Central data monitoring in the multicentre randomised SafeBoosC-III trial – a pragmatic approach

Abstract

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.

One-step laparoscopic cholecystectomy with common bile duct exploration and stone extraction versus two-step endoscopic retrograde cholangiography with stone extraction plus laparoscopic cholecystectomy for patients with common bile duct stones: a randomised feasibility and pilot clinical trial—the preGallStep trial

“…The variations in the inclusion procedures of each trial site due to patients being both acute and ambulant could cause one of the bigger challenges in estimating feasibility issues and implementing changes in procedure in a larger pragmatic trial. We will implement a central data monitoring scheme designed to illustrate “inter-site” differences and the causes of these [ 30 ]. These differences are both regarding screening and randomisation, but also executing the trial interventions and follow-up.…”

“…Central data monitoring will be initiated after the inclusion of one third of the participants and carried out every third month by a central data monitoring group consisting of investigators, including experienced clinicians, statisticians and trialists. The aim of the central data monitoring is to optimise completeness and quality and minimise deviations through blinded evaluation of the data [ 30 ].…”

The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial

“…Monthly central checks will focus on recruitment to the trial, the quality, completeness, and timeliness of data entry in the electronic case report forms (eCRF). The central data monitoring will be conducted as described by Harboe Olsen et al [ 20 ].…”

Centre for Statistical and Methodological Excellence (CESAME): A Consortium Initiative for Improving Methodology in Randomised Clinical Trials

“…Central data monitoring Data monitoring of clinical trials is a tool aiming to reduce the risks of random errors (eg, clerical errors) and systematic errors, which include misinterpretation, misunderstandings, and fabrication. 34 Traditional 'good clinical practice data monitoring' with on-site monitors checking collected data against source data is often not sufficient to ensure optimal data quality. It also increases trial costs and is time-consuming for the local investigators.…”