Sample size and screening size trade-off in the presence of subgroups with different expected treatment effects

Kyle Rudser, Edward Bendert, Joe Koopmeiners

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

When designing clinical trials, sometimes we may expect a larger treatment effect in one group while others exhibit an attenuated effect. In these settings there can be a trade-off between a smaller average treatment effect with broader enrollment criteria and a larger effect with restricted criteria but longer enrollment duration. Identification of subgroups will often use a clinical decision rule, for example, biomarker cutoff, but may be imprecise, that is, with sensitivity and specificity not simultaneously 100%. We evaluate the impact of including attenuated subgroups on design operating characteristics and illustrate scenarios where overall trial duration may be shorter by not being restrictive.

Original languageEnglish (US)
Pages (from-to)344-358
Number of pages15
JournalJournal of Biopharmaceutical Statistics
Volume24
Issue number2
DOIs
StatePublished - Mar 4 2014

Fingerprint

Treatment Effects
Sample Size
Screening
Biomarkers
Trade-offs
Average Treatment Effect
Clinical Trials
Subgroup
Sensitivity and Specificity
Operating Characteristics
Decision Rules
Specificity
Scenarios
Evaluate
Design

Keywords

  • Biomarker
  • Clinical trial design
  • Enrichment
  • Heterogeneous effects
  • Operating characteristics
  • Sample size

Cite this

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AB - When designing clinical trials, sometimes we may expect a larger treatment effect in one group while others exhibit an attenuated effect. In these settings there can be a trade-off between a smaller average treatment effect with broader enrollment criteria and a larger effect with restricted criteria but longer enrollment duration. Identification of subgroups will often use a clinical decision rule, for example, biomarker cutoff, but may be imprecise, that is, with sensitivity and specificity not simultaneously 100%. We evaluate the impact of including attenuated subgroups on design operating characteristics and illustrate scenarios where overall trial duration may be shorter by not being restrictive.

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KW - Operating characteristics

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