Censoring and censoring mechanisms in oncology in light of the estimands framework

03/03/2022
by   Jonathan Siegel, et al.
0

In oncology clinical trials with time-to-event endpoints, censoring rules have traditionally been defined and applied following standard approaches based on longstanding regulatory guidelines. The estimand framework (addendum to the ICH E9 guideline) calls for precisely defining the treatment effect of interest to align with the clinical question of interest, and requires predefining the handling of intercurrent events that occur after treatment initiation and either preclude the observation of an event of interest or impact the interpretation of the treatment effect. In the context of time to event endpoints, this requires a careful discussion on how censoring rules are applied. This paper explains the importance of distinguishing censoring concepts that have traditionally been merged. Specifically, noumenal censoring as an estimation method to address an intercurrent event which influences the clinical question itself (i.e. defines the pre-specified estimand), distinguishing it from phenomenal censoring that addresses administratively missing information (i.e. defines missing data handling in the estimate). Strategies for dealing with the most relevant intercurrent events, the need for close alignment of the clinical question of interest and study design, impact on data collection and other practical implications will be discussed. The authors recommend defining trial-specific rules as well as considering when noumenal and phenomenal censoring is used. These considerations also apply to defining relevant and interpretable sensitivity and supplementary analyses.

READ FULL TEXT

page 1

page 2

page 3

page 4

11/20/2017

Treatment Effect Quantification for Time-to-event Endpoints -- Estimands, Analysis Strategies, and beyond

A draft addendum to ICH E9 has been released for public consultation in ...
07/09/2021

Hypothetical estimands in clinical trials: a unification of causal inference and missing data methods

The ICH E9 addendum introduces the term intercurrent event to refer to e...
12/11/2021

Multiply robust estimators in longitudinal studies with missing data under control-based imputation

Longitudinal studies are often subject to missing data. The ICH E9(R1) a...
12/19/2020

Revisiting ICH E9 (R1) during the COVID-19 pandemic

The current COVID-19 pandemic poses numerous challenges for ongoing clin...
08/31/2021

Comments on The clinical meaningfulness of a treatment's effect on a time-to-event variable

Some years ago, Snapinn and Jiang[1] considered the interpretation and p...
06/27/2020

Impact of the adjustment of stratification factors on time-to-event analyses

In a stratified clinical trial design with time to event end points, str...