2 I have never heard of estimands - where should I start?

2.1 What is an estimand?

From the glossary of the ICH E9: estimands addendum:

A precise description of the treatment effect reflecting the clinical question posed by the trial objective. It summarises at a population-level what the outcomes would be in the same patients under different treatment conditions being compared.

2.2 Where should I start?

This entire page is a starting point. Further,

  • 3min intro video: What is an estimand in a clinical trial: The PIONEER 1 example, based on Aroda et al. (2019).
  • 3min intro video: Why the addendum is needed and what it is about (Kaspar Rufibach).
  • PSI EIWG Webinar: PIONEERing estimands in Clinical Research: Introductory webinar that is intended for anyone working in clinical trials: Clinicians, Regulators, Investigators, Academics, Ethics Committees, Statisticians.
  • Introductory session on endpoints and estimands for clinicians, co-organized by ANVISA (Brazilian Health Authority) and interfarma.
  • Relevant publications that are to a large extent non-statistical and are a good starting point as well:
    • Degtyarev et al. (2019): Example of putting the addendum into action in oncology, appeared in JCO.
    • Aroda et al. (2019): Example of putting a continuous endpiont in the estimand framework. Pre-addendum (treatment attribute is missing), but still informative.
    • Sun et al. (2021): Illustrates implementation of the framework in hematology.
    • Casey et al. (2021): Illustrates implementation of the framework in solid tumors.
    • Lawrance et al. (2020): Illustrates implementation of the framework for a PRO endpoint. See also the publications tab.

References

Aroda, V. R., T. Saugstrup, J. B. Buse, M. Donsmark, J. Zacho, and M. J. Davies. 2019. “Incorporating and interpreting regulatory guidance on estimands in diabetes clinical trials: The PIONEER 1 randomized clinical trial as an example.” Diabetes Obes Metab 21 (10): 2203–10.

Casey, Michelle, Evgeny Degtyarev, Maria Jose Lechuga, Paola Aimone, Alain Ravaud, Robert J. Motzer, Feng Liu, et al. 2021. “Estimand Framework: Are We Asking the Right Questions? A Case Study in the Solid Tumor Setting.” Pharmaceutical Statistics 20 (2): 324–34. https://doi.org/https://doi.org/10.1002/pst.2079.

Degtyarev, Evgeny, Yiyun Zhang, Kapildeb Sen, David Lebwohl, Mouna Akacha, Lisa V. Hampson, Bjoern Bornkamp, Antonella Maniero, Frank Bretz, and Emmanuel Zuber. 2019. “Estimands and the Patient Journey: Addressing the Right Question in Oncology Clinical Trials.” JCO Precision Oncology, no. 3: 1–10. https://doi.org/10.1200/PO.18.00381.

Lawrance, Rachael, Evgeny Degtyarev, Philip Griffiths, Peter Trask, Helen Lau, Denise D’Alessio, Ingolf Griebsch, Gudrun Wallenstein, Kim Cocks, and Kaspar Rufibach. 2020. “What Is an Estimand & How Does It Relate to Quantifying the Effect of Treatment on Patient-Reported Quality of Life Outcomes in Clinical Trials?” J Patient Rep Outcomes 4 (1): 68. https://doi.org/10.1186/s41687-020-00218-5.

Sun, S., J. Weber, E. Butler, K. Rufibach, and S. Roychoudhury. 2021. “Estimands in Hematology Trials.” Pharm. Stat., to Appear. https://arxiv.org/abs/2010.00957.