Related papers: Combining the target trial and estimand frameworks…
Randomized controlled trials (RCTs) face inherent limitations, such as ethical or resource constraints, which lead to a limited number of study participants. To address these limitations, recent research endeavors have sought to incorporate…
In causal inference, the correct formulation of the scientific question of interest is a crucial step. Here we apply the estimand framework to a comparison of the outcomes of patient-level clinical trials and observational data to help…
Observational studies provide the only evidence on the effectiveness of interventions when randomized controlled trials (RCTs) are impractical due to cost, ethical concerns, or time constraints. While many methodologies aim to draw causal…
While randomized controlled trials (RCTs) are the gold standard for estimating treatment effects in medical research, there is increasing use of and interest in using real-world data for drug development. One such use case is the…
Randomized controlled trials (RCT) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the…
The creation of the ICH E9 (R1) estimands framework has led to more precise specification of the treatment effects of interest in the design and statistical analysis of clinical trials. However, it is unclear how the new framework relates…
Externally controlled trials (ECTs) are increasingly used when randomized controls are infeasible, unethical, or insufficient, including applications in rare diseases, oncology, pediatrics, and post-approval effectiveness research. Although…
A Real-World Evidence (RWE) Scientific Working Group (SWG) of the American Statistical Association Biopharmaceutical Section (ASA BIOP) has been reviewing statistical considerations for the generation of RWE to support regulatory…
PURPOSE Providing rapid answers and early acces to patients to innovative treatments without randomized clinical trial (RCT) is growing, with benefit estimated from single-arm trials. This has become common in oncology, impacting the…
In the last two decades, single-arm trials (SATs) have been effectively used to study anticancer therapies in well-defined patient populations using durable response rates as an objective and interpretable clinical endpoints. With a growing…
The ICH E9(R1) addendum provides guidelines on accounting for intercurrent events in clinical trials using the estimands framework. However, there has been limited attention to the estimands framework for meta-analysis. Using treatment…
The target trial framework enables causal inference from longitudinal observational data by emulating randomized trials initiated at multiple time points. Precision is often improved by pooling information across trials, with standard…
Causal inference is the goal of randomized trials and many observational studies. The first step in a formal causal inference framework is to define the causal estimand, and in both types of study this can be intuitively defined as the…
The estimand framework included in the addendum to the ICH E9 guideline facilitates discussions to ensure alignment between the key question of interest, the analysis, and interpretation. Therapeutic knowledge and drug mechanism play a…
Randomised controlled trials (RCTs) are regarded as the gold standard for estimating causal treatment effects on health outcomes. However, RCTs are not always feasible, because of time, budget or ethical constraints. Observational data such…
To precisely define the treatment effect of interest in a clinical trial, the ICH E9 estimand addendum describes that relevant so-called intercurrent events should be identified and strategies specified to deal with them. Handling…
Platform trials are multi-arm designs that simultaneously evaluate multiple treatments for a single disease within the same overall trial structure. Unlike traditional randomized controlled trials, they allow treatment arms to enter and…
Augmenting randomized controlled trials (RCTs) with external real-world data (RWD) has the potential to improve the finite sample efficiency of treatment effect estimators. We describe using adaptive targeted maximum likelihood estimation…
Confounding is a significant obstacle to unbiased estimation of causal effects from observational data. For settings with high-dimensional covariates -- such as text data, genomics, or the behavioral social sciences -- researchers have…
Confusion often arises when attempting to articulate target estimand(s) of a clinical trial in plain language. We aim to rectify this confusion by using a type of causal graph called the Single-World Intervention Graph (SWIG) to provide a…