Data Monitoring Committees — Are They Right for your Trial?
Data monitoring committees (DMC) have seen growing use in clinical research and can play a critical role in monitoring for unanticipated problems as trials progress. For this reason, it’s important to know the situations DMCs are best suited for, how they should function and what to consider when deciding to assemble one.
Given their greater presence in trials in the past decade-plus, DMCs may seem like a new concept, but they’ve actually been around since the early 1960s, says Judy Bebchuk, senior director of biostatistics for WCG Statistics Collaborative. A simple question is frequently asked about these committees today: are they necessary for our trial?
In Bebchuk’s view, recommended during a WCG CenterWatch webinar held last month, all trials need monitoring in some fashion, but not all will need to convene a DMC. DMCs are more beneficial in certain settings than in others, she explained, and it’s important to think about these settings when deciding whether a DMC is the correct monitoring body for a trial.
Trials with a major morbidity or mortality endpoint, for example, will almost certainly want to use a DMC, as will trials that have high potential for adverse events. And for trials where concerns over conduct or misconduct may arise, it’s often a good idea to have a DMC in place to keep tabs on what is occurring.
Sometimes a DMC may be required. Collaborative trials between industry sponsors and government or academia, for instance, will frequently be required to have one, and if institutional review boards (IRB) have concerns about monitoring and patient safety, they may call for assembling a DMC, Bebchuk says.
Even in situations where it isn’t required to have one, DMCs are still worth thinking about. Consider the risks that participants will face during the trial when you’re mulling this over, she recommends; protecting patient safety is, as always, paramount.
“You want to consider what your endpoint is, and if there’s a highly favorable or unfavorable result, or a finding of futility, you want the DMC to be able to stop the trial and interim analysis,” she said. “You want to make sure that the trial participants are not at risk.”
At the same time, consider how long the trial is anticipated to take. Depending on the length of the treatment period, a DMC may not be the most practical choice.
“They do take time and they do take more coordination,” she said. “If you’re running a very short-term trial, there may not be the possibility to constitute a DMC and have time to do a DMC review all during the treatment period of the study.”
It’s also key to think about the preplanned analysis that will occur during the trial. More complex trial designs, such as those that have a futility or early efficacy analysis, for instance, will probably want to employ a DMC, she says.
Sponsors that have settled on using a DMC for a trial will need to carefully review the committee’s composition, outline its responsibilities and ensure it is assembled and ready to go prior to the commencement of patient enrollment.
There are no set number of members for a DMC. According to Bebchuk, the ideal composition is two to three clinicians with expertise in the clinical specialties being investigated and at least one biostatistician with a firm grasp of trial statistical methods and the sequential analysis of trial data, with one committee member designated as chairperson. There may also be a medical ethicist on board or outside experts brought in as needed. The key is to have flexibility so that the appropriate expertise, whatever that may be, is present.
It’s essential that DMC members — who are external to the sponsors and investigators — can balance taking their time considering questions that arise during the trial while not taking too long to answer them. It’s equally critical that any DMC embraces a collaborative spirit and can be productive as a group.
“The committee is only going to meet once every four to six months, so it’s not that they get a lot of face-to-face time with each other, but it’s really important that they’re able to have good discussions when they do meet,” she said. “It’s usually up to the chair to elicit those discussions and to engage the other members in making sure that the reports are reviewed appropriately and that they make the appropriate decisions.”
In addition, it’s critical that the members named to the committee are free of conflicts of interest regarding the trial at hand. Bebchuk notes that this can be especially daunting for spaces such as rare diseases, which have smaller pools of experts.
The DMC’s initial meeting — the organizational meeting — is crucial to sustained efficiency and success throughout the trial. It’s recommended that this meeting is held in-person — even as virtual communication has become commonplace — and before recruitment starts. Nailing this meeting is essential, and it’s highly advised to go through it carefully to ensure the DMC is fully ready before the trial starts, even if initiation looms (CenterWatch Weekly, June 28, 2021).
Sponsors have a number of avenues when it comes to getting support on assembling and managing DMCs. A number of clinical research service providers offer this as a service, such as WCG, which has a global network of medical, statistical and safety experts that can serve as committee members and statisticians who are experts at writing DMC charters.
Besides sponsors, sponsor-investigators and their sites may benefit from hiring a third party to handle DMCs — and may need to if the IRB mandates assembling a DMC and an investigator has a conflict of interest, Sandy Smith, WCG’s senior vice president of clinical solutions and strategic partnering, told CenterWatch Weekly. And with staffing shortages still rampant, outsourcing the DMC may be an even more practical path to take.