Data and Safety Monitoring in Clinical Trials

A Data and Safety Monitoring Committee (DSMC) is an independent body of clinicians, statisticians, epidemiologists and ethicists whose task is to review the status and conduct of a clinical trial and make recommendations to the clinical research group concerning the trial’s continuation, modification and/or publication.

While not all trials require a Data and Safety Monitoring Committee (DSMC), trials that address major health outcomes and are designed to definitely address efficacy and safety issues should incorporate a formal data and safety monitoring process. These pages are designed to assist clinicians to decide when and if a study requires a DSMC and how the MRSC can assist with the DSM of a trial.

Purpose of a Data and Safety Monitoring Committee:

A Data and Safety Monitoring Committee (DSMC) is an independent body of clinicians, statisticians, epidemiologists and ethicists whose task is to review the status and conduct of a clinical trial and make recommendations to the clinical research group concerning the trial’s continuation, modification and/or publication.

Main objectives of a DSMC

One of the primary objectives of a DSMC is to ensure safety of the trial participants. However other responsibilities include ensuring integrity of the data, monitoring progress of the research and early identification of problems arising. Therefore, the most important purpose is to ensure that the trial remains appropriate and safe for the individuals who have been or are still to be enrolled (Ellenberg 2003).

References:

Armstrong P, Furberg C. Clinical Trial Data and Safety Monitoring Boards. The search for a Constitution. Circulation 1995;91:901-904.

Ellenberg SS. Independent data monitoring committees: rationale, operations and controversies. Stat Med 2001;20(17-18):2573-83.

Ellenberg S, Fleming T, DeMets D. Data Monitoring Committees in Clinical Trials. A Practical Perspective. Chichester. John Wiley & Sons Ltd. 2003.

Rouse DJ. Data monitoring and safety committees and their operations. Obstet Gynecol Surv 2003;58(5):329-36.

Wilhelmsen L. Role of the Data and Safety Monitoring Committee (DSMC). Stat Med 2002;21(19):2823-9.

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When is a DSMC needed?

It is generally agreed that some kind of safety committee is required when any one of the following conditions is met:

  • When a clinical trial is large enough to detect important effects on mortality and irreversible morbidity rates.
  • When the risk of a treatment (whether experimental or control) is unknown monitoring is necessary because adverse outcomes may occur unpredictably, sometimes with grave results.
  • If the treatment to be tested is novel, ie little information on clinical safety?
  • When a therapy has a known risk of severe side effects.
  • Trials involving vulnerable populations such as children, pregnant women or the elderly?

The U.S. Food and Drug Administration has suggested that “DMCs should be established for controlled trials with mortality or major morbidity as a primary or secondary endpoint” and they “may also be helpful in settings where trial participants may be at elevated risk of such outcomes even if the study intervention addresses lesser outcomes such as relief of symptoms”.

References:
Cairns JA, Hallstrom A, Held P. Should all trials have a data safety and monitoring committee? Am Heart J 2001;141(1):156-63.

European Organisation for Research and Treatment of Cancer. Independent Data Monitoring Committees and Interim Analyses Policy.(POL004). Feb 2004 www.eortc.be

Pirotta M and Chondros P. Data monitoring (and safety) committees – what are they and why do we need them? Australian Family Physician Vol. 33, No 11, November 2004.

Rouse DJ. Data monitoring and safety committees and their operations. Obstet Gynecol Surv 2003;58(5):329-36.

U.S. Food and Drug Administration. Guidance for clinical trial sponsors. On the establishment and operation of clinical trial data monitoring committees. Draft, November15,2001.Available at:http://www.fda.gov/ cber/gdlns/clindatmon.htm. Accessed 16 June, 2005

Wilhelmsen L. Role of the Data and Safety Monitoring Committee (DSMC). Stat Med 2002;21(19):2823-9.

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Composition of a DSMC

Essential members:

  • Chair who has previous experience with a DSMC on administration and scientific issues.
  • Clinician with a knowledge and expertise of clinical trials, the scientific basis of the treatment being tested, and clinical management of the disease.
  • Statistician knowledgeable about statistical methods for clinical trials and sequential analysis of trial data.
  • Secretariat who has previous experience with the process of DSMC (this person may have non voting status).

Additional non essential members:

  • Ethicist knowledgeable about the design, conduct, and interpretation of clinical trials.
  • Consumer representative.
  • Other individuals as required may be coopted onto the committee eg epidemiologist, laboratory scientist, pharmacist etc.

References:

Ellenberg S, Fleming T, DeMets D. Data Monitoring Committees in Clinical Trials. A Practical Perspective. Chichester. John Wiley & Sons Ltd. 2003.

Rouse DJ. Data monitoring and safety committees and their operations. Obstet Gynecol Surv 2003;58(5):329-36.

Wilhelmsen L. Role of the Data and Safety Monitoring Committee (DSMC). Stat Med 2002;21(19):2823-9.

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MRSC Role in DSM

The MRSC can provide support to investigators for their data and safety monitoring needs for clinical trials. This can be in the form of a complete DSMC in collaboration with the chief investigator of a study or individual members of the MRSC can be utilised by staff to participate on a DSMC set up by the chief investigator of a study. Please contact the MRSC for further information on this service.

Additional Readings

Freidlin B, Korn EL, George SL. Data monitoring committees and interim monitoring guidelines. Control Clin Trials 1999;20(5):395-407.

Kerr D, McBride R, Shemanski L. Tips on using DMCs to improve trial efficiency and safety. Applied Clinical Trials 2004 March

Packer M, Wittes J, Stump D. Terms of reference for Data and Safety Monitoring Committees. Am Heart J 2001;141(4):542-7.

Pocock S, Furberg CD. Procedures of data and safety monitoring committees. Am Heart J 2001;141(2):289-94.

Sydes M, Spiegelhalter D, Altman D, Babiker A, Parmar M and the DAMOCLES Group. S ystematic qualitative review of the literature on data monitoring committees for randomized controlled trials. Clinical Trials 2004; 1:60-79

Enquiries

Please send emails to Amber.Baillie@mater.org.au.

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