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Fig. 1 | Critical Care

Fig. 1

From: Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study

Fig. 1

a Net benefit curves of three clinical trial enrollment strategies: enrolling all sepsis patients (black line), enrolling patients with septic shock (blue line), and enrolling sTNFR1 positive patients (red line). The x-axis represents the threshold probability, which is the probability of mortality that a hypothetical trial would require for enrollment. The y-axis is the net benefit, which represents the tradeoff between true positives and false positives, and is calculated as (true positives/n) − (false positive/n) × (pt/1 − pt), where pt is the threshold probability. The net benefit varies with the threshold probability since it reflects the relative harms of missing non-survivors (false negatives) and enrolling too many survivors (false positives). We focused on threshold probabilities between 15 and 50%, because enrichment is unnecessary at low thresholds given baseline mortality, and we reasoned that patients with > 50% mortality risk may be excluded from trials because they may be less likely to respond to therapy. Net benefit curves are interpreted vertically; at each threshold probability, the strategy with the highest net benefit is the optimal strategy for enriching a trial with high-risk subjects. For example, if a trial sought to enroll patients with at least 35% mortality risk (dotted vertical line), enrolling only sTNFR1-positive patients is the optimal strategy. b Intervention curves comparing enrolling all sepsis patients (reference, not shown), enrolling patients with septic shock (blue line), and enrolling sTNFR1 positive patients (red line). Intervention curves are an alternative representation of net benefit and are also interpreted vertically. The y-axis represents the number of survivors that avoid the intervention, which in this case is enrollment and exposure to unproven therapy. At a threshold probability of 35%, enrolling sTNFR1-positive patients would lead to a greater reduction in the number of survivors unnecessarily exposed compared to enrolling patients with septic shock

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