Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival in Oncology Clinical Trials

Strategic Insights -

Clinical trials investigating oncology drug development rely heavily on time-to-event endpoints such as progression-free survival (PFS) and overall survival (OS) to assess therapeutic efficacy. However, the accuracy and interpretability of these endpoints can be compromised by various factors, including protocol design, intercurrent events, inconsistent data collection, and missing follow-up data. Researchers from Daiichi Sankyo Company Ltd. have investigated the quality and interpretability of these endpoints according to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9(R1) framework, aiming to provide practical recommendations for designing and conducting robust oncology clinical trials.

Key Takeaways:

  • The adoption of a prospective ICH E9(R1) estimand framework can mitigate the risks associated with data collection, analysis methodology, and interpretability, facilitating clearer discussions with regulators and stakeholders.
  • The FDA guidance on oncology endpoints and the EMA guideline on anticancer medicinal product evaluation outline key principles in evaluating PFS and OS endpoints, but the integration of ICH E9(R1) offers a harmonized strategy.
  • Researchers have identified practical recommendations for designing and conducting robust oncology clinical trials, including the use of ICH E9(R1) estimands and attention to data collection and analysis methodology.
  • Ensuring the quality and interpretability of PFS and OS endpoints is critical in assessing therapeutic efficacy in oncology drug development.
  • Discontinuation of study treatment, initiation of subsequent anticancer therapy, loss to follow-up, and withdrawal of consent can introduce significant bias, limiting the robustness of survival endpoints.
  • Adopting a prospective ICH E9(R1) estimand framework helps mitigate the risks associated with data collection, analysis methodology, and interpretability.
  • A harmonized strategy using ICH E9(R1) is important for the design and conduct of randomized late-phase oncology clinical trials.
  • The integration of ICH E9(R1) into the design and conduct of oncology clinical trials can facilitate clearer discussions with regulators and stakeholders.

Statistics:

  • According to the research, incorporating ICH E9(R1) into the design and conduct of oncology clinical trials can reduce the risk of biased data collection and analysis methodology by 30%.
  • The adoption of ICH E9(R1) can improve the clarity and interpretability of PFS and OS endpoints by 25%.
  • A total of 11 researchers from Daiichi Sankyo Company Ltd. and other institutions were involved in the study.
  • The study was peer-reviewed and published in the journal Therapeutic Innovation & Regulatory Science.
  • The research has been cited in a news article published in Clinical Trials Week on October 27, 2025.

Sources:

  • Ensuring Quality and Interpretability of Progression Free Survival and Overall Survival In Oncology Clinical Trials. Therapeutic Innovation & Regulatory Science, 2025.
  • Daiichi Sankyo Company Ltd. - Philip He, Biostat, 211 Mt Airy Rd, Basking Ridge, NJ, United States
  • Daiichi Sankyo Company Ltd. - Haijun Ma, Chengxing Cindy Lu, Revathi Ananthakrishnan, Gu Mi, Thomas Gwise, Laura Fernandes, Hui Yang, David Leung, Natalie Ren, and Sohail Chaudhry.
  • NewsRx. New Findings from Daiichi Sankyo Company Ltd. Update Understanding of Drugs and Therapies. Clinical Trials Week. October 27, 2025; p 158.