Skip to main content

Research Repository

Advanced Search

Central adjudication of serious events did not affect trial's safety results: data from the Efficacy of Nitric Acid in Stroke (ENOS trial)

Godolphin, Peter; Montgomery, Alan; Woodhouse, Lisa; Bereczki, Daniel; Berge, Eivind; Collins, Ronan; Diez-Tejedor, Exuperio; Gommans, John; Lees, Kennedy; Ozturk, Serefnur; Phillips, Stephen; Pocock, Stuart; Prasad, Kameshwar; Szatmari, Szabolca; Wang, Yongjun; Bath, Philip; Sprigg, Nikola; ENOS Investigators

Central adjudication of serious events did not affect trial's safety results: data from the Efficacy of Nitric Acid in Stroke (ENOS trial) Thumbnail


Authors

Peter Godolphin

ALAN MONTGOMERY ALAN.MONTGOMERY@NOTTINGHAM.AC.UK
Director Nottingham Clinical Trials Unit

Daniel Bereczki

Eivind Berge

Ronan Collins

Exuperio Diez-Tejedor

John Gommans

Kennedy Lees

Serefnur Ozturk

Stephen Phillips

Stuart Pocock

Kameshwar Prasad

Szabolca Szatmari

Yongjun Wang

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine

NIKOLA SPRIGG nikola.sprigg@nottingham.ac.uk
Professor of Stroke Medicine

ENOS Investigators



Abstract

Background and Purpose: Central adjudication of serious adverse events (SAEs) can be undertaken in clinical trials, especially for open-label studies where outcome assessment may be at risk of bias. This study explored the effect of central adjudication of SAEs on the safety results of the Efficacy of Nitric Oxide in Stroke (ENOS) Trial.

Methods: ENOS assigned patients with acute stroke at random to receive either transdermal glyceryl trinitrate (GTN) or no GTN and to Stop or Continue previous antihypertensive treatment. SAEs were reported by local investigators who were not blinded to treatment allocation. Central adjudicators blinded to treatment allocation, reviewed the investigators reports and used evidence available to confirm or re-categorise the classification of event, likely causality, diagnosis and expectedness of event.

Results: Of 4011 patients enrolled in ENOS, 1473 SAEs were reported by local investigators; this was reduced to 1444 after the review by adjudicators, with 29 re-classified as not an SAE. There was fair agreement between investigators and adjudicators regarding likely causality, with 808 agreements and 644 disagreements (56% crude agreement, weighted kappa, κ = 0.31). Agreement increased upon dichotomisation of the causality categories, with 1432 agreements and 20 disagreements (99% crude agreement, kappa = 0.54). Repeating the main trial safety analysis with investigator reported events showed that adjudication had no effect on the main trial safety conclusions.

Conclusions: In a large trial, with many SAEs reported, central adjudication of these events did not affect trial conclusions. This suggests that adjudication of SAEs in a clinical trial where the intervention already has a well-established safety profile may not be necessary. Potential efficiency savings (financial, logistical) can be made through not adjudicating SAEs.

Journal Article Type Article
Acceptance Date Nov 14, 2018
Online Publication Date Nov 26, 2018
Publication Date Nov 26, 2018
Deposit Date Nov 15, 2018
Publicly Available Date Nov 15, 2018
Journal PLos One
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 13
Issue 11
Article Number e0208142
DOI https://doi.org/10.1371/journal.pone.0208142
Public URL https://nottingham-repository.worktribe.com/output/1268010
Publisher URL https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0208142