Towards Improved Biomarker Analysis and Validation
During Oxford Global’s annual Biomarkers UK: In Person event on 3rd and 4th May 2022 in London, UK, senior-level experts united to partake in a thought-provoking forum aimed at delivering a forward-looking perspective on the latest technologies and strategies impacting biomarker research today.
Among the key figures to present at the conference were Steve Hoffmann, Associate Vice President and Research Partnerships Director for the Biomarkers Consortium at the Foundation for the National Institutes of Health and Steven Piccoli, Associate Vice President at Sun Pharmaceutical Advanced Research Company. Together Hoffmann and Piccoli contributed to a panel discussion exploring the criteria for the improved qualification of biomarkers.
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Attended by leading Pharma, biotech, and academic delegates, both on-site and digitally, the panel session addressed the following critical issues: biomarkers and their context of use, evidentiary standard, and regulatory pathways for biomarkers.
Biomarkers and Contexts of Use
The context of use for any biomarker is critical to the understanding of its potential. In particular, the context of use is a concise description of the biomarker’s specified utility in drug development and is required for FDA approval. The description must include two key components: the most-appropriate biomarker category and its intended use in drug development. As Steve Hoffmann, Associate Vice President and Research Partnerships Director for the Biomarkers Consortium at the Foundation for the National Institutes of Health, explained, “supported context of use is a critical strategic approach for an effective biomarker proposal.”
“Whether the biomarker shows potential as a diagnostic or prognostic marker, or even a tool to measure pharmacodynamic response, it is important to provide the data to prove it,” Hoffmann confirmed. “Regulatory bodies like the FDA also require specificity regarding the evidenced context of use such as if it is disease-related or has a lot of heterogeneity to identify sub-types.” Other specificity criteria should address contexts, including intention to stratify patients for entry into clinical trials.
Should the proposed biomarkers not yet be well-defined enough to reach a definitive categorisation in a letter of intent, additional steps must be taken. For example, it will be necessary to investigate the clinical outcome and “propose the right measure of endpoints to accurately assess it.” Hoffmann continued by indicating that it is a “phase-wise approach, requiring validation of either the prognostic or diagnostic biomarkers to then become adopted by the wider community and field during clinical trials.” This subsequently generates a plethora of data which will likewise support the context of use and reveal different avenues of use.
Navigating Strategic Partnerships during Biomarkers Qualification
Using third-party mediators across the sector is a sure-fire way to further aid biomarker validation and qualification. A consortia partnership provides consultation and advice services to bring different groups working in the same area together. Collaborative efforts can take the form of either public or private partnership programmes.
"The digital revolution has meant the requirement of better transparency from a regulatory perspective"
“It is unfortunate that many biomarkers these days are qualified (only) in the context of a drug submission to an agency,” Steven Piccoli, Associate Vice President at Sun Pharmaceutical Advanced Research Company said. Private partnerships such as these often result in closed-data results where findings are not actively shared. By comparison, public partnerships are more utilitarian in their approach to drug development.
Moreover, public partnerships also publicise data to promote biomarker qualification on a broader scale. They are “pre-competitive” and generate information that is “freely available,” Piccoli explained. “There needs to be a willingness to share,” he continued — “without it certain safety measures remain under the radar and conducive processes buried. Being selfless in the qualification process means we can help the entire industry work towards a similar goal.”
Regulatory Pathways for Biomarkers
To achieve regulatory qualification for biomarkers, a high level of analytic validation must be achieved. Gaining acceptance by the US Food and Drug Administrator (FDA) and European Medicine Agency (EMA), depends on a fit-for-purpose criteria. Key considerations are qualification stringency, biomarker reproducibility, and robusticity.
The recent industry uptake of artificial intelligence and novel digital technologies means certain security measures and controls must also be evidenced during validation. As Hoffmann explained, “the digital revolution has meant the requirement of better transparency from a regulatory perspective. Questions like how to baseline and control digital measures need to be answered sufficiently.” Treatment response data similarly provides a critical indication of a biomarker’s utility.
Biomarker Analysis of Tomorrow
Maintaining a consistent framework for biomarker qualification and analysis is critical. “Analytical and clinical validation efforts must stay the same,” Hoffmann confirmed. “Having a well-thought-out and steady framework will enable an equally viable model for development.” This will also prove useful for biomarker qualification programs and confirmation during clinical trials.
Whilst the current timescale of preclinical qualification for human clinical trials currently stands at around 17 years, the hope is to streamline procedures in the future. “It may be slow moving now, but the path to biomarker qualification will get easier, faster, and more accessible,” Hoffmann concluded.
Want to stay up to date with the latest Biomarker news? Register now for Oxford Global’s flagship event, Biomarkers UK. This is a must-attend forum covering the latest trends transforming biomarker and translational research.
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