Improving the Capture of Adverse Event Data in Clinical Trials: The Role of the International Atomic Energy Agency

2007 ◽  
Vol 69 (4) ◽  
pp. 1218-1221 ◽  
Author(s):  
Susan E. Davidson ◽  
Andy Trotti ◽  
Özlem U. Ataman ◽  
Jinsil Seong ◽  
Fen Nee Lau ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
International Atomic Energy Agency ◽  
Atomic Energy ◽  
Event Data ◽  
Energy Agency ◽  
Adverse Event Data

scholarly journals A Bayesian meta-analytic approach for safety signal detection in randomized clinical trials

2017 ◽  
Vol 14 (2) ◽  
pp. 192-200 ◽  
Author(s):  
Motoi Odani ◽  
Satoru Fukimbara ◽  
Tosiya Sato
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Adverse Events ◽  
Hierarchical Structure ◽  
Meta Analysis ◽  
Event Data ◽  
Analysis Model ◽  
Exact Test ◽  
Adverse Event Data ◽  
Fisher’S Exact Test

Background/Aim: Meta-analyses are frequently performed on adverse event data and are primarily used for improving statistical power to detect safety signals. However, in the evaluation of drug safety for New Drug Applications, simple pooling of adverse event data from multiple clinical trials is still commonly used. We sought to propose a new Bayesian hierarchical meta-analytic approach based on consideration of a hierarchical structure of reported individual adverse event data from multiple randomized clinical trials. Methods: To develop our meta-analysis model, we extended an existing three-stage Bayesian hierarchical model by including an additional stage of the clinical trial level in the hierarchical model; this generated a four-stage Bayesian hierarchical model. We applied the proposed Bayesian meta-analysis models to published adverse event data from three premarketing randomized clinical trials of tadalafil and to a simulation study motivated by the case example to evaluate the characteristics of three alternative models. Results: Comparison of the results from the Bayesian meta-analysis model with those from Fisher’s exact test after simple pooling showed that 6 out of 10 adverse events were the same within a top 10 ranking of individual adverse events with regard to association with treatment. However, more individual adverse events were detected in the Bayesian meta-analysis model than in Fisher’s exact test under the body system “Musculoskeletal and connective tissue disorders.” Moreover, comparison of the overall trend of estimates between the Bayesian model and the standard approach (odds ratios after simple pooling methods) revealed that the posterior median odds ratios for the Bayesian model for most adverse events shrank toward values for no association. Based on the simulation results, the Bayesian meta-analysis model could balance the false detection rate and power to a better extent than Fisher’s exact test. For example, when the threshold value of the posterior probability for signal detection was set to 0.8, the false detection rate was 41% and power was 88% in the Bayesian meta-analysis model, whereas the false detection rate was 56% and power was 86% in Fisher’s exact test. Limitations: Adverse events under the same body system were not necessarily positively related when we used “system organ class” and “preferred term” in the Medical Dictionary for Regulatory Activities as a hierarchical structure of adverse events. For the Bayesian meta-analysis models to be effective, the validity of the hierarchical structure of adverse events and the grouping of adverse events are critical. Conclusion: Our proposed meta-analysis models considered trial effects to avoid confounding by trial and borrowed strength from both within and across body systems to obtain reasonable and stable estimates of an effect measure by considering a hierarchical structure of adverse events.

scholarly journals Response to radiological accidents: the role of the International Atomic Energy Agency

2001 ◽  
Vol 36 (4) ◽  
pp. 459-475 ◽  
Author(s):  
I. Turai ◽  
M. Crick ◽  
C. Nogueira de Oliveira ◽  
P. Ortiz-Lopez ◽  
A. Wrixon
Keyword(s):  
International Atomic Energy Agency ◽  
Atomic Energy ◽  
Energy Agency

Real-World Safety of Emicizumab: The First Interim Analysis of the European Haemophilia Safety Surveillance (EUHASS) Database

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 29-30
Author(s):  
Aijing Shang ◽  
Nives Selak Bienz ◽  
Ravi Gadiraju ◽  
Tiffany Chang ◽  
Peter Kuebler
Keyword(s):  
Clinical Trials ◽  
Adverse Event ◽  
Adverse Events ◽  
Real World ◽  
Event Data ◽  
Publicly Traded ◽  
Real World Data ◽  
World Data ◽  
Safety Surveillance ◽  
Adverse Event Data

Introduction: Long-term data from the HAVEN 1-4 clinical trials reaffirmed the safety and efficacy of emicizumab (HEMLIBRA®) prophylaxis in persons with hemophilia A (PwHA; Callaghan M et al. ISTH 2019 presentation). However, early data from the first Phase III trial, HAVEN 1, identified a risk for thrombotic microangiopathy (TMA) or thrombotic events (TEs) when emicizumab was used alongside activated prothrombin complex concentrate (aPCC [FEIBA]; dosed on average a cumulative amount of >100 U/kg/24 hours for ≥24 hours) leading to a warning in the label and ongoing safety monitoring. European Haemophilia Safety Surveillance (EUHASS) is a large pharmacovigilance program that monitors the safety of treatments for inherited bleeding disorders. The EUHASS registry includes real-world data on the use of emicizumab in a broad, representative population of PwHA. The objective of this analysis was to summarize thrombotic, TMA, and anaphylaxis events reported to EUHASS in association with emicizumab prophylaxis. Methods: EUHASS is an investigator-led program with 86 participating centers in 27 countries, with centers reporting information on all the individuals they treat, thus minimizing selection bias. Adverse event data were collected from all PwHA in EUHASS who received emicizumab prophylaxis during 2018. EUHASS adverse event data are not collected according to Medical Dictionary for Regulatory Affairs (MedDRA) classification; however, for this exploratory analysis, events were coded at MedDRA preferred term level as far as possible; endpoints are provided as descriptive statistics. Results: Data from 148 PwHA treated with emicizumab in 2018 were included in this analysis. Concurrent treatments included recombinant activated factor VII (rFVIIa; NovoSeven®; n=23 PwHA), factor VIII, (FVIII products other than Obizur®; n=9 PwHA) and aPCC (n=1 PwHA). Two adverse events were reported in 2018 (Table 1). One event was an acute reaction (rash), reported 48 hours after dosing of a PwHA treated with emicizumab only. He recovered from the rash; the frequency was 0.7% (1/148; 95% confidence interval [CI] 0.02-3.71%). The second event was a TE-a myocardial infarction that occurred 10 hours after emicizumab dosing in a PwHA age >65 years receiving emicizumab and aPCC. The frequency of TE events was calculated as 0.7% (1/148; 95% CI 0.02-3.71%). No TMA or anaphylaxis events were reported. Conclusions: Among PwHA treated with emicizumab at centers participating in EUHASS during 2018, only two adverse events were reported and there were no cases of TMA or anaphylaxis. While a full assessment is reserved for the final analysis, these interim real-world data are not inconsistent with the adverse event profile of emicizumab observed in clinical trials. No new or emerging safety signals for emicizumab were identified. However, this analysis was limited by the low number of emicizumab treated PwHA-especially in those without FVIII inhibitors, and relatively short exposure time to emicizumab. Disclosures Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Selak Bienz:F. Hoffmann-La Roche Ltd: Current Employment. Gadiraju:I am 50% shareholder in my own private limited company (Ravi Gadiraju Pharma Ltd): Current equity holder in private company; F. Hoffmann-La Roche Ltd, Safety Scientist (Mar 19 to current): Current Employment; Britannia Pharmaceuticals, Senior PV officer (Feb 17 to Mar 19): Ended employment in the past 24 months. Chang:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Kuebler:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company.

Assessment of cancer control capacity and readiness: the role of the International Atomic Energy Agency

2017 ◽  
Vol 18 (10) ◽  
pp. e587-e594 ◽  
Author(s):  
May Abdel-Wahab ◽  
Beatrix Lahoupe ◽  
Alfredo Polo ◽  
Eduardo Zubizarreta ◽  
Raja R Adnan ◽  
...  
Keyword(s):  
International Atomic Energy Agency ◽  
Cancer Control ◽  
Atomic Energy ◽  
Energy Agency
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