We aim to select candidate interventions to be tested in this trial, either in all or a subset of regions. The goal is to develop explicit terms of reference and methodology for the identification and prioritisation of candidate interventions for study. We will refer to major evidence-based guidelines and potential novel interventions relevant to CAP to select candidates. Each candidate intervention will be assessed on the following criteria:
- level of existing evidence;
- variability in current adoption into clinical practice including variation within and between clinical settings (plausible equipoise);
- rigorous value of information (VOI) analyses.
Most of Task 1 will be spent performing VOI analyses focused on determining both the degree of uncertainty surrounding the role of a given intervention and the value associated with reducing that uncertainty in a clinical trial. This approach will return the net benefit of testing certain candidate interventions against the potential losses from testing alternative interventions. Using results from the above analyses and trial feasibility, we will select the top candidate interventions from among 3 categories. Treatment of patients with CAP can be divided into three main treatment “packages”; 1) Bug package (aimed at the eradication of the infectious cause); 2) adjunctive package (aimed at the prevention of complications); and 3) ventilation package (aimed at optimizing support for failure of the respiratory system). Each selected intervention will fall into one of these three packages. Examples of candidate interventions to be considered in the VOI analysis are steroids, statins, fibrates, N-acetyl cysteine, resveratrol, nebulised heparin, glitazones, aspirin, COX-2 inhibitors, ACE inhibitors, macrolides, vitamin D and IV IgG. We will also consider interventions with a high level of evidence and adoption as candidate intervention. Within each package, the selected interventions will be compared to each other, but not to the interventions of the other packages.