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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 …
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.