Design of a card-based operational framework for the implementation of inclusive representation in clinical trials

Despite growing recognition that trial populations should reflect the broad range of people who will receive therapies, implementation of representative enrollment remains inconsistent. Existing frameworks often lack role-specific guidance, phase-specific actions, and actionable tools to support sponsors-referring specifically to pharmaceutical companies-in embedding inclusive representation (IR) across the trial life cycle. To address these gaps, we developed a card-based operational framework (CBOF) that assigns clear responsibilities, aligns with regulatory expectations, and supports implementation at both the trial and organizational levels.

We conducted a four-phase methodological study to design the CBOF. First, a structured scoping review identified existing frameworks tackling diverse representation, health equity, and inclusion, as well as guidance documents. Second, we performed a comparative matrix-based analysis to assess operational completeness, surface gaps across 15 frameworks, and to develop the design brief of the developed framework. Third, we held a 120-min expert advisory board consultation with representatives from regulatory, academic, patient advocacy, and pharmaceutical domains to validate the design brief. Fourth, we developed the CBOF using a 5W1H (What, Why, Who, When, Where, How) structure to inform framework content and format.

The resulting CBOF consists of a modular, card-based tool set organized across nine inclusive representation "IR" categories: seven focused on trial-level design and two on organizational readiness. It includes editable Core Cards to prompt IR planning, Support Cards to provide guidance and role clarification, a library of 349 implementation tactics, and a KPI catalogue to track progress. The framework specifies who is responsible, when and where actions should occur across the product life cycle (discovery through life cycle management) and the clinical trial stages (planning to read out), and how each activity can be executed. It assigns IR-related responsibilities to 15 functional teams and includes step-by-step workflows and decision-question pathways. Expert feedback affirmed the framework's usability, relevance, and completeness, while also informing improvements such as adaptability, integration of digital tools, and expanded guidance on performance metrics.

This framework has been designed to support companies and sponsors, specifically referring to pharmaceutical companies interested in strengthening the representation of real-world patients in clinical trials. The CBOF translates diverse representation, health equity, and inclusion principles into structured, actionable guidance for clinical trial sponsors. It addresses longstanding operational gaps by combining decision-support tools, role-specific delegation, and measurable KPIs across development phases and trial stages. While further validation in real-world settings is needed, the framework represents a practical advancement in operationalizing inclusive trial design and supporting sponsors in meeting regulatory and ethical expectations.