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 language | English (US) |
|---|---|
| Pages (from-to) | 344-358 |
| Number of pages | 15 |
| Journal | Journal of Biopharmaceutical Statistics |
| Volume | 24 |
| Issue number | 2 |
| DOIs | |
| State | Published - Mar 4 2014 |
Bibliographical note
Funding Information:This work was supported in part by grant 1UL1RR033183 from the National Center for Research Resources and by grant 8 UL1 TR000114-02 from the National Center for Advancing Translational Sciences of the National Institutes of Health.
Keywords
- Biomarker
- Clinical trial design
- Enrichment
- Heterogeneous effects
- Operating characteristics
- Sample size