Issue Panel on the Identification and Implementation of Clinically Meaningful Thresholds for Clinical Outcome Assessments: Challenges and Considerations

ISSUE: Clinically meaningful change remains a topic marked by debate about how we can best define, determine and deploy this concept with clinical outcome assessments (COAs). This session will address key challenges and considerations, including both the scope for harmonization and issues relevant to emerging areas such as digital endpoints.

OVERVIEW: It is now widely recognized that treatment benefits should correspond to changes/outcomes that are tangible and meaningful to patients. It is consequently becoming more common for key trial endpoints to be defined with reference to clinically meaningful thresholds (CMTs) on COAs.

The conceptualization, identification and implementation of CMTs is an area that remains marked by diversity of perspective and approach, resulting in on-going debate and development. These developments are most recently reflected by changes in terminology and approach flagged in FDA’s 2023 draft guidance on ‘Incorporating Clinical Outcome Assessments Into Endpoints for Regulatory Decision-Making’, which stands in contrast to other frameworks/strategies such as IQWiG’s universal 15% threshold. Concurrently, the emergence of digital health technologies as novel COA modalities poses new questions and hurdles.

We are bringing together thought leaders in this field (representing different stakeholders) to discuss key issues on this topic.

The session will commence with an overview [5 min] of the primary concepts (conceptual and methodological) and general sources of heterogeneity/variability in CMTs. Two invited speakers will then present on:

1. The identification and implementation of CMTs within oncology, and the importance of harmonization efforts (such as that led by SISAQOL-IMI) [15min]
2. The novel insights and new challenges in the assessment of meaningful change with digital endpoints [15min].

This will be followed by a discussant [10 min] and Q&A [15 min]. Through the different perspectives offered, this panel will serve to convey (and aspire to inform) the evolving understanding/practice in this important area of clinical outcome research.