Related papers: Estimands in Real-World Evidence Studies
The American Statistical Association Biopharmaceutical Section (ASA BIOP) scientific working group on real-world evidence (RWE) has been making continuous, extended efforts towards a goal of supporting and advancing regulatory science with…
Increasing emphasis on the use of real-world evidence (RWE) to support clinical policy and regulatory decision-making has led to a proliferation of guidance, advice, and frameworks from regulatory agencies, academia, professional societies,…
Real-world data (RWD) and real-world evidence (RWE) have been increasingly used in medical product development and regulatory decision-making, especially for rare diseases. After outlining the challenges and possible strategies to address…
Intercurrent (post-treatment) events occur frequently in randomized trials, and investigators often express interest in treatment effects that suitably take account of these events. A naive conditioning on intercurrent events does not have…
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…
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…
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…
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…
Matching and weighting methods for observational studies involve the choice of an estimand, the causal effect with reference to a specific target population. Commonly used estimands include the average treatment effect in the treated (ATT),…
Single-arm trials (SATs) may be used to support regulatory submissions in settings where there is a high unmet medical need and highly promising early efficacy data undermine the equipoise needed for randomization. In this context,…
Developing drugs for rare diseases presents unique challenges from a statistical perspective. These challenges may include slowly progressive diseases with unmet medical needs, poorly understood natural history, small population size,…
The estimand framework proposed by ICH in 2017 has brought fundamental changes in the pharmaceutical industry. It clearly describes how a treatment effect in a clinical question should be precisely defined and estimated, through attributes…
Estimands can help to clarify the research questions being addressed in randomised trials. Because the choice of estimand can affect how relevant trial results are to patients and other stakeholders, such as clinicians or policymakers, it…
The ICH E9(R1) guideline presents a framework of estimand for clinical trials, proposes five strategies for handling intercurrent events (ICEs), and provides a comprehensive discussion and many real-life clinical examples for quantitative…
While randomized controlled trials (RCTs) are the gold-standard for establishing the efficacy and safety of a medical treatment, real-world evidence (RWE) generated from real-world data (RWD) has been vital in post-approval monitoring and…
The analysis of adverse events (AEs) is a key component in the assessment of a drug's safety profile. Inappropriate analysis methods may result in misleading conclusions about a therapy's safety and consequently its benefit-risk ratio. The…
The ICH E9 (R1) addendum on estimands, coupled with recent advancements in causal inference, has prompted a shift towards using model-free treatment effect estimands that are more closely aligned with the underlying scientific question.…
Randomized controlled trials (RCTs) have been the cornerstone of clinical evidence; however, their cost, duration, and restrictive eligibility criteria limit power and external validity. Studies using real-world data (RWD), historically…
Many research questions concern treatment effects on outcomes that can recur several times in the same individual. For example, medical researchers are interested in treatment effects on hospitalizations in heart failure patients and sports…
The estimand framework is increasingly established to pose research questions in confirmatory clinical trials. In evidence synthesis, the uptake of estimands has been modest, and the PICO (Population, Intervention, Comparator, Outcome)…