The Pharmaceutical Industry Working Group on Estimands in Oncology in collaboration with PHUSE has started a Safety Task Force on estimands in safety, focusing on oncology. The Task Force will formulate recommendations regarding formulation and use of safety estimands in oncology clinical trials as well as identifying applications of estimands principles to help improve general safety reporting. Recommendations will include trial design, data collection, and analysis issues and ways to integrate clinical, statistical, operations, and data management aspects of study design and execution cooperatively. Key task force activities will include a dive into literature on the subject, formulation of recommendations, development of white papers, and preparation of journal manuscripts and conference presentations. For more information, please contact Jonathan Siegel at Jonathan.siegel@bayer.com. For information on the Pharmaceutical Industry Working Group on Estimands in Oncology, please visit www.oncoestimand.com or contact Working Group co-chairs, Degtyarev Evgeny at evgeny.degtyarev@novartis.com or Kaspar Rufibach at kaspar.rufibach@roche.com. |
| Bibliography |
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| Assessing Adverse Events in Clinical Trials During the Era of the COVID-19 Pandemic |
| Cabarrou B et al. Modernizing adverse events analysis in oncology clinical trials using alternative approaches: rationale and design Adverse Events Analysis in Oncology Clinical Trials Using Alternative Approaches: Rationale and Design of the MOTIVATE trialTrial. Investigational New Drugs 38:1879–1887 (2020) |
| Rockhold et al. University of Pennsylvania 11th annual conference on statistical issues in clinical trialsAnnual Conference on Statistical Issues in Clinical Trials: Estimands, missing data and sensitivity analysis (morning panel sessionMissing Data and Sensitivity Analysis (Morning Panel Session) Clinical Trials 16: 350–362 (2019) |
| Unkel S, Amiri M, Benda N, et al. On estimands Estimands and the analysis Analysis of adverse events Adverse Events in the presence Presence of varying follow-up times Varying Follow-Up Times within the benefit assessment Benefit Assessment of therapiesTherapies. Pharm Stat. 2019;18:166-183. Doi:10.1002/pst.1915 |
Yuan et al., Estimands in safety Safety and benefitBenefit-risk evaluationRisk Evaluation. In Wang et al. eds., Quantitative Drug Safety and Benefit-Risk Evaluation. Chapman and Hall/CRC (2021). |
| Yang, F., Wittes, J. and Pitt B. Beware of on-treatment safety analysesOn-Treatment Safety Analyses. Clinical Trials 16:63-70 (2019). |
Publications – Safety estimands mentionedEstimands Mentioned |
| Akacha M, Bretz F, Ruberg S. Estimands in clinical trials Clinical Trials – broadening Broadening the perspectivePerspective. Stat Med. 2017;36(1):5-19. Doi:10.1002/sim.7033 |
| Ratitch B, Bell J, Mallinckrodt C, et al. Choosing Estimands in Clinical Trials: Putting the ICH E9(R1) Into Practice. Ther Innov Regul Sci. 2020;54(2):324-341. Doi:10.1007/s43441-019-00061-x |
| Siegel JM, Grinsted L, et al. Censoring and censoring mechanisms Censoring Mechanisms in oncology Oncology in light Light of the estimands framework Estimands Framework (2022a). Submitted. Arxiv: https://arxiv.org/abs/2203.01781 |
| Siegel JM, Weber HJ., Englert S. The Role of Occlusion: Potential Extension of the ICH E9 (R1) Addendum on Estimands and Sensitivity Analysis for Time-to-Event Oncology Studies (2022b). Submitted.: |
| Hofner, B. Safety analyses: The Cinderella of biostatisticsBiostatistics? A regulatory perspectiveRegulatory Perspective. EFSPI Statistics Leaders Meeting 2020. |
| Collopy, M. Challenges of safety and and dual benefitdual benefit--risk risk estimandsSafety and Dual Benefit Risk Estimands. BIOP 2019. |
| Torres, C. Safety estimandsEstimands: A regulatory perspectiveRegulatory Perspective. BIOP 2019. |
| PHUSE white paper White Paper - Analyses & Displays Associated with Adverse Events: Focus on Adverse Events in Phase 2-4 Clinical Trials and Integrated Summary |
| PHUSE white paper White Paper - Analysis and Displays Associated with Safety Topics of Interest- Focus on Phase II to IV Clinical Trial |
| PHUSE Computational Science Symposium 2020 - Planning and Interpreting Safety Analyses for Integrated Summaries Workshop |
| Nilsson, M., Crowe, B., Anglin, G., et al. (2020). Clinical Trial Drug Safety Assessment for Studies and Submissions Impacted by COVID-19. Statistics in Biopharmaceutical Research, 12:4, 498–505. https://www.tandfonline.com/doi/full/10.1080/19466315.2020.1 804444. |