SW-2B - The Clone-Censor-Weight Approach: From Basic Principles to Its Transformation in Diverse Exposure and Outcome Scenarios

Background: The clone-censor-weight (CCW) approach is increasingly being used to enhance the validity of target trial emulation studies. However, the standard CCW approach may not be directly applicable in clinical settings and more complex exposure or outcome scenarios, such as cancer therapies, sustained treatment strategies, or cases with an uncertain time zero.

Objectives: - To describe the core components of the CCW approach by using illustrative study examples.
- To explain the transformation of CCW, including surrogate time zero, cancer therapies, or sustained treatment strategies, in order to accommodate different exposure or outcome scenarios.
- To advance the development and application of CCW through an interactive panel discussion, fostering knowledge exchange and implementation insights.

This symposium will benefit attendees seeking to learn the fundamentals of the CCW approach and how to apply it in more complex exposure scenarios, thereby enhancing causal inference within the target trial emulation framework.

Description: This symposium includes presentations by four speakers with extensive experience in the use of CCW method, followed by a moderate panel discussion.

- Daniel Tsai and Edward Lai (5 minutes): Opening

- Kenneth Man (20 minutes): Core components of the CCW Approach
Kenneth Man will introduce the foundational principles of the CCW approach, illustrating how cloning, censoring, and weighting are applied to address immortal time bias.

- Avery Yang (20 minutes): Refining Treatment Assignment Through Surrogate Time Zero
Avery Yang will discuss the rationale and methods for using a surrogate time zero in CCW studies, explaining how it aligns with the index date and how these refinements affect causal inference.

- Charles Gaber (20 minutes): Applying CCW in Cancer Therapies
Charles Gaber will illustrate how the CCW framework can be adapted to complex cancer therapies. He will also show how controlling comorbidity and frailty in oncology settings can strengthen causal inference.

- TBD (20 minutes): Sustained Treatment Strategies for CCW
We will demonstrate why sustained treatment strategies require meticulous specification in the target trial protocol, reflecting real-world clinical practice and enabling researchers to address complex causal questions.

- Jennifer Lund and all speakers (15 minutes) Panel Discussions on Transparent Reporting of Clone-Censor-Weight Studies
Dr. Lund, Daniel Tsai, and Edward Lai will lead a discussion on (1) best practices for reporting CCW studies for reproducibility, (2) defining grace periods and other operational terms, (3) comparing alternative methods addressing immortal time bias, and (4) exploring future methodological innovation and collaboration.