Using Marginal Structural Models to analyze Randomized Clinical Trials with non-adherence and lost to follow up

2021 ◽  
Author(s):  
Elizabeth A. Lancet ◽  
Luisa N. Borrell ◽  
Janet Holbrook ◽  
Alfredo Morabia
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Structural Models ◽  
Marginal Structural Models ◽  
Lost To Follow Up

Lost to Follow-up and Withdrawal of Consent in Contemporary Global Cardiovascular Randomized Clinical Trials

2015 ◽  
Vol 14 (4) ◽  
pp. 150-153 ◽  
Author(s):  
Fatima Rodriguez ◽  
Robert W. Harrison ◽  
Daniel Wojdyla ◽  
Kenneth W. Mahaffey
Keyword(s):  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Lost To Follow Up

Abstract P476: Safety and Efficacy of Balloon Mounted Drug-Eluting Stent in the Treatment of Symptomatic Intracranial Atherosclerotic Disease Multicenter International Experience

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Mahmoud Mohammaden ◽  
Raul G Nogueira ◽  
WONDWOSSEN TEKLE ◽  
farhan siddiq ◽  
Diogo C Haussen ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Endovascular Treatment ◽  
Medical Management ◽  
Randomized Clinical Trials ◽  
Atherosclerotic Disease ◽  
Drug Eluting Stent ◽  
Safety And Efficacy ◽  
Intracranial Atherosclerotic Disease ◽  
Drug Eluting

Introduction: Intracranial atherosclerotic disease (ICAD) is a common cause of refractory stroke. Randomized clinical trials failed to prove the safety and efficacy of the endovascular treatment options of symptomatic ICAD (sICAD). However, there are many concerns regarding inclusion criteria in these trials which made them less effective than standard medical management. Herein, we aim to study the safety and efficacy of drug-eluting balloon mounted stents (DES) in the treatment of sICAD. Methods: A retrospective review of endovascular database from 10 comprehensive stroke centers inside and outside the USA from January 2017 to January 2020 was reviewed. Patients were included if they had symptomatic intracranial stenosis ≥70% in the target vessel, failed best medical management, and underwent intracranial stenting with DES. The primary outcome was the occurrence of ischemic stroke, hemorrhage, or mortality within 72 hours of the procedure. Secondary outcomes included rates of symptomatic and angiographic recurrence within 6 months of the procedure. Results: There was a total of 129 patients, the median age was 65 [58-72] years, 40 (31%) were females. The intracranial stenotic lesions were located in anterior circulation in 74 (57.4%) of cases [24 (18.6%) supraclinoid ICA, 5 (3.9%) cavernous ICA, 17 (13.2%) petrous ICA, 5 (19.4%) MCA-M1, and 3 (2.3%) M2] and in posterior circulation in 55 (42.6%) of cases [36 (27.9) vertebral artery V4 segment, 18 (14%) basilar and 1 (0.7%) PCA]. Recurrent stroke was the qualifying event in 101 (78.3%) while transient ischemic attacks (TIA) were identified in 28 (21.7%) of cases. The median time from the qualifying event to stenting was 6 [2-24] days. Strokes were reported within 72 hours of the procedure; 2 (1.6%) ischemic, 2 (1.6%) hemorrhagic strokes and 2 (1.6%) patients suffered inpatient mortality. The median follow-up time was 6 [3-6.75] months. Among 99 patients who had clinical follow up 2 (2%) had TIA and 6 (6.1%) had strokes. Fifty-one patients had follow-up imaging of whom symptomatic ISR was reported in 8 (15.7%). Conclusion: Our study has shown that in appropriately selected patients with sICAD, endovascular treatment using DES is safe and effective. Prospective randomized clinical trials are warranted.

Progression-free survival (PFS) as surrogate endpoint for overall survival (OS) in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer (MBC): An individual patient data (IPD) analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 610-610 ◽  
Author(s):  
Stefan Michiels ◽  
Lina Pugliano ◽  
Delphine Grun ◽  
Jana Barinoff ◽  
David A. Cameron ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Effects ◽  
Randomized Clinical Trials ◽  
Metastatic Breast ◽  
Targeted Agents ◽  
First Line ◽  
Her2 Positive ◽  
Individual Level ◽  
The Individual

610 Background: The gold standard endpoint in randomized clinical trials (RCTs) in MBC is OS, which has the disadvantage of requiring extended follow-up and being confounded by subsequent anti-cancer therapies. Although therapeutics have been approved based on PFS, its use as a primary endpoint is controversial. This study, the first IPD meta-analysis of targeted agents in MBC, aimed to collect data from RCTs of HER2-targeted agents in HER2+ MBC, assessing to what extent PFS correlates with, and may be used as, a surrogate for OS. Methods: A search was conducted in April 2011. Eligible RCTs accrued HER2+ MBC patients (pts) in 1992-2008. Collaboration was obtained from industrial partners (Roche, GSK) for industry-led studies. Investigator-assessed PFS was defined as the time from randomization to clinical or radiological progression, or death. A correlation approach was used: at the individual level, to estimate the association between PFS and OS using a bivariate survival model and at the trial level, to estimate the association between treatment effects on PFS and OS. Squared correlation values close to 1.0 would indicate strong surrogacy. Results: The search strategy resulted in 2137 eligible pts in 13 RCTs testing trastuzumab or lapatinib. We collected IPD data from 1963 pts in 9 RCTs. One phase II RCT did not have sufficient follow-up data so that 1839 pts in 8 RCTs were retained (5 evaluating trastuzumab, 3 lapatinib); 6 out of 8 RCTs were first-line. At the individual level, the Spearman rank correlation using Hougaard copula was equal to r=0.66 (95% CI 0.65 to 0.66) corresponding to an r2 of 0.42. At the trial level, the squared correlation between treatment effects on PFS and OS was provided by R2=0.33 (95% CI -0.22 to 0.86) using Hougaard copula and R2=0.53 (95% CI 0.22 to 0.83) using log hazard ratios from Cox models. Conclusions: In RCTs of HER2-targeted agents in HER2+ MBC, PFS is moderately correlated with OS and treatment effects on PFS are modestly correlated with treatment effects on OS, similarly to first-line chemotherapy in MBC (Burzykowski et al JCO 2008). PFS does not completely substitute for OS.

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