Implementation of Estimand Framework in Oncology Clinical Trials

• Activity Number: 114 - Applying the ICH E9(R1) Addendum: Practical Considerations in Choosing Estimands, Estimators, and Sensitivity Analyzes
• Type: Topic Contributed
• Date/Time: Monday, July 29, 2019 : 8:30 AM to 10:20 AM
• Sponsor: Biopharmaceutical Section
• Author(s): Kalyanee Appanna* and Bharani Dharan and Yuanbo Song and Ekkehard Glimm
• Companies: Novartis Pharmaceutical Corporation and Novartis Pharmaceuticals and Novartis Pharmaceutical Corporation and Novartis Pharma AG
• Keywords: Estimand; intercurrent event; analytic approach

Abstract

The recently released ICH E9(R1) draft addendum presents a structural framework for the use of estimands in clinical development,aligning trial planning, design,conduct,analysis and interpretation. This promises to have a significant impact on the manner in which multi-disciplinary project teams will undertake drug development.In this presentation we will discuss two case studies based on:i)A randomized phase II study in patients with non-small cell lung cancer in the neoadjuvant setting,with the primary endpoint of major pathological response rate,which is defined as the percentage of subjects with ? 10% residual viable cancer cells detectable in the resected tumor after 6 weeks of treatment and ii)A randomized phase III study in patients with lung neuroendocrine tumors, with the primary endpoint of progression-free survival, defined as the time from the date of randomization to the date of the first documented progression or death due to any cause. In the 2 cases, we will discuss the estimand definitions for the primary endpoint, corresponding analytic approaches including the handling of intercurrent events and strengths and cautions regarding different estimand approaches.