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Discrete sequential boundaries for clinical trials
Abstract
Pocock (1977), O'Brien & Fleming (1979) and Slud & Wei (1982) have proposed different methods to construct discrete sequential boundaries for clinical trials. These methods require that the total number of decision times be specified in advance. In the present paper, we propose a more flexible way to construct discrete sequential boundaries. The method is based on the choice of a function, α*(t), which characterizes the rate at which the error level α is spent. The boundary at a decision time is determined by α*(t), and by past and current decision times, but does not depend on the future decision times or the total number of decision times.
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“Sequential testing methods, such as Group Sequential Testing (GST) (Jennison and Turnbull, 1999a; Lan and DeMets, 1983; Pocock, 1977; O'Brien and Fleming, 1979) and the Sequential Probability Ratio Test (SPRT) (Wald, 1945c), have long been used to optimize sample size and decision-making in various fields (e.g. clinical trials), by evaluating data at interim points.”
From Stop Guessing When to Stop Testing: Efficient Model Evaluation with Just Enough Data (2026) · cites this paper as Lan and DeMets, 1983
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A Multiple Testing Procedure for Clinical Trials
O'Brien, P. C., & Fleming, T. R. (1979) · Biometrics · doi:10.2307/2530245 · Cited by 3,311
Group sequential methods in the design and analysis of clinical trials
POCOCK, S. J. (1977) · Biometrika · doi:10.1093/biomet/64.2.191 · Cited by 1,831
Repeated Significance Tests on Accumulating Data
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Stochastically curtailed tests in long–term clinical trials
Lan, K. K. G., Simon, R. M., & Halperin, M. (1982) · Sequential Analysis · doi:10.1080/07474948208836014 · Cited by 356
Interim Analyses for Randomized Clinical Trials: The Group Sequential Approach
Pocock, S. (1982) · Biometrics · doi:10.2307/2530298 · Cited by 265
Two-Sample Repeated Significance Tests Based on the Modified Wilcoxon Statistic
SLUD, E. V., & Wei, L. (1982) · Journal of the American Statistical Association · doi:10.1080/01621459.1982.10477899 · Cited by 244
Crossing probabilities for a square root boundary by a bessel process
Long, D. M. D. (1981) · Communication in Statistics- Theory and Methods · doi:10.1080/03610928108828182 · Cited by 135
Sequential Testing of the Equality of Two Survival Distributions Using the Modified Savage Statistic
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A two sample wilcoxon test for progressively censored data
DAVIS, C. E. (1978) · Communication in Statistics- Theory and Methods · doi:10.1080/03610927808827630 · Cited by 23
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Majumdar, H., & Sen, P. K. (1977) · Communication in Statistics- Theory and Methods · doi:10.1080/03610927708827511 · Cited by 9
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Metadata
- Authors
- GORDON LAN, K. K., & DEMETS, D. L.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- Biometrika
- Publisher
- Oxford University Press (OUP)
- Published
- 1983
- Volume
- 70
- Issue
- 3
- Pages
- 659-663
- ISSN
- 0006-3444 (ISSN-L)
- 1464-3510
- OpenAlex
- W1990639292
- Cited by
- 2,310
- References
- 10
- Citations by year
- 2026: 51 · 2025: 69 · 2024: 80 · 2023: 78 · 2022: 63 · 2021: 73 · 2020: 77 · 2019: 96 · 2018: 76 · 2017: 89 · 2016: 90 · 2015: 72 · 2014: 112 · 2013: 73 · 2012: 101
- FWCI
- 7.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biometrika (publishedVersion)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Probability and Statistical Research
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- clinical trials, early stopping, alpha spending functions, sequential analysis, decision time, error rate control
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