Skip to main content

Advertisement

Level of evidence for promising subgroup findings in a negative trial

Article metrics

In drug development and drug licensing, it sometimes occurs that a new drug did not demonstrate effectiveness for the full study population, but there appears to be benefit in a relevant subgroup. This raises the question how strong the evidence from such a subgroup is in this situation, and which confirmatory testing strategies are the most appropriate.

Using simulation studies, we compared the evolution of the type I error rate and the power of several types of confirmatory strategies, including replications of subgroup findings in parallel or new studies. The primary outcome was assumed to be continuous and normally distributed.

In case of a single trial, the inflation of the overall type I error is substantial, especially in relatively small subgroups with the added risk of starting a replication trial that should not be done. When the p-value for the subgroup of interest is very small, i.e. below 0.001, the strength of evidence is improved but such a strong result is not likely to occur in case of an overall non-significant result. The level of evidence improves as expected when subgroup findings are replicated in (the design of) a new trial. In this situation, the overall type I error is very close to the theoretical value, and almost guarantees its control.

Author information

Correspondence to Julien Tanniou.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and Permissions

About this article

Cite this article

Tanniou, J., van der Tweel, I. & Roes, K. Level of evidence for promising subgroup findings in a negative trial. Trials 14, O105 (2013) doi:10.1186/1745-6215-14-S1-O105

Download citation

Keywords

  • Public Health
  • Error Rate
  • Primary Outcome
  • Simulation Study
  • Drug Development

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Please note that comments may be removed without notice if they are flagged by another user or do not comply with our community guidelines.