Asthma clinical research lacks adequate outcomes standardization. As a result, our ability to examine and compare outcomes across clinical trials and clinical studies, interpret evaluations of new and available therapeutic modalities for this disease at a scale larger than a single trial, and pool data for observational studies (eg, genetics, genomics, pharmacoeconomics) is impaired.4
Several National Institutes of Health (NIH) institutes that support asthma research (the National Heart, Lung, and Blood Institute; the National Institute of Allergy and Infectious Diseases; the National Institute of Environmental Health Sciences; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development), as well as the Agency for Healthcare Research and Quality, have agreed to an effort for outcomes standardization. This effort aims at (1) establishing standard definitions and data collection methodologies for validated outcome measures in asthma clinical research with the goal of enabling comparisons across asthma research studies and clinical trials and (2) identifying promising outcome measures for asthma clinical research that require further development. In the context of this effort, 7 expert subcommittees were established to propose and define outcomes under 3 categories—core, supplemental, and emerging:
- Core outcomes are identified as a selective set of asthma outcomes to be considered by participating NIH institutes and other federal agencies as requirements for institute/agency-initiated funding of clinical trials and large observational studies in asthma.
- Supplemental outcomes are asthma outcomes for which standard definitions can or have been developed, methods for measurement can be specified, and validity has been proved but whose inclusion in funded clinical asthma research will be optional.
- Emerging outcomes are asthma outcomes that have the potential to (1) expand and/or improve current aspects of disease monitoring and (2) improve translation of basic and animal model–based asthma research into clinical research. Emerging outcomes may be new or may have been previously used in asthma clinical research, but they are not yet standardized and require further development and validation.
Each subcommittee used the recently published American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement: Asthma Control and Exacerbations—Standardizing Endpoints for Clinical Asthma Trials and Clinical Practice5
(hereafter referred to as the ATS/ERS Statement) as a starting point and updated, expanded, or modified its recommendations as the subcommittee deemed appropriate. Each subcommittee produced a report that was discussed, modified, and adopted by the Asthma Outcomes Workshop that took place in Bethesda, Md, on March 15 and 16, 2010. The reports were revised accordingly and finalized in September 2011. The recommendations of the workshop participants in regard to asthma biomarkers are presented in this article and summarized in , 1–3
, and III.
Recommendations for classifying asthma biomarker outcome measures for NIH-initiated clinical research for adults and children
Methods for measuring and reporting core and supplemental biomarker outcomes
The measurement of biomarkers has been incorporated within clinical studies of asthma to characterize the participant population and to try to associate the disease process with environmental effects and therapeutic interventions.
This summary highlights the current knowledge regarding biomarkers deemed applicable as core measures, specifically the multiallergen screen to define atopy, and supplemental biomarkers, which include measurements of sputum eosinophils, IgE, complete blood count (CBC), fractional exhaled nitric oxide (Feno), and urinary leukotrienes. In addition, several biomarkers are considered emerging measures, such as imaging and cortisol. Future studies will be required to further validate and characterize their roles as outcome measures. We also discuss the issue of proper storage of biologic samples to allow future analyses.
The conclusions of the Asthma Biomarkers Subcommittee extend those included in the ATS/ERS Statement by considering additional publications available since that report and by focusing our comments on the role of biomarkers in clinical research.5
There are no essential disagreements with the ATS/ERS Statement.