Central data monitoring in the multicentre randomised SafeBoosC-III trial – a pragmatic approach
Authors: Olsen Markus Harboe , Hansen Mathias Lühr , Safi Sanam , Jakobsen Janus Christian , Greisen Gorm , Gluud Christian ,   The SafeBoosC-III Trial Group, Pellicer Adelina , Bargiel Agata , Hopper Andrew , Truttmann Anita , Klamer Anja , Heuchan Anne Marie , Memisoglu Asli , Krolak-Olejnik Barbara , Rzepecka Beata , Loureiro Bergona , Lecart Chantal , Hagmann Cornelia , Ergenekon Ebru , Hatzidaki Eleftheria , Mastretta Emmanuele , Dempsey Eugene , Papathoma Evangelina , Lou Fang , Dimitriou Gabriel , Pichler Gerhard , Vento Giovanni , Hahn Gitte Holst , Naulaers Gunnar , Cheng Guoqiang , Fuchs Hans , Ozkan Hilal , De Las Cuevas Isabel , Sadowska-Krawczenko Iwona , Tkaczyk Jakub , Sirc Jan , Zhang Jinhua , Mintzer Jonathan , De Buyst Julie , McCall Karen , Bober Klaudiusz , Sarafidis Kosmas , Bender Lars , Lopez Laura Serrano , Chalak Lina , Yang Ling , Cornette Luc , Arruza Luis , Baserga Mariana , Stocker Martin , Agosti Massimo , Cetinkaya Merih , Alsina Miguel , Fumagalli Monica , Suarez Olalla Lóepez , Otero Olalla , Baud Olivier , Zafra Pamela , Agergaard Peter , Maton Pierre , Viellevoye Renaud , del Rio Florentino Ruth , Lauterbach Ryszard , Borregas Salvador Piris , Nesargi Saudamini , Rite Segundo , Rao Shashidhar , Zeng Shujuan , Pisoni Silvia , Hyttel-Sørensen Simon , Fredly Siv , Oguz Suna , Karen Tanja , Szczapa Tomasz , Gao Xiaoyan , Xu Xin , Yin Zhaoqing 
Published: July 2021

Background

Data monitoring of clinical trials is a tool aimed at reducing the risks of random errors (e.g. clerical errors) and systematic errors, which include misinterpretation, misunderstandings, and fabrication. Traditional ‘good clinical practice data monitoring’ with on-site monitors increases trial costs and is time consuming for the local investigators. This paper aims to outline our approach of time-effective central data monitoring for the SafeBoosC-III multicentre randomised clinical trial and present the results from the first three central data monitoring meetings.

Methods

The present approach to central data monitoring was implemented for the SafeBoosC-III trial, a large, pragmatic, multicentre, randomised clinical trial evaluating the benefits and harms of treatment based on cerebral oxygenation monitoring in preterm infants during the first days of life versus monitoring and treatment as usual. We aimed to optimise completeness and quality and to minimise deviations, thereby limiting random and systematic errors. We designed an automated report which was blinded to group allocation, to ease the work of data monitoring. The central data monitoring group first reviewed the data using summary plots only, and thereafter included the results of the multivariate Mahalanobis distance of each centre from the common mean. The decisions of the group were manually added to the reports for dissemination, information, correcting errors, preventing furture errors and documentation.

Results

The first three central monitoring meetings identified 156 entries of interest, decided upon contacting the local investigators for 146 of these, which resulted in correction of 53 entries. Multiple systematic errors and protocol violations were identified, one of these included 103/818 randomised participants. Accordingly, the electronic participant record form (ePRF) was improved to reduce ambiguity.

Discussion

We present a methodology for central data monitoring to optimise quality control and quality development. The initial results included identification of random errors in data entries leading to correction of the ePRF, systematic protocol violations, and potential protocol adherence issues. Central data monitoring may optimise concurrent data completeness and may help timely detection of data deviations due to misunderstandings or fabricated data.