Recommendations for the collection and annotation of biosamples for analysis of biomarkers in neurofibromatosis and schwannomatosis clinical trials

Abstract

Introduction: Neurofibromatosis 1 and schwannomatosis are characterized by potential lifelong morbidity and life-threatening complications. To date, however, diagnostic and predictive biomarkers are an unmet need in this patient population. The inclusion of biomarker discovery correlatives in neurofibromatosis 1/schwannomatosis clinical trials enables study of low-incidence disease. The implementation of a common data model would further enhance biomarker discovery by enabling effective concatenation of data from multiple studies.

Methods: The Response Evaluation in Neurofibromatosis and Schwannomatosis biomarker working group reviewed published data on emerging trends in neurofibromatosis 1 and schwannomatosis biomarker research and developed recommendations in a series of consensus meetings.

Results: Liquid biopsy has emerged as a promising assay for neurofibromatosis 1/schwannomatosis biomarker discovery and validation. In addition, we review recommendations for a range of biomarkers in clinical trials, neurofibromatosis 1/schwannomatosis-specific data annotations, and common data models for data integration.

Conclusion: These Response Evaluation in Neurofibromatosis and Schwannomatosis consensus guidelines are intended to provide best practices for the inclusion of biomarker studies in neurofibromatosis 1/schwannomatosis clinical trials, data, and sample annotation and to lay a framework for data harmonization and concatenation between trials.

Keywords: Biomarker; cell-free DNA; consensus guidelines; cytokines; liquid biopsy; neurofibromatosis; open science; schwannomatosis.

Figure 1.

Incorporation of molecular biomarkers in NF1/SWN clinical trials. Exploratory correlatives with tissue and circulating biomarkers in interventional trials, windows of opportunity trials, and natural history studies hold promise for enhancing diagnosis, prognostication, and treatment stratification of patients with NF1/SWN.

Figure 2.

Common data models and annotation ontology enables powered biomarker discovery and validation through the integration of multi-modal data from multiple studies and institutions. To power biomarker discovery in rare diseases like NF1 and SWN, standardized data collection, annotation, and processing must be widely adopted. This would enable data concatenation and harmonization. Importantly, resultant data, including raw molecular data, should be publicly available and disseminated through data repositories.