The European Medicines Agency (“EMA”) has published a checklist of the essential considerations to be addressed for successful qualification of novel methodologies.
Background information
EMA provides specific scientific advice intended to support the qualification of innovative development methods for a specific intended use in the context of research and development of medicinal products. EMA’s qualification of novel methodologies is a voluntary, scientific pathway which covers methodologies such as biomarkers, imaging methods and clinical outcome assessments.
The EMA checklist
The EMA essential considerations checklist is intended to highlight important points that have been identified as common major challenges compromising the successful qualification of innovative methods. Although the checklist addressed important points to be taken into consideration it does not provide comprehensive guidance. EMA advises that qualification advice should be requested from EMA. This is due to the existence of a wide variety of potential specific scientific and regulatory considerations.
The checklist provides guidance in several points, including:
- Definition of the Context(s) of Use (CoU)
- Selection of Endpoint(s)
- Statistical Analysis Plan (SAP)
- Demonstration of clinical utility
- Standard of truth / surrogate standard of truth
- Appropriateness of the analytical platform
- Other considerations with available regulatory guidance
In particular, EMA’s essential considerations checklist underlines that the CoU must include a full, clear and concise description of the way a novel methodology is to be used. According to the checklist, the CoU is the critical reference point for the assessment of any qualification application. The checklist requires that the study design and data analysis support the CoU. Moreover, statistical planning must be appropriate following a pre-specified SAP and the exploratory studies can be included as appropriate. Applicants for qualification of novel methodologies should integrate within their application the elements described at EMA’s essentials considerations checklist.
The checklist provides that, where assessment of the standard of truth is not possible or is unethical, a surrogate standard of truth must be established and justified.
In addition, the selection of endpoints requires demonstration of diagnostic and prognostic performance, the characterisation of the levels of positive or negative predictive value and the demonstration of the sensitivity to detect change reflecting the clinical status of patients. Guidance is also provided in relation to SAP.
The checklist requires that, where assessment of the standard of truth is not possible or is unethical, a surrogate standard of truth must be established and justified.
Applicants for qualification of novel methodologies should integrate within their application the elements described at EMA’s essentials considerations checklist.