Related papers: Implementing the principal stratum strategy for in…
Intercurrent events, such as treatment switching, rescue medication, dropout, or truncation by death, frequently complicate intention-to-treat analyses in randomized clinical trials. Existing causal inference frameworks typically target…
Under a composite estimand strategy, the occurrence of the intercurrent event is incorporated into the endpoint definition, for instance by assigning a poor outcome value to patients who experience the event. Composite strategies are…
In neoadjuvant trials on early-stage breast cancer, patients are usually randomized into a control group and a treatment group with an additional target therapy. Early efficacy of the new regimen is assessed via the binary pathological…
A draft addendum to ICH E9 has been released for public consultation in August 2017. The addendum focuses on two topics particularly relevant for randomized confirmatory clinical trials: estimands and sensitivity analyses. The need to amend…
The current COVID-19 pandemic poses numerous challenges for ongoing clinical trials and provides a stress-testing environment for the existing principles and practice of estimands in clinical trials. The pandemic may increase the rate of…
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…
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) Addendum provides a framework for defining estimands in clinical trials. Treatment policy strategy is the mostly used…
Since the release of the ICH E9(R1) addendum on estimands, its application in non-inferiority trials has received far less attention than in superiority settings. A key conclusion from Lynggaard et al. was that the "choice of…
Randomized controlled trials are considered the gold standard to evaluate the treatment effect (estimand) for efficacy and safety. According to the recent International Council on Harmonisation (ICH)-E9 addendum (R1), intercurrent events…
In clinical trials, patients may discontinue treatments prematurely, breaking the initial randomization and, thus, challenging inference. Stakeholders in drug development are generally interested in going beyond the Intention-To-Treat (ITT)…
The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…
In many medical studies, an ultimate failure event such as death is likely to be affected by the occurrence and timing of other intermediate clinical events. Both event times are subject to censoring by loss-to-follow-up but the nonterminal…
Recurrent events often serve as key endpoints in clinical studies but may be prematurely truncated by terminal events such as death, creating selection bias and complicating causal inference. To address this challenge, we develop a Bayesian…
Externally controlled trials are crucial in clinical development when randomized controlled trials are unethical or impractical. These trials consist of a full treatment arm with the experimental treatment and a full external control arm.…
The treatment effect in a specific subgroup is often of interest in randomized clinical trials. When the subgroup is characterized by the absence of certain post-randomization events, a naive analysis on the subset of patients without these…
A platform trial is an innovative clinical trial design that uses a master protocol to evaluate multiple treatments, where patients are often assigned to different subsets of treatment arms based on individual characteristics, enrollment…
Average and conditional treatment effects are fundamental causal quantities used to evaluate the effectiveness of treatments in various critical applications, including clinical settings and policy-making. Beyond the gold-standard…
Causal inference methods are gaining increasing prominence in pharmaceutical drug development in light of the recently published addendum on estimands and sensitivity analysis in clinical trials to the E9 guideline of the International…
Intercurrent events (ICEs) and missing values are inevitable in clinical trials of any size and duration, making it difficult to assess the treatment effect for all patients in randomized clinical trials. Defining the appropriate estimand…
In causal inference, principal stratification is a framework for dealing with a posttreatment intermediate variable between a treatment and an outcome, in which the principal strata are defined by the joint potential values of the…