Trial reportPloS one2024
Methodological insights from the EPISTOP trial to designing clinical trials in rare diseases-A secondary analysis of a randomized clinical trial.
Trial report in PloS one, 2024. 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
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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.
- Does randomization matter in rare disease clinical trials.PloS one · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn clinical research, the most appropriate way to assess the effect of an intervention is to conduct a randomized controlled trial (RCT). In the field of rare diseases, conducting an RCT is challenging, resulting in a low rate of clinical trials, with a high frequency of early termination and unpublished trials. The aim of the EPISTOP trial was to compare outcomes in infants with tuberous sclerosis (TSC) who received vigabatrin preventively before the seizures onset with those who received it conventionally after. The study was designed as a prospective, multicentre, randomized clinical trial. However, ethics committees at four centres did not approve this RCT design, resulting in an open-label trial (OLT) in these four centres and an RCT in the other six centres. In this paper, we re-analyse the data from the EPISTOP trial using methods to investigate the influence of allocation bias on the results of the EPISTOP trial.
methodA bias-corrected analysis is used to support and strengthen the published results. We included a term representing the effect of selection bias as an influencing factor on the corresponding endpoint in the statistical model. Thus, the treatment effect estimates for the primary endpoint of time to first seizure and additional secondary endpoints are adjusted for the bias effect.
resultThe bias-corrected analyses for the primary endpoint show that the estimated hazard ratio and associated confidence intervals are in a very similar range (original analysis: HR 2.91, 95%-CI [1.11 to 7.67], p-value 0.0306; bias-corrected analysis: HR 2.89, 95%-CI [1.10 to 7.58], p-value 0.0316). This was also the case for the secondary endpoints.
conclusionThe statistical re-analysis of the raw trial data therefore supports the published results and confirms that there is no additional bias introduced by randomization, thereby increasing the value of the results. However, this highlights that this aspect needs to be considered in future trials, especially in rare diseases, to avoid additional biases in an already small sample size where it may be difficult to reach significance.
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