical Centre Heerlen, Heerlen, The Netherlands
  1. Correspondence to Professor Robert BM Landewé, Amsterdam Rheumatology Center, AMC, 1105 AZ Amsterdam, Netherlands; landewe{at}

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In rheumatology and beyond, clinical trial researchers often interpret observed treatment contrasts (between two trial arms) as if these contrasts are constant across the entire spectrum of disease severity. While understandable, researchers, regulators and society usually aim at finding one effective treatment for the whole disease, a constant effect interpretation is a simplification of the truth. Often, effective treatments have relatively most effect when applied in the sickest. Benefit may be less impressive when applied in those with milder disease: effect modification or (statistical) interaction. Klopfenstein et al touch on this rather ubiquitous but often ignored phenomenon, by demonstrating that the treatment contrast of tocilizumab versus control in trials with patients with COVID-19 is not constant but …

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  • Handling editor Josef S Smolen

  • Contributors RBML drafted the response. All authors reviewed and approved the final response.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Commissioned; internally peer reviewed.

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