Mycobacterium avium complex Core Outcomes Research (MACCOR)

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PROJECT SUMMARY/ABSTRACT Pulmonary Mycobacterium avium complex (MAC) is a chronic infection and airway inflammatory disease with systemic manifestations affecting multiple aspects of our patients' lives. Similar to other chronic inflammatory diseases, such as rheumatoid arthritis, the impact of pulmonary MAC disease (pMACd) varies between individuals with regards to presentation, course and response to therapy. Lifelong management is often required, as recurrence is common. The treatment burden is high with patients typically taking 3-5 antibiotics for 18-24 months. In clinical practice, sputum culture results, radiographic findings, and symptoms drive treatment decisions. While conversion of sputum culture to negative implies microbiologic success, it does not imply infection eradication and it is inadequate to assess the full impact of this disease on our patients' lives. Importantly, the US Food and Drug Administration does not consider culture conversion an adequate endpoint in therapeutic trials for pMACd. As this disease has become recognized to be increasing in incidence and its tremendous unmet need for antibiotics highlighted, a pipeline of new therapeutics for this orphan disease has recently materialized. However randomized clinical trials are currently stymied by a lack of validated outcome measures. Objective measures of function, health-related quality of life, radiographic changes and biomarkers are needed as clinical outcomes. Further, the heterogeneity of this disease's natural history is reflected by the fact that culture, radiography, and symptomatology often do not change together. A combined outcome measure along several domains (symptoms, radiologic, etc.) would better capture disease activity and could be useful both clinically as well as in clinical trials of new therapeutics. Currently, there are no validated outcome measures in pMACd and potential outcomes are not measured consistently across all studies. In order to facilitate development of a future combined disease activity measure, this proposal aims to identify a set of core outcome domains and the best available instruments for a minimum core outcome measurement set that can be consistently collected across future clinical trials. First, we will identify a set of core outcome domains for pMACd essential to patients, caregivers, patient advocates, clinical experts, and researchers through an international consensus process using the Delphi methodology. Second, we will evaluate the impact of pulmonary MAC treatment on various available measurement instruments that represent the identified core outcome domains, by utilizing available clinical datasets. Third, we will identify a minimum core outcome measurement instrument set essential for future pMACd clinical trials through the international Delphi consensus process. This will enable comparisons between clinical trials and meta-analyses, both important in a rare disease such as pulmonary MAC. The results of this project will contribute significantly to an improvement in clinical care, future therapeutic trials and observational research, in addition to facilitating future development of a combined disease activity measure in pMACd.