According to DAMOCLES study group (2005, p. 712), the main aim of different kinds of trial data monitoring committees is: to protect clinical trial participants, to perform constant oversight of their well-being and interests, to perform ongoing overview and re-assessment of new clinical trial data and outcomes, to assess safety and efficacy of investigational drugs, to advise an executive board of a trial whether a trial should be continued or early stopped on the basis of trial progress and risks observations.
The more complex a RCT is the more vigorous and extensive monitoring and oversight is required. Usually the need for involvement of oversight committees is determined by the risk profile of a certain trial, i.e. the more IPs, treatment schemes/arms, interventions are planned by a trial protocol, the higher risks are foreseen for participants, and the more complex and unclear outcomes are the more oversight will be needed and done. At institutional level there are several committees that perform oversight (e.g., IRB, TMG, DMC/DSMB, TSC), as outlined in University of Liverpool/Laureate Online Education (2010a).
RCTs will be first reviewed and approved by an IRB. Then it will be constantly overviewed by DSMB that will provide its recommendations to Trial Steering Committee (executive board) whether or not a RCT should be continued or stopped (if risks are too high/ if a planned outcome has been achieved early), or some changes should be implemented (to reduce risks for participants). But in certain circumstances it is just impractical to involve data monitoring board in a RCT overview if, for example, foreseen risks are minimal, or there are approved drugs to be compared in a RCT, or expected outcomes can be assessed only upon recruitment stop University of Liverpool/Laureate Online Education (2010b). However, it is better to involve both advisory (data monitoring) and executive (IRB/TMG/TSC) committees to be able to correct study conduct and study assessment at any stage of a RCT.
Nowadays there are no single unified requirements to charts of data monitoring observational and executive committees, but three main approaches, as summarized by DAMOCLES study group (2005, pp. 712-713) exist that are used in different institutions (except for NIH, whose employees must adhere to the first model only, according to Nussenblatt, R.B., Gottesman, M.M., 2007, p.123):
- DSMB is comprised of independent members only with no conflict of interests related to a RCT,
- DSMB consists of independent members but several study team members participate only during open sessions of the board without a vote,
- DSMB consists of both independent members and those with potential conflicts of interests, whereas all members can vote.
It is necessary to have independent members in such committees who will be able to make unbiased decisions (free of financial, personal, or professional pressure), as this will be the best guarantee of objective review and results (better protection for participants). However, though it is possible that personal conflicts of interest may bias decision-making by members that participate in a RCT under review, such members possess thorough knowledge of study aspects that may be extremely helpful in review and assessment of a RCT progress and outcomes.
Besides, one should remember that participation in a data monitoring committee requires not only professional expertise, but also extended time for participation in sessions. It is important to consider this when such committee members work voluntarily. The cons of such work is that theyir decisions will be unbiased, but there may be little or no motivation to dedicate required time for each session, which leads to less vigorous protection of study subjects.
- Bekelman, J.E., Li, Y., Gross, C.P. (2003) ‘Scope and Impact of Financial Conflicts of Interest in Biomedical Research: A Systematic Review’, JAMA, 289(4), pp. 454-465 [Online]. Available from: http://jama.ama-assn.org.ezproxy.liv.ac.uk/cgi/reprint/289/4/454 (Accessed: 15 October 2010).
- DAMOCLES study group (2005) ‘A proposed charter for clinical trial data monitoring committees: helping them to do their job well’, The Lancet, 365, February, pp. 711-722 [Online]. Available from: http://dx.doi.org.ezproxy.liv.ac.uk/10.1016/S0140-6736(05)17965-3 (Accessed: 15 October 2010).
- Nussenblatt, R.B., Gottesman, M.M. (2007) ‘Rules to Prevent Conflict of Interest for Clinical Investigators Conducting Human Subjects Research’. In: Gallin, J.I. & Ognibene, F.P. (ed.). Principles and practice of clinical research. 2nd ed. Amsterdam: Elsevier, p. 123.
- University of Liverpool/Laureate Online Education (2010a) Lecturer Notes from MCR Module 4 GOODCP, VideoTranscript, Week 2 [Online]. Available from: University of Liverpool/Laureate Online Education VLE (Accessed: 16 October 2010).
- University of Liverpool/Laureate Online Education (2010b) MCR Module 4 GOODCP, VideoTranscript, Week 2 [Online]. Available from: University of Liverpool/Laureate Online Education VLE (Accessed: 16 October 2010).