Tudur Smith, Catrin, Stocken, Deborah D., Dunn, Janet A., Cox, Trevor F., Ghaneh, Paula, Cunningham, David and Neoptolemos, John P. (2012) The value of source data verification in a cancer clinical trial. PLoS ONE , Vol.7 (No.12). e51623. doi:10.1371/journal.pone.0051623 ISSN 1932-6203.

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Abstract

Background

Source data verification (SDV) is a resource intensive method of quality assurance frequently used in clinical trials. There is no empirical evidence to suggest that SDV would impact on comparative treatment effect results from a clinical trial.

Methods

Data discrepancies and comparative treatment effects obtained following 100% SDV were compared to those based on data without SDV. Overall survival (OS) and Progression-free survival (PFS) were compared using Kaplan-Meier curves, log-rank tests and Cox models. Tumour response classifications and comparative treatment Odds Ratios (ORs) for the outcome objective response rate, and number of Serious Adverse Events (SAEs) were compared. OS estimates based on SDV data were compared against estimates obtained from centrally monitored data.

Findings

Data discrepancies were identified between different monitoring procedures for the majority of variables examined, with some variation in discrepancy rates. There were no systematic patterns to discrepancies and their impact was negligible on OS, the primary outcome of the trial (HR (95% CI): 1.18(0.99 to 1.41), p = 0.064 with 100% SDV; 1.18(0.99 to 1.42), p = 0.068 without SDV; 1.18(0.99 to 1.40), p = 0.073 with central monitoring). Results were similar for PFS. More extreme discrepancies were found for the subjective outcome overall objective response (OR (95% CI): 1.67(1.04 to 2.68), p = 0.03 with 100% SDV; 2.45(1.49 to 4.04), p = 0.0003 without any SDV) which was mostly due to differing CT scans.

Interpretation

Quality assurance methods used in clinical trials should be informed by empirical evidence. In this empirical comparison, SDV was expensive and identified random errors that made little impact on results and clinical conclusions of the trial. Central monitoring using an external data source was a more efficient approach for the primary outcome of OS. For the subjective outcome objective response, an independent blinded review committee and tracking system to monitor missing scan data could be more efficient than SDV.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Health Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Clinical trials -- Methodology, Clinical trials -- Data processing, Clinical trials -- Quality control, Cancer -- Research
Journal or Publication Title:	PLoS ONE
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	2012
Dates:	Date Event 2012 Published
Volume:	Vol.7
Number:	No.12
Page Range:	e51623
DOI:	10.1371/journal.pone.0051623
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	23 December 2015
Date of first compliant Open Access:	23 December 2015
Funder:	Medical Research Council (Great Britain) (MRC), Cancer Research UK (CRUK)
Grant number:	G0800792 (MRC)

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