ICH guide provides clarity on estimands, sensitivity analyses

Regulatory NewsRegulatory News | 31 January 2022 |  By 

The International Council for Harmonization (ICH) has issued ICH E9 (R1) training materials meant to improve the planning, design, analysis and interpretation of clinical trials by defining suitable estimands.
The 238-page guide is meant to accompany an earlier addendum that presents a structured framework to link trial objectives to a suitable design; the addendum took effect in 30 July 2020 (RELATED:  ICH E9(R1) and S5(R3) to Take Effect in EU by End of July, Regulatory Focus, 18 February 2020).
Estimands is defined as a “precise description of the treatment effect reflecting the clinical questions posed by a given trial objective [and] summarizes at a population level what the outcomes would be in the same patients under different treatment conditions being compared.”
Without a precise description of the trial objective and the treatment effect, there is the risk that the study will be designed inappropriately, and the statistical analyses will be “misaligned” with the trial’s objective, according to ICH.
The training materials also are meant to facilitate dialogue regarding the treatment effects that a clinical trial seeks to estimate between disciplines, such as clinician and statistician, or between a sponsor and regulator.
The bulk of the guide includes examples dealing with estimands and sensitivity analyses in clinical trials, based on the experience of Expert Working Group (EWG) members. One case study discusses the outcome of a treatment for type II diabetes compared to no treatment. Another real-life example discusses a cancer drug and how interpreting the trial results was difficult as deaths were handled as missing data.
The training guide calls for “greater precision on what is labelled as ‘missing data’,” adding that by “having clarity in the estimand gives a basis for planning which data need to be collected and hence which data, when not collected, present a missing data problem to be addressed.”

ICH E9(R1) training materials


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Tags: E9(R1), estimands, ICH

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