Aligning the Alzheimer’s biomarker validation framework to technology readiness levels

Abstract

AbstractBackgroundTechnology readiness levels (TRL), used in technological R&D, also frame European Commission biomedical funding frameworks. Providing an adaptation to biomarker development would improve communication with industry, align stakeholders and professionals, reduce risk of development failure, costs and waste. Here, we aim to align TRLs with the Strategic Biomarker Roadmap (SBR) defined to validate biomarkers for Alzheimer’s disease (AD) and related disorders.MethodWe analyzed the NASA definition of TLR phases and a previously proposed adaptation to the biomedical field. We drafted an alignment of TRLs with the SBR Phases and Aims. We refined such alignment through discussion and consensus among coauthors and outlined discrepancies, gaps and SBR limitations relative to the TRL framework, to improve the development process for future biomarkers.ResultThe SBR covers all of the 9 TRLs. The demonstration of Analytical Validity entails TRLs_1‐4. Specifically, the SBR Phase_1 includes TRLs_1‐2; Phase_2 Primary Aim (PA) corresponds to TRL_3, and Phase_2 Secondary Aims (SAs) to TRL_4. Clinical Validity entails TRLs_5‐8. Specifically, the SBR Phase_3 corresponds to TRL_5, while TRLs_6‐8 correspond respectively to Phase_4 PA, SAs, and full completion. Demonstration of Clinical Utility corresponds to TRL_9. Despite such correspondence, the SBR entails only biomarker diagnostic performance and utility. Aspects like manufacturing and usability, fundamental in the TRL framework as well as in the previous biomedical adaptation, are still lacking. The definition of tools (e.g., Target Product Profile, introduced at TRL 3 in the biomedical adaptation) may help complement the SBR in this direction.ConclusionThe SBR and TRLs follow a consistent sequence despite different pacing and granularity, SBR steps corresponding to one‐to‐multiple TRLs. Targeting such inconsistencies and upgrading the SBR validation roadmap into a development roadmap, entailing manufacturing, usability, and an integrated procedure to assess cost‐effectiveness and plan implementation requires a structured dialogue with industry partners and other stakeholders, like regulators. Such attempt to evolve the SBR from a linear to a multi‐dimensional model may help boost the efficiency of translational research and our response to the global priority of dementia.