Hi everyone. I'm Elizabeth Sugar, and today we'll talk about trial Monitoring. Just to give you a little overview of what we'll talk about, first we'll start with the goals and responsibilities, then we'll talk about interim analysis and why and when you would do them, then we'll talk a little bit about the difference between safety and efficacy, and then finally wrap up with a little more technical discussion of statistical monitoring. Just to give you a little bit of background on my perspective, I've been both sides of the table for trial monitoring. As a trialist and a bio-statistician, I've monitored my own trials and presented them to others to be checked and I've also been on the other side of the table as a monitor, checking trials mostly in the academic setting. Let's talk about the goals and responsibilities of trial monitoring. What everyone thinks of when they hear about monitoring is participant's safety and of course that's incredibly important. But there are a lot of other things we look at when we monitor trials. We look at the integrity of the study design. We look at how the study is progressing in terms of recruitment and data collection. We look at the quality of the data that is being collected. We really focus on the risk-benefit ratio. Finally, at the end of the trial, how are the results interpreted? Now there are many people responsible for the monitoring of trials. The first is in the US an institutional review board or IRB. In other countries, this may be referred to as an ethics committee. Of course, the individuals running the study need to monitor the progress and quality as well. Another important player is a data monitoring committee or DMC, which is an outside independent monitoring committee. Finally, the regulatory agencies. In the US, this would be the Food and Drug Administration, the FDA. In other countries there are similar regulatory agencies. I won't discuss the regulatory agencies in depth since the requirements for each are different for each country. The role of the IRB, or ethics committee is to establish and protect the rights and welfare of human research participants recruited to a study. They look at the study documents, things like the protocol, the consent, and any information that is facing the participant. These could be advertisements like fliers or commercials, ads you might hear over the radio, these could be public websites that the participant can look at to find out more about the study. They also look at the data collection forms or information sheets that are filled out and read by the participants. The real focus of these committees is patient safety and the issues of coercion because we want to make sure that the participants are in no way coerced and are kept safe. Now the individuals running the trial also play a big role. This can actually be many different people in and of itself. This can include the funding agency, the principal investigator, for larger trials there might be a group called a coordinating center, which talks to different sites in multi-site trials and collects all the data together. They review the site training, the study progress, recruitment, data collection, and quality, as well as adherence to study protocols and guidelines. Now their focus is not just patient safety, but operational issues in running a trial and data quality. The data monitoring committee is an independent body charged with oversight of a trial. Now the size and composition of a data monitoring committee may depend upon the type of trial or the risk of the trial. At the core, there are at least two physicians and a statistician or an epidemiologist. Other specialists may include ad hoc consultants or ethicist. Responsibilities include protecting patient safety, monitoring, recruitment, and compliance with study protocols, the evaluation of the risk benefit trade-off, and ensuring an appropriate interpretation of the results at the end of the study. Now, the board reviews the clinical performance, the influence of new data from outside the study, which may change the risk-benefit ratio or influence other factors in the trial, as well as proposed changes or additions to study materials such as protocol modifications, press releases, the inclusion of additional studies looking at other research questions which are called ancillary studies, safety data, and efficacy data.
