Alliance to Standardize Biomarker Discovery, Validation Process
The success rate in identifying and incorporating clinically meaningful biomarkers into practice is “dismal,” says the newly formed National Biomarker Development Alliance (NBDA). The alliance was announced in January with the goal of establishing an agreed upon comprehensive, evidence-based biomarker development process. These standards are urgently needed, the group says, to identify the high-quality biomarkers […]
The success rate in identifying and incorporating clinically meaningful biomarkers into practice is “dismal,” says the newly formed National Biomarker Development Alliance (NBDA). The alliance was announced in January with the goal of establishing an agreed upon comprehensive, evidence-based biomarker development process. These standards are urgently needed, the group says, to identify the high-quality biomarkers required to support personalized medicine. The group, established with assistance from the Research Collaboratory of Arizona State University, will be “disease agnostic” and will focus on developing standards including best practices, guidelines, and standard operating procedures; a national biomarker biorepository; a network to reproduce selected biomarker results; and a common biomarker database. The input of stakeholders nationally representing industry, academia, patient groups, and government is being sought. “Creating the standards and systems for successful biomarker development is complex but achievable through a new generation of networks of stakeholders that integrate knowledge to solve critical problems of this scale,” said Anna Barker, director and co-founder of the NBDA. “The NBDA was developed not just to relegate the flawed and fragmented approaches to biomarker development processes to history but also to serve as a working example of what purposeful convergence of scientific knowledge and multisector collaboration can accomplish.” Despite a “tsunami of biomarker discovery” seen through the publication of more than 150,000 published papers, the translation of biomarker discovery through development and validation has been severely lacking, organizers say. Fewer than 1.5 protein markers are approved each year by the U.S. Food and Drug Administration and fewer than 100 biomarkers are used in routine clinical practice today. The founders say the standardization they seek will economically boost the diagnostics industry, which has been stymied by an undervaluation of biomarkers in investment and reimbursement, in part because of the “explosion of genomics-based assays and other nonregulated laboratory-developed tests” that have not necessarily undergone technically “robust” processes or independent reproduction. NBDA says setting up demonstration projects is already under way for the development of standards for four classes of biomarkers, including genomics, proteomics, imaging, and complex biomarkers such as biosignatures. Additionally the group is assembling a database of all guidelines, standard operation procedures, and standards for the collection, stewardship, and management of biospecimens. These efforts will culminate in a consensus conference. Takeaway: Standards that address the entire process, from biomarker identification through validation, may improve the utilization of new biomarkers in clinical practice, ultimately benefiting the diagnostics industry. Side Box: Dearth of Validated Markers Seen in Multiple Sclerosis “Validation and clinical application of biomarkers is still an unmet need in multiple sclerosis (MS),” write Manuel Comabella, M.D., and Xavier Montalban, M.D., both from Hospital Universitari Vall d´Hebron in Spain, in a review published in January in Lancet Neurology. The authors argue that given the high degree of heterogeneity in clinical presentation of MS, reliable biomarkers would be particularly useful in better diagnosing and predicting the disease progression. Among the desired properties of molecular biomarkers are diagnostic markers with strong performance characteristics, disease activity biomarkers that are process-specific (neurodegeneration or repair), and treatment-response biomarkers. The authors cite publication of more than 63 exploratory biomarkers but note that there are only five validated biomarkers with a strong evidence base (GWAS genes, human neurofilament heavy chain (NFH), human neurofilament light chain (NEFL), 25-hydroxyvitamin D, and CD56bright natural killer cells) and an additional five clinically useful biomarkers with strong evidence (IgG OB, IgG index, anti-aquaporin 4 antibody (Anti-AQP4), antibodies against JC virus, and anti-varicella zoster virus antibodies).