Related papers: Considerations for Master Protocols Using External…
With more and better clinical data being captured outside of clinical studies and greater data sharing of clinical studies, external controls may become a more attractive alternative to randomized clinical trials. Both industry and…
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…
The use of patient-level information from previous studies, registries, and other external datasets can support the analysis of single-arm and randomized controlled trials to evaluate and test experimental treatments. However, the…
A master protocol trial uses a single overarching protocol to test multiple therapies, often across several diseases or subtypes. Although such trials offer considerable flexibility and efficiency, their constrained and non-uniform…
Leveraging external controls -- relevant individual patient data under control from external trials or real-world data -- has the potential to reduce the cost of randomized controlled trials (RCTs) while increasing the proportion of trial…
Background: Drug development is often inefficient, costly and lengthy, yet it is essential for evaluating the safety and efficacy of new interventions. Compared with other disease areas, this is particularly true for Phase II / III cancer…
One approach for increasing the efficiency of randomized trials is the use of "external controls" -- individuals who received the control treatment studied in the trial during routine practice or in prior experimental studies. Existing…
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…
Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…
It is increasingly common to augment randomized controlled trial with external controls from observational data, to evaluate the treatment effect of an intervention. Traditional approaches to treatment effect estimation involve ambiguous…
Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells. Innovations in clinical trial design have followed with master protocols defined by…
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…
External controls from historical trials or observational data can augment randomized controlled trials when large-scale randomization is impractical or unethical, such as in drug evaluation for rare diseases. However, non-randomized…
There is a growing interest in the implementation of platform trials, which provide the flexibility to incorporate new treatment arms during the trial and the ability to halt treatments early based on lack of benefit or observed…
In situations where it is difficult to enroll patients in randomized controlled trials, external data can improve efficiency and feasibility. In such cases, adaptive trial designs could be used to decrease enrollment in the control arm of…
Hybrid randomized controlled trials (hybrid RCTs) integrate external control data, such as historical or concurrent data, with data from randomized trials. While numerous frequentist and Bayesian methods, such as the test-then-pool and…
External controls (ECs) from historical trials or real-world data have gained increasing attention as a way to augment hybrid and single-arm trials, especially when balanced randomization is infeasible. While most existing work has focused…
In oncology the efficacy of novel therapeutics often differs across patient subgroups, and these variations are difficult to predict during the initial phases of the drug development process. The relation between the power of randomized…
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…
Randomized controlled trials (RCTs) are widely regarded as the gold standard for causal inference in biomedical research. For instance, when estimating the average treatment effect on the treated (ATT), a doubly robust estimation procedure…