5 research outputs found
Case Weighted Power Priors For Hybrid Control analyses With Time-To-Event Data
We develop a method for hybrid analyses that uses external controls to augment internal control arms in randomized controlled trials (RCTs) where the degree of borrowing is determined based on similarity between RCT and external control patients to account for systematic differences (e.g., unmeasured confounders). The method represents a novel extension of the power prior where discounting weights are computed separately for each external control based on compatibility with the randomized control data. The discounting weights are determined using the predictive distribution for the external controls derived via the posterior distribution for time-to-event parameters estimated from the RCT. This method is applied using a proportional hazards regression model with piecewise constant baseline hazard. A simulation study and a real-data example are presented based on a completed trial in non-small cell lung cancer. It is shown that the case weighted power prior provides robust inference under various forms of incompatibility between the external controls and RCT population
Case Weighted Adaptive Power Priors for Hybrid Control Analyses with Time-to-Event Data
We develop a method for hybrid analyses that uses external controls to
augment internal control arms in randomized controlled trials (RCT) where the
degree of borrowing is determined based on similarity between RCT and external
control patients to account for systematic differences (e.g. unmeasured
confounders). The method represents a novel extension of the power prior where
discounting weights are computed separately for each external control based on
compatibility with the randomized control data. The discounting weights are
determined using the predictive distribution for the external controls derived
via the posterior distribution for time-to-event parameters estimated from the
RCT. This method is applied using a proportional hazards regression model with
piecewise constant baseline hazard. A simulation study and a real-data example
are presented based on a completed trial in non-small cell lung cancer. It is
shown that the case weighted adaptive power prior provides robust inference
under various forms of incompatibility between the external controls and RCT
population.Comment: 27 pages, 10 figure
Phase II, Randomized Trial Comparing Bevacizumab Plus Fluorouracil (FU)/Leucovorin (LV) With FU/LV Alone in Patients With Metastatic Colorectal Cancer
Hormone Receptor Status Does Not Affect the Clinical Benefit of Trastuzumab Therapy for Patients with Metastatic Breast Cancer
Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo
BACKGROUND:
Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated.
METHODS:
ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy.
RESULTS:
Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events.
CONCLUSION:
ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk