ArticlePloS one2025
Randomization in clinical trials with small sample sizes using group sequential designs.
Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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
1 citing paper in PubMed.
- Randomization in clinical trials with small sample sizes using group sequential designs.PloS one · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGroup sequential designs, which allow early stopping for efficacy or futility, may benefit from balanced sample sizes at interim and final analyses. This requirement for balance limits the choice of admissible randomization procedures. We investigate if the choice of randomization procedure, whether balanced or not, impacts the type I error probability and power in small sample clinical trials with group sequential designs.
methodsWe start with a literature review to assess how randomization procedures are reported in group sequential trials. We then investigate the impact of randomization procedures on the type I error probability and power of trials with Pocock, O'Brien-Fleming, Lan-DeMets and inverse normal combination test designs.
resultsOur findings show that only a limited number of published group sequential trials report sufficient randomization details. Simulation results demonstrate that deficiencies in the implementation of randomization can inflate type I error rates. Some combinations of group sequential designs and randomization procedures cause a loss of power, for example, when using inverse normal combination tests. When the planned balanced allocation ratio in (interim) analyses cannot be ensured, the Lan-DeMets approach is preferable for small sample trials due to its robustness to deviations between the planned and observed allocation ratio. The inverse normal combination test, while useful in trials with limited prior information, should be used cautiously with permuted block randomization that maintains the planned allocation ratio to avoid power loss.
conclusionWe propose a framework for selecting the most suitable combinations of group sequential design and randomization procedure for small sample clinical trials. Our findings highlight the need for improved reporting of randomization methods in group sequential clinical trials. Further, the validity of some of the group sequential designs relies on the application of appropriate randomization procedures which were difficult to identify in the literature and is possibly violated.
Indexed as
Identifiers
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.