scholarly journals Adverse Event Burden Score—A Versatile Summary Measure for Cancer Clinical Trials

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3251
Author(s):  
Jennifer G. Le-Rademacher ◽  
Shauna Hillman ◽  
Elizabeth Storrick ◽  
Michelle R. Mahoney ◽  
Peter F. Thall ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Treatment Cycle ◽  
Controlled Trials ◽  
Cancer Clinical Trials ◽  
Weighted Sum ◽  
Summary Measure ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Over Time

This article introduces the adverse event (AE) burden score. The AE burden by treatment cycle is a weighted sum of all grades and AEs that the patient experienced in a cycle. The overall AE burden score is the total AE burden the patient experienced across all treatment cycles. AE data from two completed Alliance multi-center randomized double-blind placebo-controlled trials, with different AE profiles (NCCTG 97-24-51: 176 patients, and A091105: 83 patients), were utilized for illustration. Results of the AE burden score analyses corroborated the trials’ primary results. In 97-24-51, the overall AE burden for patients on the treatment arm was 2.2 points higher than those on the placebo arm, with a higher AE burden for patients who went off treatment early due to AE. Similarly, in A091105, the overall AE burden was 1.6 points higher on the treatment arm. On the placebo arms, the AE burden in 97-24-51 remained constant over time; and increased in later cycles in A091105, likely attributable to the increase in disease morbidity. The AE burden score enables statistical comparisons analogous to other quantitative endpoints in clinical trials, and can readily accommodate different trial settings, diseases, and treatments, with diverse AE profiles.

Papers of note in Science Translational Medicine

2016 ◽  
Vol 9 (411) ◽  
pp. ec13-ec13
Author(s):  
Nancy R. Gough
Keyword(s):  
Clinical Trials ◽  
Food Allergy ◽  
Fragile X Syndrome ◽  
Neurodevelopmental Disorders ◽  
Translational Medicine ◽  
Fragile X ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Link Type

ImmunodeficiencySAPping immunopathologyDGKα inhibition restores apoptosis in SAP-deficient lymphocytes, decreasing immunopathology in XLP-1 patients.E. Ruffo, V. Malacarne, S. E. Larsen, R. Das, L. Patrussi, C. Wülfing, C. Biskup, S. M. Kapnick, K. Verbist, P. Tedrick, P. L. Schwartzberg, C. T. Baldari, I. Rubio, K. E. Nichols, A. L. Snow, G. Baldanzi, A. Graziani, Inhibition of diacylglycerol kinase α restores restimulation-induced cell death and reduces immunopathology in XLP-1. Sci. Transl. Med.8, 321ra7 (2016). [Abstract]AllergyFighting food allergyInfants who develop food allergy display hyperresponsive innate immunity at birth that promotes nonclassical TH2 differentiation.Y. Zhang, F. Collier, G. Naselli, R. Saffery, M. L. K. Tang, K. J. Allan, A.-L. Ponsonby, L. C. Harrison, P. Vuillermin, on behalf of the BIS Investigator Group, Cord blood monocyte–derived inflammatory cytokines suppress IL-2 and induce nonclassic “TH2-type” immunity associated with development of food allergy. Sci. Transl. Med.8, 321ra8 (2016). [Abstract]Fragile X SyndromeThe mGluR theory of fragile X, put to the testIn contrast to previous studies, targeting the mGluR pathway in fragile X syndrome patients did not improve behavior independent of FMR1 methylation.E. Berry-Kravis, V. Des Portes, R. Hagerman, S. Jacquemont, P. Charles, J. Visootsak, M. Brinkman, K. Rerat, B. Koumaras, L. Zhu, G. M. Barth, T. Jaecklin, G. Apostol, F. von Raison, Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials. Sci. Transl. Med.8, 321ra5 (2016). [Abstract]S. S. Jeste, D. H. Geschwind, Clinical trials for neurodevelopmental disorders: At a therapeutic frontier. Sci. Transl. Med.8, 321fs1 (2016). [Abstract]

The Effect of Desmopressin on Reducing Blood Loss in Cardiac Surgery – A Meta-Analysis of Double-Blind, Placebo-Controlled Trials

1995 ◽  
Vol 74 (04) ◽  
pp. 1064-1070 ◽  
Author(s):  
Marco Cattaneo ◽  
Alan S Harris ◽  
Ulf Strömberg ◽  
Pier Mannuccio Mannucci
Keyword(s):  
Cardiac Surgery ◽  
Blood Loss ◽  
Meta Analysis ◽  
Postoperative Blood Loss ◽  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Transfusion Requirements ◽  
The Mean ◽  
Excessive Blood Loss

SummaryThe effect of desmopressin (DDAVP) on reducing postoperative blood loss after cardiac surgery has been studied in several randomized clinical trials, with conflicting outcomes. Since most trials had insufficient statistical power to detect true differences in blood loss, we performed a meta-analysis of data from relevant studies. Seventeen randomized, double-blind, placebo-controlled trials were analyzed, which included 1171 patients undergoing cardiac surgery for various indications; 579 of them were treated with desmopressin and 592 with placebo. Efficacy parameters were blood loss volumes and transfusion requirements. Desmopressin significantly reduced postoperative blood loss by 9%, but had no statistically significant effect on transfusion requirements. A subanalysis revealed that desmopressin had no protective effects in trials in which the mean blood loss in placebo-treated patients fell in the lower and middle thirds of distribution of blood losses (687-1108 ml/24 h). In contrast, in trials in which the mean blood loss in placebo-treated patients fell in the upper third of distribution (>1109 ml/24 h), desmopressin significantly decreased postoperative blood loss by 34%. Insufficient data were available to perform a sub-analysis on transfusion requirements. Therefore, desmopressin significantly reduces blood loss only in cardiac operations which induce excessive blood loss. Further studies are called to validate the results of this meta-analysis and to identify predictors of excessive blood loss after cardiac surgery.

scholarly journals Impact of maternal supplementation with probiotics during pregnancy on atopic eczema in childhood – a meta-analysis

2011 ◽  
Vol 107 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Katja Doege ◽  
Donata Grajecki ◽  
Birgit-Christiane Zyriax ◽  
Elena Detinkina ◽  
Christine zu Eulenburg ◽  
...  
Keyword(s):  
Atopic Eczema ◽  
Data Extraction ◽  
Meta Analysis ◽  
Significant Risk ◽  
Controlled Trials ◽  
Bacterial Strains ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Study Selection ◽  
The Impact

In the present study, we sought to conduct a literature review of randomised, double-blind, placebo-controlled trials, which assessed the impact of probiotics intake during pregnancy on the development of eczema in children. A meta-analysis was conducted for comparison of the development of atopic eczema in children whose mothers took probiotics during pregnancyv.placebo. Study selection, quality appraisal and data extraction were performed independently and in duplicate. The studies were rated according to their size in order to calculate the influence of individual studies on the meta-analysis. A total of seven randomised, double-blind, placebo-controlled trials, published between 2001 and 2009, were selected from the PubMed and Ovid databases for the meta-analysis. The meta-analysis was performed with statistical software Stata/SE11.0. The completed meta-analysis of the seven studies shows a significant risk reduction for atopic eczema in children aged 2–7 years by the administration of probiotics during pregnancy (reduction 5·7 %;P = 0·022). However, this effect was only significant for lactobacilli (reduction 10·6 %;P = 0·045), but not for a mixture of various bacterial strains as probiotics (difference 3·06 %,P = 0·204). In conclusion, the meta-analysis shows that the administration of lactobacilli during pregnancy prevents atopic eczema in children aged from 2 to 7 years. However, a mixture of various bacterial strains does not affect the development of atopic eczema, independent of whether they contain lactobacilli or not.

scholarly journals Cardiovascular Profile of Valbenazine: Analysis of Pooled Data from Three Randomized, Double-Blind, Placebo-Controlled Trials

Drug Safety ◽  
2017 ◽  
Vol 41 (4) ◽  
pp. 429-440 ◽  
Author(s):  
Dao Thai-Cuarto ◽  
Christopher F. O’Brien ◽  
Roland Jimenez ◽  
Grace S. Liang ◽  
Joshua Burke
Keyword(s):  
Controlled Trials ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Pooled Data ◽  
Cardiovascular Profile

Limitations of the Hazard Ratio as a Summary Measure in Cancer Clinical Trials

2021 ◽  
Vol 16 (10) ◽  
pp. e86-e87
Author(s):  
Quynh-Lan Dao ◽  
Quan Phung ◽  
Michael A. Liu
Keyword(s):  
Clinical Trials ◽  
Hazard Ratio ◽  
Cancer Clinical Trials ◽  
Summary Measure

scholarly journals 902. A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy of a Single Immunization of Ad26.RSV.preF against RSV Infection in a Viral Challenge Model in Healthy Adults

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S27-S28 ◽  
Author(s):  
John DeVincenzo ◽  
Efi Gymnopoulou ◽  
Els De Paepe ◽  
Bryan Murray ◽  
Arangassery Rosemary Bastian ◽  
...  
Keyword(s):  
Disease Severity ◽  
Healthy Adults ◽  
Controlled Study ◽  
Clinical Strain ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Qrt Pcr ◽  
Rsv Infection ◽  
First Time ◽  
Over Time

Abstract Background Despite the high disease burden of RSV in older adults and children, there is currently no approved vaccine. Ad26.RSV.preF, an experimental RSV vaccine, has demonstrated immunogenicity and tolerability in first-in-human clinical studies. The aim of this study was to assess the potential of the Ad26.RSV.preF vaccine to protect against RSV infection and disease in an established RSV human challenge model, used for the first time to evaluate a vaccine. Methods We conducted a randomized, double-blind, placebo-controlled, human challenge study (NCT03334695). Healthy adults received 1 × 1011 vp Ad26.RSV.preF vaccine (active) or placebo (pbo) intramuscularly. After 28 days, volunteers were challenged intranasally with a low-passage clinical strain of RSV-A (0.8 mL of Memphis 37b) and then quarantined for 12 days. Nasal washes were collected twice daily throughout quarantine, starting 2 days post-challenge (viral load [VL] by qRT-PCR and quantitative cultures). Disease severity was recorded thrice daily using symptom diary cards. Results Fifty-three volunteers (active, n = 27; pbo, n = 26) were challenged with RSV-A. Quantitative viral assessments were consistently lower in active than pbo. The primary endpoint of the study was met: the area under the curve (AUC) for RSV VL over time (via qRT-PCR) was significantly lower in active pbo (P = 0.012). Median peak VL was lower for active (0 log10 copies/mL) than pbo (5.4 log10 copies/mL). Median AUC for RSV VL over time (quantitative culture) was lower for active than pbo (0 vs. 109, P = 0.002). Disease severity was lower for active than pbo, with a median AUC total symptom score of 35 (active) vs. 167 (pbo) (P = 0.002). Overall, RSV infection (defined by qRT-PCR alone or combined with symptoms) and disease severity over time were lower in active vs. pbo. Conclusion RSV infections, VL, and RSV disease severity were consistently lower in healthy adults receiving Ad26.RSV.preF vs. placebo, demonstrating promising protection from RSV infection and disease. This was the first time that antiviral prevention was observed against RSV after active immunization. Ad26.RSV.preF warrants further evaluation in field trials for efficacy against natural RSV infections in populations considered at risk of severe RSV disease. Disclosures All Authors: No reported Disclosures.

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