Unified exact design with early stopping rules for single arm clinical trials with multiple endpoints

Details

• Alternative Title:
  Stat Methods Med Res
• Personal Author:
  Wei, Wei ; Esserman, Denise ; Kane, Michael ; Zelterman, Daniel
• Description:
  Adaptive designs are gaining popularity in early phase clinical trials because they enable investigators to change the course of a study in response to accumulating data. We propose a novel design to simultaneously monitor several endpoints. These include efficacy, futility, toxicity and other outcomes in early phase, single-arm studies. We construct a recursive relationship to compute the exact probabilities of stopping for any combination of endpoints without the need for simulation, given pre-specified decision rules. The proposed design is flexible in the number and timing of interim analyses. A R Shiny app with user-friendly web interface has been created to facilitate the implementation of the proposed design.
• Subjects:
  Computer Simulation Medical Futility Probability Research Design
• Keywords:
  Biomarker Endpoints Conditional Power Early Phase Go/No Go Decisions Multiple Endpoints
• Source:
  Stat Methods Med Res. 30(7):1575-1588
• Pubmed ID:
  34159859
• Pubmed Central ID:
  PMC8959087
• Document Type:
  Journal Article
• Funding:
  R01 ES005775/ES/NIEHS NIH HHSUnited States/ ; UL1 TR001863/TR/NCATS NIH HHSUnited States/ ; U01 CA235747/CA/NCI NIH HHSUnited States/ ; U48 DP005023/DP/NCCDPHP CDC HHSUnited States/ ; P50 CA121974/CA/NCI NIH HHSUnited States/ ; R35 CA197574/CA/NCI NIH HHSUnited States/ ; R01 CA168733/CA/NCI NIH HHSUnited States/ ; P30 CA016359/CA/NCI NIH HHSUnited States/ ; R01 CA223481/CA/NCI NIH HHSUnited States/ ; P50 CA196530/CA/NCI NIH HHSUnited States/ ; P50 DE030707/DE/NIDCR NIH HHSUnited States/ ; R41 AI120546/AI/NIAID NIH HHSUnited States/ ; UM1 CA186689/CA/NCI NIH HHSUnited States/ ; R01 CA177719/CA/NCI NIH HHSUnited States/
• Volume:
  30
• Issue:
  7
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:017029e9296d0a5f3e681656246812f22c74fe78b5aeaa480429e487dbd60a14cb1e5b34e0f87a926df5b2c502dacd26fe1ca9b6e1f6a77db781dfdf39e7f6bd
• Download URL:
  https://stacks.cdc.gov/view/cdc/115771/cdc_115771_DS1.pdf
• File Type:
  [PDF - 1.12 MB ]