A Research Agenda for Precision Medicine in Sepsis and Acute Respiratory Distress Syndrome: An Official American Thoracic Society Research Statement

Faraaz Ali Shah, Nuala J Meyer, Derek C Angus, Rana Awdish, Élie Azoulay, Carolyn S Calfee, Gilles Clermont, Anthony C Gordon, Arthur Kwizera, Aleksandra Leligdowicz, John C Marshall, Carmen Mikacenic, Pratik Sinha, Balasubramanian Venkatesh, Hector R Wong, Fernando G Zampieri, Sachin Yende, Faraaz Ali Shah, Nuala J Meyer, Derek C Angus, Rana Awdish, Élie Azoulay, Carolyn S Calfee, Gilles Clermont, Anthony C Gordon, Arthur Kwizera, Aleksandra Leligdowicz, John C Marshall, Carmen Mikacenic, Pratik Sinha, Balasubramanian Venkatesh, Hector R Wong, Fernando G Zampieri, Sachin Yende

Abstract

Background: Precision medicine focuses on the identification of therapeutic strategies that are effective for a group of patients based on similar unifying characteristics. The recent success of precision medicine in non-critical care settings has resulted from the confluence of large clinical and biospecimen repositories, innovative bioinformatics, and novel trial designs. Similar advances for precision medicine in sepsis and in the acute respiratory distress syndrome (ARDS) are possible but will require further investigation and significant investment in infrastructure. Methods: This project was funded by the American Thoracic Society Board of Directors. A multidisciplinary and diverse working group reviewed the available literature, established a conceptual framework, and iteratively developed recommendations for the Precision Medicine Research Agenda for Sepsis and ARDS. Results: The following six priority recommendations were developed by the working group: 1) the creation of large richly phenotyped and harmonized knowledge networks of clinical, imaging, and multianalyte molecular data for sepsis and ARDS; 2) the implementation of novel trial designs, including adaptive designs, and embedding trial procedures in the electronic health record; 3) continued innovation in the data science and engineering methods required to identify heterogeneity of treatment effect; 4) further development of the tools necessary for the real-time application of precision medicine approaches; 5) work to ensure that precision medicine strategies are applicable and available to a broad range of patients varying across differing racial, ethnic, socioeconomic, and demographic groups; and 6) the securement and maintenance of adequate and sustainable funding for precision medicine efforts. Conclusions: Precision medicine approaches that incorporate variability in genomic, biologic, and environmental factors may provide a path forward for better individualizing the delivery of therapies and improving care for patients with sepsis and ARDS.

Keywords: acute respiratory distress syndrome; precision medicine; sepsis.

Figures

Figure 1.
Figure 1.
Conceptual model of the path forward for precision medicine in sepsis and the acute respiratory distress syndrome. EHR = electronic health record.

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