This report summarizes the findings of a workshop convened by the Division of Lung Diseases of the National Heart, Lung, and Blood Institute on August 5-6, 2009. The goal of the workshop was to assess the current state of clinical research in acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS), identify research needs, and develop recommendations for clinical research in the near future.
Data on mortality attributable to ALI are conflicting, but both longitudinal observations at single institutions and the experience of the NHLBI ARDS Clinical Trials Network suggest a substantial decline over the past two decades. Studies from the Network permit comparison of mortalities in patients of similar disease severity and source, and in these studies mortality has fallen from 40% in studies conducted in the late 1990’s (ARMA) to the low 20s in the most recent reports (FACTT). Consequently, clinical trials powered to detect differences in mortality may require ever increasing numbers of patients. The panel was charged to examine whether novel investigational strategies might allow studies enrolling smaller numbers of patients, and to consider other types of clinical research that would advance the science and treatment of ALI/ARDS. The group included pulmonary critical care and cardiovascular clinician scientists experienced in the design and conduct of clinical research as well as statistical and genetic experts.
Panelists were asked to consider issues in the following areas:
- Current operational definitions of ALI and ARDS;
- Usefulness of biomarkers and genetic markers in studies of ALI;
- Significance of non-ALI patients without chronic lung disease who are in the ICU and receiving mechanical ventilation for > 72 h.
- Importance of quality of life studies of ALI survivors;
- Clinical study endpoints;
- Feasibility of ALI prevention trials;
- Value of Phase II studies;
- Trial design
Published in the American Journal of Respiratory and Critical Care Medicine Vol 181. pp. 1121-1127, (2010)
Prioritized Recommendations and Conclusions
- Highest priority is suggested for large phase II/III studies primarily designed to optimize current interventions. These studies will also permit continued exploration of biomarkers and genetic factors, to identify subpopulations, predict outcome, facilitate diagnosis, describe pharmacogenomic effects that influence response to therapy, and provide insight into mechanisms of lung injury. Collection of appropriate samples, including DNA, from study participants is essential. Study of the impact of interventions on cognitive function and quality of life are of high value, and should be a fundamental part of phase III trials.
- Phase II or phase II/III studies should continue, aiming to identify and test new interventions and provide data that could be used to justify larger efficacy studies.
- Strategies to perform ALI prevention trials should be developed. These may involve collaboration with other clinical groups (e.g., emergency department) and certainly will be facilitated by new informatics technologies such as the electronic medical record.
- Observational studies of patients with and without chronic lung disease but who are undergoing mechanical ventilation for longer than 72 hours are recommended. Such studies may improve understanding of how critical care resources are being spent, facilitate process of care studies and effectiveness research, allow assessment of the impact of premorbid conditions on outcome, and suggest outcome measures that are alternatives to mortality.
- Roger Spragg, M.D., University of California, San Diego
- John H. Alexander, M.D., MHS, FACC, Duke University Medical Center
- Gordon R. Bernard, M.D, Vanderbilt University Medical Center*
- William Checkley, M.D., Ph.D., Johns Hopkins University
- Nancy Cox, Ph.D., University Of Chicago
- J. Randall Curtis, M.D., Harborview Medical Center
- Ognjen Gajic, M.D., Mayo Clinic
- Gordon H. Guyatt, M.D. MSc., FRCP McMaster University
- Jessee Hall, M.D., University of Chicago Medical Center*
- Elliot Israel, M.D, Brigham and Women’s Hospital*
- Manu Jain, M.D., MSCI, Northwestern University
- Dale Needham, M.D., Ph.D., Johns Hopkins University
- Adrienne Randolph, M.D, Boston Children’s Hospital
- David Reboussin, Ph.D., Wake Forest University School of Medicine
- Gordon Rubenfeld, M.D., University of Toronto
- David Schoenfeld, Ph.D., Harvard School of Public Health*
- B. Taylor Thompson, M.D., Massachusetts General Hospital*
- Lorraine Ware, M.D., Vanderbilt University Medical Center
- Duncan Young, M.D., Oxford Radcliffe Hospitals NHS Trust
- Andrea L Harabin, Ph.D., Division of Lung Diseases
Last Updated June 2011