Weighted Approach for Estimating Effects in Principal Strata with Missing Data for a Categorical Post-Baseline Variable in Randomized Controlled Trials

01/12/2021
by   Shengchun Kong, et al.
0

This research was motivated by studying anti-drug antibody (ADA) formation and its potential impact on long-term benefit of a biologic treatment in a randomized controlled trial, in which ADA status was not only unobserved in the control arm but also in a subset of patients from the experimental treatment arm. Recent literature considers the principal stratum estimand strategy to estimate treatment effect in groups of patients defined by an intercurrent status, i.e. in groups defined by a post-randomization variable only observed in one arm and potentially associated with the outcome. However, status information might be missing even for a non-negligible number of patients in the experimental arm. For this setting, a novel weighted principal stratum approach is presented: Data from patients with missing intercurrent event status were re-weighted based on baseline covariates and additional longitudinal information. A theoretical justification of the proposed approach is provided for different types of outcomes, and assumptions allowing for causal conclusions on treatment effect are specified and investigated. Simulations demonstrated that the proposed method yielded valid inference and was robust against certain violations of assumptions. The method was shown to perform well in a clinical study with ADA status as an intercurrent event.

READ FULL TEXT
POST COMMENT

Comments

There are no comments yet.

Authors

page 1

page 2

page 3

page 4

11/22/2021

Monotonicity assumptions in estimating the treatment effect for a principal stratum

In addition to the treatment effect for all randomized patients, sometim...
09/13/2019

Bayesian analysis of longitudinal studies with treatment by indication

It is often of interest in observational studies to measure the causal e...
08/12/2020

Principal Stratum Strategy: Potential Role in Drug Development

A randomized trial allows estimation of the causal effect of an interven...
07/16/2021

Clarifying Selection Bias in Cluster Randomized Trials: Estimands and Estimation

In cluster randomized trials, patients are recruited after clusters are ...
03/22/2021

A New Causal Approach to Account for Treatment Switching in Randomized Experiments under a Structural Cumulative Survival Model

Treatment switching in a randomized controlled trial is said to occur wh...
10/01/2020

A note on the amount of information borrowed from external data in hybrid controlled trials with time-to-event outcomes

In situations where it is difficult to enroll patients in randomized con...
This week in AI

Get the week's most popular data science and artificial intelligence research sent straight to your inbox every Saturday.