Table 2.

Possible endpoints for trials in COVID-19, corresponding target population, categorization of whether the endpoint is clinically meaningful, captures the diverse nature of disease, easy to measure, and reproducible.

Endpoint	Example	Population	Clinically meaningful	Multiple disease states	Time element	Easily measurable	Reproducibility	Additional comments
Binary outcomes Mortality	Death by 28	Moderate Severe Critical	+	○	○	+	+	+ Most relevant in severe/critical disease − May miss other meaningful improvements in patient status − Requires large sample size
Recovery(discharge, discharge-eligible)	Recovered by day 28	Moderate Severe	+	○	○	+	○	− May require long observation times in higher severity populations − Deaths require special consideration
Respiratory failure	ECMO or mechanical ventilation	Moderate Severe	+	○	○	+	○	− Depends on resources − Deaths require special consideration
Hospitalization	Admission within 28 days	Mild	+	−	○	+	○	− Depends on resources − Does not capture improvement − Deaths require special consideration
ICU admission	Admission within 28 days	Moderate	+	−	○	+	○	− Depends on resources − Does not capture improvement − Deaths require special consideration
Ordinal outcomes Ordinal disease severity scale	WHO scale at a fixed day	Moderate Severe	+	+	−	○	○	− Depends on resources − Defining clinical benefit less straightforward
Time-to-event outcomes Time to recovery	Time to discharge or eligible for discharge	Moderate Severe	+	○	+	+	○	− Depends on resources − Potential for “relapse” (sustained improvement removes this concern) − Deaths require special consideration
Time to 1- or 2-point improvement in ordinal scale1	Time to 2-point improvement }in WHO ordinal scale	Moderate Severe Critical	+	○	+	○	+	− Changes in categories must be meaningful and should be considered equally important − Potential for “relapse” (sustained improvement removes this concern)
Time to intubation or death		Moderate Severe	+	-	+	+	○
Continuous outcomes National Early Warning Score (NEWS score)		Moderate Severe	○	+	○	−	+	+ Familiar measure − Not disease-specific and hence not as sensitive to certain aspects of COVID − Deaths need special consideration
Viral load/viral clearance		Mild Moderate Severe Critical	−	○	○	−	−	− Difficult to reliably measure − Relation to clinical outcomes not well established − Deaths need special consideration
Oxygen, SpO2/FiO2 or paO2/FiO2	Daily SpO2/FiO2 until discharge, death or 28 days	Mild Moderate	○	○	○	−	+	− Relation to clinical outcomes not well established − Modified by oxygen supplementation − SpO2/FiO2 not well-validated − paO2/FiO2 only broadly available for ICU patients + Deaths need special consideration
Duration of a specific ordinal state	Hopitalization days; mechanical ventilation days	Severe Critical	○	−	○	+	○	+ Captures dimension meaningful to health system + Depends on the resources available + Deaths need special consideration
FLU-PRO	Change from baseline to day 14	Mild Moderate Critical	○	+	−	○	○	+ Captures aspects important to patients − Deaths need special consideration − Not validated for COVID-19
SOFA score	Change from baseline to day 14	Severe Critical	○	+	−	○	+	+ Captures disease severity and incorporates most relevant organ systems − Familiar for ICU setting − Not validated for COVID-19 and not disease-specific − Deaths need special consideration

COVID-19: coronavirus-induced disease; ECMO: extracorporeal membrane oxygenation; WHO: World Health Organization; ICU: intensive care unit; FLU-PRO: InFLUenza patient-reported outcome; SOFA score: sequential organ failure assessment score.

“ + “ indicates good performance; “−“ indicates poor performance on this characteristic; neutral is denoted by “○.”