Stratification and Staging
Critical illness has traditionally been defined by syndromes – Acute Respiratory Distress Syndrome, sepsis, Multiple Organ Dysfunction Syndrome. While these reflect a clinical phenotype of critical illness, they do not correspond well to underlying biologic or pathologic mechanisms, and so have proven inadequate to inform diagnostic and, therapeutic decision-making. Unresolved biologic heterogeneity has been a recurring factor in our failure to develop and use effective biologic therapies, or even to use those we have most effectively.
Heterogeneity is an intrinsic element in other diseases such as cancer or heart disease. Advances in these disciplines has come through a better understanding of natural history and the development of better taxonomic classifications that identify sub-populations of patients who are more likely to respond to particular treatment strategies.
InFACT has been promoting a collaboration amongst trialists, as well as amongst investigators with an interest in large scale “omics” technologies and those with expertise in the aggregation and interpretation of large data sets with a view to rethinking how we classify acutely ill patients to better match biologic derangements to available treatments.
This is an ambitious project whose time frame is measured in decades, and whose success depends on finding common ground amongst a scientifically diverse group of researchers. Yet there is an extraordinary sense of willingness to explore the potential of such a collaboration. The potential projects to move this program forward include:
Developing a common taxonomy to describe the process
Standardizing sample collection and data annotation
Optimizing and harmonizing data platforms
Sharing samples and data, and developing agreements for doing so
Hosting colloquia and symposia
Developing large collaborative funding applications
Developing and testing candidate models
Encouraging trialists to collect samples to use the RCT as a platform for study
Secondary analyses of completed clinical trials to look for signals of differential treatment responsiveness
Benjamin Tang from Australia has drafted an initial overview of the project. We have had discussions at a variety of meetings in Toronto, San Francisco, Bangkok, and Paris, and are working to develop an organizational structure and research program to move the initiative forward.