Ensuring trial validity by data quality assurance and diversification of monitoring methods

Abstract

Errors in the design, the conduct, the data collection process, and the analysis of a randomized trial have the potential to affect not only the safety of the patients in the trial, but also, through the introduction of bias, the safety of future patients. Trial monitoring, defined broadly to include methods of oversight which begin when the study is designed and continue until it is reported in a publication, has a role to play in eliminating such errors. On-site monitoring can be extremely inefficient for the identification of errors most likely to compromise patient safety or bias study results. However, a variety of other monitoring strategies offer alternatives to on-site monitoring. Each new trial should conduct a risk assessment to identify the optimal means of monitoring, taking into account the likely sources of error, their consequences for patients, the study's validity, and the available resources. Trial management committees should consider central statistical monitoring a key aspect of such monitoring. The systematic application of this approach would be likely to lead to tangible benefits, and resources that are currently wasted on inefficient on-site monitoring could be diverted to increasing trial sample sizes or conducting more trials. Clinical Trials 2008; 5: 49—55. http://ctj.sagepub.com

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References

Altman DG , Bland JM Absence of evidence is not evidence of absence. Br Med J 1995; 311: 485.

Sterne JAC , Davey Smith G. Sifting the evidence— what's wrong with significance tests? Br Med J 2001; 322: 226—31.

The DAMOCLES Study Group. A proposed charter for clinical trial data monitoring committees: helping them do their job well. Lancet 2005; 365: 711—22.

Grant AM , Sydes M. , McLeer S. , et al. Issues in data monitoring and interim analysis of trials (the DAMOCLES study). Health Technol Assess 2005 ; 9: 1—238.

Buyse M. , George SL , Evans S. , et al. for the ISCB Subcommittee on Fraud. Statist Med 1999; 18: 3435—51.

Ellenberg SS , Fleming TR , DeMets DL Data Monitoring Committees in Clinical Trials. A Practical Perspective John Wiley, London, 2002.

MRC/DH joint project to codify good practice in publicly-funded UK clinical trials with medicines. Workstream 4: Trial Management and Monitoring (http://www.ct-toolkit.ac.uk/_db/_documents/trial_MP.pdf (accessed 4th April 2007).

Al-Marzouki S. , Evans S. , Marshall T. , et al. Are these data real? Statistical methods for detection of data fabrication in clinical trials . Br Med J 2005; 331: 267—70.

The ESPS2 Group. European Stroke Prevention Study 2. Efficacy and safety data. J Neurol Sciences 1997 (Suppl); 151: S1—S77.

10.

International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. ICH harmonized tripartite guidelines. Guideline for good clinical practice E6. http://www.ich.org/LOB/media/MEDIA482.pdf (accessed 26th April 2007).