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Estimands and their Implications on Clinical Studies

Last year, Paul Terrill, Associate Principal of Strategic Consulting at Cytel, presented an engaging webinar on the topic of Estimands. The webinar covered a range of issues from what is an estimand to how to structure early discussions on estimands. On popular demand, Paul will re-run this webinar on August 13, 2020, and add recent developments on this topic. He will share the bottom-line on estimands and discuss their implications for a trial's objectives, design, data collection, statistical analyses and conclusions. Paul will also share his guidance on managing the communication about estimands between multiple internal stakeholders, gaining internal buy-in, and ensuring that a trial’s objectives, design, conduct, analysis and interpretation are in line with the addendum. Register today by clicking on the button.

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Continue reading this blog to understand the concept of Estimands, their role in clinical trials and the purpose of the final ICH E9(R1) addendum.

According to ICH E9(R1), an estimand is “a precise description of the treatment effect reflecting the clinical question posed by the trial objective. It summarizes at a population-level what the outcomes would be in the same patients under different treatment conditions being compared". In clinical trials, we generally aim to assess treatment effects, and for that we have to be very precise on which treatment effect we plan to estimate. The estimand language and framework helps us to state this more clearly. To define the estimand precisely, we need to specify the following four attributes:

  1. Our population of interest
  2. Endpoint of interest
  3. The summary measure we want to base our comparison on
  4. Intervention effect of interest

The ICH E9(R1) addendum on estimands and sensitivity analysis was released in November 2019 to provide a structured framework to strengthen the dialogue between disciplines involved in the formulation of clinical trial objectives, design, conduct, analysis and interpretation, as well as between sponsor and regulator regarding the treatment effect(s) of interest that a clinical trial should address.* In simpler terms, it provides a structured framework to link trial objectives to a suitable trial design and to tools for estimation and hypothesis testing. It emphasizes the importance of clearly describing the benefits and risks of a treatment for a given medical condition. An estimand also describes the quantity to be estimated to address a specific study objective. It is used to translate the trial objective into a precise definition of the treatment effect to be estimated. Understanding and getting the clarity on the effect that a study is targeting can help expedite the approval. One recent example where the addendum has proven its value is in the case of COVID-19. We are all very concerned about assessing the impact of COVID-19 on our trials and the estimand framework provides an effective way to start having this conversation.

The nature and implementation of an Estimands Framework is a cross-disciplinary topic with sizeable clinical and regulatory implications, and its vital importance is not just restricted to statisticians. The estimand framework provides an opportunity to design better trials and allows an organization’s statistical leadership to engage with their clinical team and other internal and external stakeholders, quite early on. This enables a clear formulation of the goal of the clinical trial.

To get more insights on the topic of estimands and understand their impact on clinical data, statistical analyses and the outcome of a study, register for Cytel’s upcoming webinar, “Estimands: Not Just a Statistical Issue”, by clicking on the button.

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