Publication

Sequential designs for clinical trials in amyotrophic lateral sclerosis

Groeneveld, GJ., van der Tweel, N. V., Wokke, JHJ. & van den Berg, LH., Dec-2004, In : Amyotrophic lateral sclerosis and other motor neuron disorders. 5, 4, p. 202-207 6 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • GJ Groeneveld
  • [No Value] van der Tweel
  • JHJ Wokke
  • LH van den Berg

BACKGROUND: The objective of this paper is to discuss the sequential trial design and its advantages in clinical trials for ALS. The sequential trial design is an alternative to the classical trial design, which permits stopping a study as soon as a treatment effect can be significantly demonstrated or denied. METHODS: As an example of a sequential survival analysis, a recently completed clinical trial is described. A secondary outcome measure used in the same trial, the decline of the vital lung capacity, was re-analyzed sequentially, in order to illustrate the use of the sequential method for a non-survival variable. To compare the classical with the sequential trial design, the number of patients needed in trials aiming at survival effects ranging from 10% to 20% with a power of 80% or 90% was calculated for both designs. RESULTS: In the given examples the time needed to prove the null hypothesis in the survival analysis, and the number of patients needed to prove the null hypothesis in the analysis of the vital capacity is lower than would have been the case in a classical analysis. In 18 of 24 different situations, the chance is at least 90% that with a sequential trial design fewer patients are needed. CONCLUSIONS: We argue that, particularly for ALS trials, a sequential design may be superior to a classical trial design, as it most often requires fewer patients than classically designed trials of equal power, and more importantly may avoid unnecessary continuation.

Original languageEnglish
Pages (from-to)202-207
Number of pages6
JournalAmyotrophic lateral sclerosis and other motor neuron disorders
Volume5
Issue number4
Publication statusPublished - Dec-2004

    Keywords

  • amyotrophic lateral sclerosis, statistical analysis, trial design, CREATINE, RILUZOLE

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