英文_EFPIA_关于EMA认证一种新方法的提案_15页_552kb

QoNM: Digital Measure (COA) - March 2025

EFPIA Proposal for EMA Qualification of Novel Methodology

1. Overview

• Purpose: Provides a template for submitting requests for qualification advice on novel methodologies for clinical outcome assessments (COA) using digital health technologies (DHT). The focus is on methodologies intended as COAs or digital COAs, excluding eCOA or DHT CE-marking.
• Template Use: Not required to seek a full EMA qualification (SV95C); it can be adapted for other regulatory or innovation interactions.
• Scope: Out-of-scope are qualifications for eCOA or medical-purpose evidence for DHT CE-marking.

2. Key Terminology

• Digital Measure: A value derived from DHT data used as an endpoint in trials.
• Digital Clinical Outcome Assessment (COA): Assessment of clinical outcomes derived from DHT data.
• Context of Use (CoU): Describes how the digital COA will be used in drug development, including target populations, timing, and device details.
• Meaningful Aspect(s) of Health (MAH): Patient-defined and clinically relevant aspects to improve or prevent disease-related changes.

3. Qualification Briefing Book Structure

1. Executive Summary

• Short description of the novel methodology, its context, and evidence.

2. Rationale for Seeking Advice

• Purpose: Examples include seeking qualification for a primary endpoint in a specific disease.

4. Meaningful Health Aspects, COI, and CoU

4.1 Proposed Name and DHT

• Specify the proposed digital COA name and DHT(s).

4.2 MAH and COI

• MAH: Patient-defined health aspects (e.g., improved ambulatory speed).
• COI: The concept (e.g., muscle strength) or outcome to measure.

4.3 Context of Use (CoU)

• Definition: Use within trials, target population, study design, timing, and data flow.

4.4 Endpoint Definition

• Objective: Describe the endpoint’s purpose, such as evaluating the effect of a drug.

4.5 Target Label Claim

• Alignment: Defines the intended role in regulatory approval.

5. Disease Background

5.1 Disease Overview

• Disease Burden: Natural history, unmet needs, and limitations of current tools.

5.2 Patient Experience

• Patient-Centered Perspective: Symptoms, burden, and meaningful outcomes.

6. Novelty and Impact of Digital COA

6.1 Current Tools

• Limitations: Existing COAs and gaps (e.g., no direct measures of COI).

6.2 Gaps Addressed

• Benefits: Advantages of the proposed digital endpoint, supported by preclinical/clinical data.

7. Validation

7.1 Verification

• Accuracy/Precision: Bench evaluation for sensor and software.

7.2 Analytical Validation

• Structure: Study objectives, design, protocols, sample size, and statistical analysis for endpoints.

7.3 Clinical Validation

• Structure: Parallel to analytical validation, demonstrating the endpoint’s relevance and accuracy in patient populations.

7.4 Meaningful Change

• Identification: Thresholds derived from clinical/top-down methods.

7.5 Usability/Wearability

• Evidence: User experience data to ensure practicality and reliability in target populations.

8. Gaps in Development

• Known Limitations: Identified challenges for the measure or DHT.

9. Conclusion

• Summary: Overview of the methodology, validation, usability, and gaps.

References

Includes abbreviations, tables, figures, and key citations (e.g., Walton et al., EMA guidance).

Summary:
This document outlines a structured approach for companies to submit a qualification request for novel digital clinical outcome assessments (COAs) to the EMA. It defines key terminology and emphasizes patient-centricity, validation studies (verification, analytical, clinical), usability, and meaningful change thresholds. The template ensures comprehensive evidence is provided to support qualification, addressing gaps in current COA methods.