Faculty, Staff and Student Publications
Publication Date
11-1-2024
Journal
BMC Medical Research Methodology
Abstract
BACKGROUND: The use of historical external control data in clinical trials has grown in interest and needs when considering the design of future trials. Hybrid control designs can be more efficient to achieve the same power with fewer patients and limited resources. The literature is sparse on appropriate statistical methods which can account for the differences between historical external controls and the control patients in a study. In this article, we illustrate the analysis framework of a clinical trial if a hybrid control design was used after determining an RCT may not be feasible.
METHODS: We utilize two previously completed RCTs in nonsquamous NSCLC and a nationwide electronic health record derived de-identified database as examples and compare 5 analysis methods on each trial, as well as a set of simulations to determine operating characteristics of such designs.
RESULTS: In single trial estimation, the Case Weighted Adaptive Power Prior provided estimated treatment hazard ratios consistent with the original trial's conclusions with narrower confidence intervals. The simulation studies showed that the Case Weighted Adaptive Power Prior achieved the highest power (and well controlled type-1 error) across all 5 methods with consistent study sample size.
CONCLUSIONS: By following the proposed hybrid control framework, one can design a hybrid control trial transparently and accounting for differences between control groups while controlling type-1 error and still achieving efficiency gains from the additional contribution from external controls.
Keywords
Randomized Controlled Trials as Topic, Research Design, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Electronic Health Records, Computer Simulation, Control Groups, Humans, Male, Female
DOI
10.1186/s12874-024-02383-3
PMID
39487399
PMCID
PMC11529009
PubMedCentral® Posted Date
11-1-2024
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
