Data monitoring

Item 28a: Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and funder; conflicts of interest and reference to where further details about its charter can be found, if not in the protocol. Alternatively, an explanation of why a DMC is not needed.

Example

​

“The DMC [Data Monitoring Committee] will be responsible for safeguarding the interests of the trial participants and for assessing the safety and efficacy of the interventions during the trial. Also, the DMC is responsible for monitoring the overall conduct of the trial. The DMC consists of three specialists with expertise in anaesthesiology, intensive care, and clinical research and thus holds clinical and statistical expertise as recommended [Reference]. The DMC is independent of the sponsor and other members of the research staff. The DMC will review de-identified data for safety at five predetermined milestones (200, 500, 1000, and 1500 enrolled patients), but can, at any time, require extra reviews. Unless group differences are observed that require unblinding (as determined by the DMC), the DMC will be blinded to treatment groups. The trial will continue while the DMC reviews data. After a review, the DMC will prepare a short report for the steering committee with recommendations for continuation, modifications, or termination of the trial. The final decision on potential modifications or termination will rest with the steering committee and the sponsor-investigator. A detailed charter for the DMC will be available on the STOP-COPD trial website after patient inclusion starts ” [449].

“The independent statistician of the IDMSC [Independent Data Monitoring and Safety Committee] will conduct one blinded interim analysis after 500 participants (50%) have been followed for 28 days. The alpha value for the interim analysis is 0.0054 as by the O'Brien-Fleming bounds, which preserves type I error at the usual 5%. [reference] The trial will be stopped early if the alpha cut-off is crossed at the interim analysis. The IDMSC will be provided with the following outcome data with the two groups masked (eg interventions coded as 0 and 1):

- Days alive without life support (ie invasive mechanical ventilation, circulatory support or renal replacement therapy (including days in between intermittent renal replacement therapy)) from randomisation to day 28.

- Number of participants with one or more SARs [serious adverse reaction] or SUSARs [suspected unexpected serious adverse reaction] from randomisation to day 28 ” [450].

​

Explanation

​

Some trials will plan a periodic inspection of the accumulating outcome data by trial group to be able to discontinue the trial if the accumulated data show clear benefit or harm. Data monitoring can also inform other aspects of the trial, such as recruitment, and identify the need to make adjustments. In many cases, trials with a Data Monitoring Committee will be those of long duration and with interventions with known risk of harms. However, many trials do not need a formal Data Monitoring Committee [451], typically trials with a short duration or known minimal risks.   

A Data Monitoring Committee will often consist of members from a variety of disciplines [364, 452, 453]. The primary role of a Data Monitoring Committee is to periodically review the accumulating data and recommend to the trial steering committee or sponsor whether the trial should continue, be modified, or be discontinued. Independence, in particular from the sponsor and trial investigators, is a key characteristic of the Data Monitoring Committee and can be broadly defined as the committee comprising members who are “completely uninvolved in the running of the trial and who cannot be unfairly influenced (either directly or indirectly) by people, or institutions, involved in the trial ” [364, 453]. 

The use of a Data Monitoring Committee was reported for 29% of trial protocols approved from 2000–2003 in Switzerland, Germany, and Canada [454, 455], and for about 40% of trials registered on ClinicalTrials.gov from 2007–2010. Reviews of two samples of 108 and 292 trial protocols from 2016 found that 58% reported whether or not there would be a Data Monitoring Committee [9, 10].

The protocol should state whether or not there will be a Data Monitoring Committee, with rationale. If a Data Monitoring Committee is planned, the protocol should name its chair and members. If the members are not yet known, the protocol can indicate the intended size and characteristics of the membership. The protocol should also indicate the Data Monitoring Committee’s roles and responsibilities, planned method of functioning, and degree of independence from those conducting, sponsoring, or funding the trial [54, 364, 453, 456]. A Data Monitoring Committee charter is recommended for detailing this information and should be included or referenced in the protocol [54, 453].

​

Summary of key elements to address

• Whether a Data Monitoring Committee is planned, with rationale

• If a Data Monitoring Committee is planned:

  • Composition of the committee

  • Size and characteristics of membership (e.g., type of expertise)

  • Chair and member names (if known)

  • Roles and responsibilities

  • Reporting structure

  • Method of operation (e.g., meeting format and frequency)

  • Degree of independence from those conducting, sponsoring, or funding the trial

  • Reference to Data Monitoring Committee charter where further details can be found