Related papers: A Surrogate Endpoint Based Provisional Approval Ca…

There are many scenarios where short- and long-term causal effects of an intervention are different. For example, low-quality ads may increase short-term ad clicks but decrease the long-term revenue via reduced clicks. This work, therefore,…

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their…

Identification of causal effects is one of the most fundamental tasks of causal inference. We consider an identifiability problem where some experimental and observational data are available but neither data alone is sufficient for the…

Inferring causal effects on long-term outcomes using short-term surrogates is crucial to rapid innovation. However, even when treatments are randomized and surrogates fully mediate their effect on outcomes, it's possible that we get the…

When the primary outcome is hard to collect, surrogate endpoint is typically used as a substitute. However, even when the treatment has a positive average causal effect (ACE) on the surrogate endpoint, which also has a positive ACE on the…

Surrogate endpoints are often used in place of expensive, delayed, or rare true endpoints in clinical trials. However, regulatory authorities require thorough evaluation to accept these surrogate endpoints as reliable substitutes. One…

Estimating long-term causal effects based on short-term surrogates is a significant but challenging problem in many real-world applications, e.g., marketing and medicine. Despite its success in certain domains, most existing methods…

When direct measurement of a clinically relevant primary endpoint in a clinical trial is infeasible, a surrogate endpoint may be used instead to infer treatment effects. Trial-level surrogates predict the average treatment effect on the…

In many empirical settings, directly observing a treatment variable may be infeasible although an error-prone surrogate measurement of the latter will often be available. Causal inference based solely on the surrogate measurement is…

When the primary outcome is difficult to collect, surrogate endpoint is typically used as a substitute. It is possible that for every individual, treatment has a positive effect on surrogate, and surrogate has a positive effect on primary…

Principal stratification is a causal framework to analyze randomized experiments with a post-treatment variable between the treatment and endpoint variables. Because the principal strata defined by the potential outcomes of the…

In oncology, phase II or multiple expansion cohort trials are crucial for clinical development plans. This is because they aid in identifying potent agents with sufficient activity to continue development and confirm the proof of concept.…

Delayed primary outcomes and administratively censored follow-up create a general semiparametric estimation problem: the target causal functional depends on an endpoint observed only for a shrinking subset of units at analysis time, while…

Purpose: The Targeted Learning roadmap provides a systematic guide for generating and evaluating real-world evidence (RWE). From a regulatory perspective, RWE arises from diverse sources such as randomized controlled trials that make use of…

Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…

Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious…

Introduction: Increasing interest in real-world evidence has fueled the development of study designs incorporating real-world data (RWD). Using the Causal Roadmap, we specify three designs to evaluate the difference in risk of major adverse…

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…

Objectives: Surrogate endpoints, used to substitute for and predict final clinical outcomes, are increasingly being used to support submissions to health technology assessment agencies. The increase in use of surrogate endpoints has been…

We study target-population distributional and quantile treatment effects when a source study observes treatment and post-treatment surrogates for all source units but observes a long-run primary outcome only for a validation subset, while…