Table 2

Decomposition of effects: OR for the natural direct effect (NDE), the natural indirect effect (NIE) and the total causal effect (TCE)

	Between-group effect not mediated via CRP	Between-group effect mediated via CRP	Total effect
	OR_NDE	OR_NIE	OR_TCE
Improvement at 14 days	1.38*	2.27	3.14
Survival at 30 days	1.16	1.60	1.87
Survival at 90 days	1.16	1.49	1.73

Two types of contrasts can be distinguished: contrasts not mediated by CRP response and contrasts mediated by CRP response. Contrasts not mediated by CRP response refer to ‘natural’ prognostic differences between period 1 and period 2 and may include differences existing already at baseline (measured and unmeasured) or differences occurring during follow-up (eg, differences in ventilatory support, or differences in antithrombotic treatment or unwarranted effects due to bacterial superinfection). Contrasts mediated by CRP response include differences specifically due to immunosuppressive therapy under the assumption that these cause suppression of inflammation (as assessed by an 80% CRP response).
*ORs refer to the contrast in outcome between period 2 and period 1. OR <1 indicates less effect on the outcome in period 2 than in period 1; OR >1 indicates more effect in period 2 than in period 1.
CRP, C reactive protein.