Assessment criteria

Candidate interventions are discussed and assessed by the platform intervention selection committee based on the criteria set out below.

Domain 1 - Evidence base

1.1     Sub-phenotype

• Is there evidence of a differential response to the proposed intervention among sub-phenotypes of ARDS?

Levels:

• Pre-clinical
• Observational
• Re-analysis of a randomised controlled trial

Grades: Strong, moderate, or weak

• Are these sub-phenotypes consistent with the PANTHER platforms approach to stratification?

• Is there sufficient evidence to suggest the mechanism by which the intervention exerts benefit and is further investigation of this mechanism tractable within the platform?

1.2     ARDS

• Is there evidence of efficacy in ARDS?

Levels:

• Pre-clinical
• Observational
• Randomised controlled trial

Grades: Strong, moderate, or weak

1.3     COVID-19 ARDS

• Is there evidence of efficacy in COVID-19 ARDS?

Levels:

• Pre-clinical
• Observational
• Randomised controlled trial

Grades: Strong, moderate, or weak

1.4     Related condition

• Is there evidence of efficacy in an inflammatory condition related to ARDS?

Levels:

• Pre-clinical
• Observational
• Randomised controlled trial

Grades: Strong, moderate, or weak

• Does sufficient mechanistic data exist to show that similar effects could reasonably be expected in an ARDS sub-phenotype?

Domain 2 - Safety and pharmacology data

2.1     Safety

• At what phase of development is the intervention?

• Does the intervention have important cautions or contraindications?

• Does the intervention have important interactions?

• What are the common or important side-effects?

• Is a reversal agent available?

2.2     PK/PD data

• Is robust PK/PD data available?

• If so, are data specific to a critical illness population? Do these data extend to patients in receipt of RRT and/or ECMO?

Domain 3 - Feasibility

3.1     Suitable formulation

• Is there a formulation of the intervention that is suitable for administration to critically ill and mechanically ventilated patients?

• Does the proposed intervention require special preparation, storage or handling?

• What is the anticipated duration of the intervention and what is the dosing schedule?

3.2     Scalable to trial

• Is the supply of the intervention scalable to an international, multi-centre study?

• Can the supply of the intervention be guaranteed for the anticipated duration of recruitment?

• For repurposed interventions, what is the prevalence of use in the population that the trial seeks to include?

• Does the intervention require therapeutic drug monitoring?

• Does the intervention require the use of an additional biomarker to guide administration?

3.3     Ongoing or planned studies

• Are there ongoing or planned studies of the intervention in the same or a similar population? If so, would inclusion of the intervention in PANTHER be likely to offer novel or superior information?