scholarly journals Comparison of assessments by blinded independent central reviewers and local investigators: An analysis of phase III randomized control trials on solid cancers (2010-2015)

2016 ◽  
Vol 27 ◽  
pp. vi100
Author(s):  
W. Liang ◽  
J. Zhang ◽  
Q. He ◽  
S. Tang ◽  
Y. Zhang ◽  
...  
Keyword(s):  
Phase Iii ◽  
Randomized Control Trials ◽  
Randomized Control

Optimism bias in the design of phase III randomized control trials (RCTs) evaluating PD-1/PD-L1 targeting monoclonal antibodies (mAbs).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18616-e18616
Author(s):  
Laith Al-Showbaki ◽  
Fahad Almugbel ◽  
Husam Alqaisi ◽  
Eitan Amir ◽  
Eric Xueyu Chen
Keyword(s):  
Monoclonal Antibodies ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Randomized Control Trials ◽  
Optimism Bias ◽  
Number Of Patients ◽  
Cancer Types ◽  
The Mean ◽  
Randomized Control ◽  
Palliative Setting

e18616 Background: PD-1/PD-L1 targeting monoclonal antibodies (mAbs) improve outcomes in multiple cancer types. Multiple mAbs are in clinical development, and many randomized control trials (RCTs) have been completed or are in progress. These RCTs compete for limited clinical trials infrastructure, human resources and patients. Since the hypothesized benefit of an intervention is a critical determinant of the number of patients required for an RCT, it is crucial that the expected benefit be estimated appropriately. We examined the hypothesized hazard ratio (HHR) and the observed hazard ratio (OHR) in RCTs evaluating PD-1/PD-L1 targeting mAbs. Methods: Publications of RCTs evaluating at least one PD-1/PD-L1 targeting mAbs approved by the US Food and Drug Administration were identified through PubMed searches. The primary publication for each RCT and its associated protocol were retrieved. Two investigators independently extracted HHR, OHR for the primary endpoint among other data elements. The differences (∆HR) in HHR and OHR were analyzed statistically. Updated OHRs (uOHR) were extracted from reports with extended follow-ups. Results: 49 RCTs enrolling 36867 patients were included. 45/49 RCTs were in the palliative setting. HHR was met or exceeded in 22 (45%) RCTs. The mean HHR and OHR were 0.672 and 0.738, respectively. The mean ∆HR was 0.067 (range: -0.300 to 0.895, 95% confidence interval = 0.003 – 0.130). A lower magnitude of effect than hypothesized in 12/29 RCTs in non-small cell lung cancer, melanoma and renal cell carcinoma, but in 15/20 RCTs in other cancer types. OHR was ≥ 1.0 in 6 RCTs (12%). In the palliative setting, ∆HR was larger in more heavily pre-treated patients. PD-L1 expression was not associated with magnitude of effect. However, a higher magnitude of effect was observed for RCTs published in the New England Journal of Medicine. For 18 RCTs with extended follow-ups, uOHR was higher than OHR in 8. Conclusions: The majority of published RCTs evaluating PD-1/PD-L1 targeting mAbs did not achieve their hypothesized magnitude of effect. Investigators’ optimism regarding these agents should be combined with more realistic expectations. The optimism bias requires attention from the cancer clinical research community given the number of these agents in development and the intense interest in evaluating these agents in various disease settings.

EXPRESS: Comparison of Mothership versus Drip-and-Ship Models in treating patients with Acute Ischemic Stroke: A systematic review and meta-analysis

2021 ◽  
pp. 174749302110132
Author(s):  
Ahmed Mohamed ◽  
Nida Fatima ◽  
Ashfaq Shuaib ◽  
Maher Saqqur
Keyword(s):  
Functional Outcome ◽  
Meta Analysis ◽  
Critical Time ◽  
Functional Independence ◽  
Models Of Care ◽  
Randomized Control Trials ◽  
Symptomatic Intracerebral Hemorrhage ◽  
Significant Difference ◽  
The Mean ◽  
Randomized Control

Introduction There is controversy if direct to comprehensive center “mothership” (MS) or stopping at primary center for thrombolysis before transfer to comprehensive center “drip-and- ship” (DS) are best models of treatment of acute stroke. In this study, we compare MS and DS models to evaluate the best option of functional outcome. Methods Studies between 1990 and 2020 were extracted from online electronic databases. We compared the clinical outcomes, critical time measurements, functional independence and mortality were then compared. Results A total of 7,824 patients’ data were retrieved from 13 publications (3 randomized control trials and 10 retrospective ones). 4,639 (59.3%) patients were treated under MS model and 3,185 (40.7%) followed the DS model with mean age of 70.01±3.58 vs. 69.03±3.36; p< 0 .001, respectively. The National Institute Health Stroke Scale was 15.57±3.83 for the MS and 15.72±2.99 for the DS model (p=<0.001). The mean symptoms onset-to-puncture time was significantly shorter in the MS group compared to the DS (159.69 min vs. 223.89 min; p=<0.001, respectively). Moreover, the collected data indicated no significant difference between symptom’s onset to intravenous (IV) thrombolysis time and stroke onset-to-successful recanalization time (p=0.205 and p=<0.001, respectively). Patients had significantly worse functional outcome [modified rankin score (mRS)] (3-6) at 90-days in the DS model [Odds Ratio (OR): 1.47, 95% Confidence Interval (CI): 1.13-1.92, p<0.004] and 1.49-folds higher likelihood of symptomatic intracerebral hemorrhage (OR: 1.49, 95%CI: 1.22-1.81, p<0.0001) compared to MS. However, there were no statistically significant difference in terms of mortality (OR: 1.16, 95%CI: 0.87-1.55, p=0.32) and successful recanalization (OR: 1.12, 95%CI: 0.76-1.65, p=0.56) between the two models of care. Conclusion Patients in the MS model have significantly improved functional independence and recovery. Further studies are needed as the data from prospectively randomized studies is not of sufficient quality to make definite recommendations.

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