ReviewStatistics in medicine2023
Point estimation for adaptive trial designs I: A methodological review.
Review in Statistics in medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Confidence Intervals for Adaptive Trial Designs I: A Methodological Review.Statistics in medicine · 2025Pooled it
- Rejoinder: "Adaptive versus fixed designs in confirmatory clinical trials: Centering the choice on ethics".Clinical trials (London, England) · 2026Article
- Design, simulate, refine: simulation-guided clinical trials for accelerated drug development.Nature reviews. Drug discovery · 2026Review
- Adaptive versus fixed designs in confirmatory clinical trials: centering the choice on ethics.Clinical trials (London, England) · 2026Article
- Conditional Estimations for Seamless Phase II/III Clinical Trials Involving Multi-Stage Early Stopping.Statistics in medicine · 2026Article
- A visual framework for classifying adaptive design clinical trials using the GATE frame and PICO terminology.Dialogues in health · 2026Review
- On the Inclusion of Non-Concurrent Controls in Platform Trials With an Interim Analysis.Statistics in medicine · 2026Article
- Confidence intervals and point estimates for treatment effects in adaptive enrichment designs.Statistical methods in medical research · 2026Article
- Clinical Trial Simulation: Planning With the OCTAVE Framework, Implementation and Validation Principles.Statistics in medicine · 2026Article
- Group-Sequential Designs With an Externally-Driven Change of Primary Endpoint.Statistics in medicine · 2025Article
- Inference in group sequential designs with causal mechanisms: implications for power and mediation analysis.BMC medical research methodology · 2025Article
- Practical guidance for conducting high-quality and rapid interim analyses in adaptive clinical trials.BMC medicine · 2025Review
- Response adaptive randomisation in clinical trials: Current practice, gaps and future directions.Statistical methods in medical research · 2025Article
- Confidence Intervals for Adaptive Trial Designs II: Case Study and Practical Guidance.Statistics in medicine · 2025Review
- Adjustment of Conditional Bias in Hazard Ratios for Group Sequential Testing of Progression-Free Survival and Overall Survival.Statistics in medicine · 2025Article
- Statistical Inference for a Two-Stage Adaptive Seamless Design Using Different Binary Endpoints.Statistics in medicine · 2025Article
- Past, present, and future of Phase 3 vaccine trial design: rethinking statistics for the 21st century.Clinical and experimental immunology · 2025Review
- Unmasking Racial, Ethnic, and Socioeconomic Disparities in United States Chordoma Clinical Trials: Systematic Review.Cancers · 2025Review
- Practical and analytical considerations when performing interim analyses in diagnostic test accuracy studies.Diagnostic and prognostic research · 2024Article
- The impact of heterogeneity on the analysis of platform trials with normally distributed outcomes.BMC medical research methodology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
Recent FDA guidance on adaptive clinical trial designs defines bias as "a systematic tendency for the estimate of treatment effect to deviate from its true value," and states that it is desirable to obtain and report estimates of treatment effects that reduce or remove this bias. The conventional end-of-trial point estimates of the treatment effects are prone to bias in many adaptive designs, because they do not take into account the potential and realized trial adaptations. While much of the methodological developments on adaptive designs have tended to focus on control of type I error rates and power considerations, in contrast the question of biased estimation has received relatively less attention. This article is the first in a two-part series that studies the issue of potential bias in point estimation for adaptive trials. Part I provides a comprehensive review of the methods to remove or reduce the potential bias in point estimation of treatment effects for adaptive designs, while part II illustrates how to implement these in practice and proposes a set of guidelines for trial statisticians. The methods reviewed in this article can be broadly classified into unbiased and bias-reduced estimation, and we also provide a classification of estimators by the type of adaptive design. We compare the proposed methods, highlight available software and code, and discuss potential methodological gaps in the literature.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.