Biomarker Qualification: Toward a Multiple Stakeholder Framework for Biomarker Development, Regulatory Acceptance, and Utilization

Abstract

The discovery, development, and use of biomarkers for a variety of drug development purposes are areas of tremendous interest and need. Biomarkers can become accepted for use through submission of biomarker data during the drug approval process. Another emerging pathway for acceptance of biomarkers is via the biomarker qualification program developed by the Center for Drug Evaluation and Research (CDER, US Food and Drug Administration). Evidentiary standards are needed to develop and evaluate various types of biomarkers for their intended use and multiple stakeholders, including academia, industry, government, and consortia must work together to help develop this evidence. The article describes various types of biomarkers that can be useful in drug development and evidentiary considerations that are important for qualification. A path forward for coordinating efforts to identify and explore needed biomarkers is proposed for consideration.

Micrornas as Pharmacogenomic Biomarkers for Drug Efficacy and Drug Safety Assessment

“…While Rosetta Genomics has described the development of a commercial miRNA-based test that differentiates between the four main types of lung cancer (squamous cell carcinoma, nonsquamous non-small-cell lung cancer, carcinoid and small cell carcinoma) [210], the miRNA-based assay has yet to be approved as an IVD ( in vitro diagnostic) by the FDA. We expect there will be more endeavors in the future to surmount hurdles faced in pursuing ‘biomarker qualification’ [211] and the difficult process in taking a molecular diagnostic from a research discovery to a regulatory-approved clinical diagnostic [212]. …”

Decade-Long Profile of Imaging Biomarker Use in Ophthalmic Clinical Trials

“…Qualification, essential for surrogate endpoints, is the ''fit for purpose'' process aimed to demonstrate not only the link between a biomarker and a biological process but also that, ''within the stated context of use, a biomarker can be relied upon to have a specific interpretation and application in drug development and regulatory review.'' 4,19 Furthermore, the use of imaging data as a primary endpoint in CTs requires particular attention to the need for trial-specific imaging process standards and for centralized, blinded imaging interpretation by RCs. 11 Centralized RCs guarantee collection of high-quality, standardized, and unbiased imaging data that are uniform across different clinical sites and masked to any clinical information.…”

“…First, to select and stratify the study population (diagnostic, prognostic, and predictive biomarkers) and second, to replace true clinically relevant endpoints (surrogate endpoints) predicting the clinical benefit or harm of interest. 1,4,5 The use of biomarkers as surrogate endpoints in very early phases of clinical trials (CTs) to provide proofs of concept is of obvious utility. However, their inclusion in phase III CTs, where potential erroneous decisions based on invalid surrogate endpoints may have broad public health consequences, may pose specific and important challenges.…”

Personalised medicine in asthma: time for action

“…A biomarker is defined as a characteristic that can be measured and evaluated as an indicator of normal or pathological biological processes or the biological response to a therapeutic intervention [20].…”