During this daunting and disruptive time, sponsors and CROs are actively seeking solutions and work-arounds to address the fact that monitors are no longer able to perform site visits to do SDV, review drug accountability logs, assess site compliance, and more.  Besides these important on-site tasks, monitors are also key players in ensuring that clinical data is accurate and complete.

Since it’s probably fair to say that Electronic Data Capture (EDC) systems are now almost universally adopted by sponsors for capturing data, there are still many features of EDC systems that may be under-utilized by study monitors/CRAs. In particular the concept of remote monitoring seems to be a perfect example. (Note that we are not discussing risk-based monitoring or centralized monitoring, per se, here.)

In typical EDC systems, there is quite a number of built-in functions which generate and create reports, raw datasets, and Excel-compatible files.  Each of these functions has advantages/disadvantages, and some tools may require more in-depth knowledge of the data structures in order to generate meaningful and accurate output.  These more “technical” tools are most used by Data Management/Statistics to review data and generate statistical output.   However, there are other options for extracting and viewing data that are very useful to study management and operations personnel.   In particular, monitors could use some of the following functions to download data and review the data for multiple purposes, such as:

• Check for logic and consistency of data: Using formulas and filtering tools in Excel, monitors can highlight potential issues in data entry, or catch safety signals.   This may seem unnecessary given that the EDC programmers have likely programmed edit checks to catch out-of-range data.  However, edit checks may not flag unusual increases/decreases in a particular safety or efficacy measurement over time.  And even if the EDC system has generated an automatic query to the site, it’s possible that a site has either not yet reacted/responded to the query, or they have responded by indicating the data is correct.  In either case, a monitor can issue a query to the site to prompt them to respond to the automatic query, or otherwise explain the concerning data value.
• Check for missing data: Identifying and managing missing data is going to be an important issue for all ongoing clinical trials in today’s pandemic environment.  Undoubtedly, subjects will either miss visits entirely, or may have partial assessments performed at a given visit. Most EDC systems have a built-in way for the site to flag data as intentionally missing, however the FDA Guidance on Conduct of Clinical Trials of Medical Products During COVID-19 Pandemic recommends that sponsors now implement the ability to capture a distinct status of data is missing due to COVID-19 related issues.   Monitors will have to train sites on how to deal with missing data in this regard.
• Query management: Most EDC systems offer built-in query metrics reports.  These might include topics such as:  number of outstanding queries; frequency of automatic queries fired; time to query resolution.  Monitors can view the information in these reports to determine if sites are not addressing queries in a timely manner.  Or, if a particular automatic query is firing more often than average, this might indicate the site doesn’t understand a data entry convention or the query itself is the problem (e.g., it was not programmed correctly).  Depending on the issue, a monitor for example could consequently set up an online training session with the site to review data entry guidelines/conventions.
• Check for timeliness of data entry:  By looking at visit dates, assessment dates and comparing those to the data entry date in the audit trail (if possible in your EDC tool), one can determine if sites are entering data into EDC within a reasonable timeframe (e.g. between 3-7 business days, depending on the Sponsor’s expectations).

These are just a few examples of the ways that monitors can review data off-line which will greatly contribute to overall data quality.  If a sponsor has adopted a risk-based monitoring (RBM) strategy, this will direct the monitor to focus on the high priority safety/efficacy data while reviewing the data. RBM would provide even more time for monitors to review remotely.Monitors may themselves need to be re-trained or reminded how to use these various tools within the EDC system.

This is the time to do the training, and this is the time to monitor as much as possible remotely. If you don’t see the reasons to do it now, when else? While many commentators seem eager to announce the demise of traditional trials and the supremacy of so-called “virtual” trials, it is possible and indeed necessary to continue to improve our use of existing powerful technologies in today’s trials.

For further discussion or information, contact Eve-Marie Whitsun-Jones, Principal Management Consultant, at ewhitsunjones@wcgclinical.com.