6 Critical Factors for Prevention & Mitigation
Collecting clinical data that are accurate, reliable and of high quality is the corner stone of every clinical trial. Data are collected throughout the entire lifetime of a study, and it’s not unusual that interim analyses and database locks occur at several timepoints in the study.
These periods are usually very busy for the clinical operations team with a lot of reconciliation, queries resolution, and source data verification activities. During data analysis CRAs work with the eCRF on a daily basis and are the main point of contact for Investigational Sites. Which is why, for the clinical trial Sponsor, CRAs are their best allies in ensuring each data cleaning period in the study runs smoothly.
Outlined below are six critical factors to consider when striving to efficiently prevent and mitigate data entry/verification issues and backlog.
Proactivity is Key
Proactivity is without a doubt your best approach for efficient data entry and data verification. This means keeping on top of data entries made (or not made) by site personnel and timely monitoring throughout the course of your study. This ensures data are reviewed regularly, queries are fired in an ongoing manner, and are quickly addressed. As CRAs implement weekly contacts with site personnel to discuss any study related issues, they also verify data are entered in a timely manner to avoid a backlog of data entry and/or query resolution. This periodic, consistent follow-up also provides regular opportunities for site personnel to ask any questions they have about the eCRF completion and queries, as well as progress on study enrollment.In the case of a database lock (DBL) where the Investigator signature is required, a sound proactive practice consists of inquiring ahead of time about the investigator’s availability around the date of the planned DBL and confirming if their data base access is still active. This allows sufficient time to prepare a back-up plan if needed to minimize the impact of last-minute surprises.
Make Use of Available Reports
Electronic data capture systems used in clinical studies commonly feature a wide range of report types, with several relevant reports for various roles. The effort invested by clinical operations team members to familiarize themselves with pertinent report functions is time well spent.
Understanding what reports are available and how these can help track the eCRF data status for a specific Site or subject increases overall study management effectiveness. Such reports can be filtered (ex: for a particular country or Site) and distributed to CRAs on a weekly or bi-weekly basis. This practice supports CRAs in proactively managing the contacting their assigned Sites to request that data be completed or corrected.
If such reports are not directly available in eDC, collaborate with the study data management team to obtain useful reports upon request. Work together to determine what data you would like to see and at which frequency you need visibility. Doing so allows for better oversight of data entry activities.
When possible, CRAs should take the initiative to share site specific reports with their Sites about pages pending completion, open queries, etc., so everyone has a clear understanding of the study status for and at each Site.
If the above actions are undertaken regularly, when the time for data analysis is at hand there is no back-log of data, and the focus is where it should be: on reconciliation, data verification, and queries resolution. This results in a more easily manageable and smooth data cleaning period for the DBL and Sponsors’ subsequent analysis for indicators.
Frequent Contact with Sites
At Scimega, we consistently work to build and maintain strong relationships with our study sites. This requires considerably more than calling site personnel with urgent requests.
We focus on providing support of value to our Sites, and this includes our CRAs’ commitment and availability to answer any questions, and help with any doubts that arise, issues or concerns site personnel may have about a study. Our weekly contact with site personnel ensures your study remains top-of-mind amidst a Site’s busy research schedule, and serves to provide reminders about what needs to be addressed next. It’s more efficient to resolve a few items a week than wait for the data cleaning period and become overwhelmed by a multitude of issues at that critical and time sensitive point in the study.
Also, it’s very important for data integrity to instruct Sites to seek guidance in case of any doubts that arise when performing study tasks, and provide them ample opportunity to air these. This pre-emptive approach means site personnel are provided the guidance needed, and are not left to make assumptions about how to enter data, only to realize later that’s not what the Sponsor expected or protocol required. This avoids many unnecessary queries that are time-consuming to address and verify. Reliable CRA availability helps maximize site resources and avoid extra work for everyone.
Old Queries? They Remain for a Reason!
It’s not unusual in a clinical trial to have one or several study sites with old outstanding queries. When this occurs, it should sound an alarm! If site personnel are regularly addressing most queries while some age and remains open for 90 days or more, there’s a reason, and you need to know what it is.
It could be because the query text is not clear and the site personnel need clarification, or perhaps they don’t exactly know how to address it, or answering the query will take a lot of work there just isn’t time for from the Site’s perspective. CRAs should be encouraged to look out for and investigate these outstanding aging queries, responding to Sites with clarification and guidance. In some cases, data management may need to become involved in order to re-phrase the query or provide explanations on exactly what’s expected. Resolving all queries (especially those older outstanding ones) in a timely manner prevents a backlog of complicated queries emerging for hasty resolution at the time of the database lock.
Set and Respect Transparent Deadlines
Time is a precious resource in the field of clinical research, and everyone involved in a study is busy. Site personnel are often dealing with several Sponsors’ study deadlines and it’s not always easy to prioritize tasks.Sponsors’ clarity and transparency with their CROs and Sites about expected deadlines and objectives for an interim analysis or database lock is extremely important. If site personnel know what is expected and the required completion date, they can more effectively organize their workload around your timelines. Understanding why meeting a particular deadline is important helps obtain collaboration from everyone working on the project. Site personnel want your study to succeed, and are not necessarily aware of the constraints and demands you and other study stakeholders face. Providing a little background on the other parties involved in your study, and on what the repercussions of not meeting a deadline can mean are certainly helpful in obtaining their full collaboration.
Good Communication Flow between Sponsor and CRO
A lot happens on a daily basis during data cleaning: significant quantities of data are entered, updated, reconciled, queries answered, etc. At the forefront of this activity, CRAs are the ones who know exactly what the site status is.
As the study Sponsor is often dealing with several countries, project managers, and time zones, at this crucial time Sponsors are dependent upon reports from their CROs about the status and progress at study Sites.
Scimega employs a resource model that provides their Study Sponsors with daily updates on progress for each Site involved in their study, including action plans for pending action items. This is a result of strong and proactive study oversight that effectively reassures everyone involved.
Interim analysis or database locks don’t have to be excessively busy and stressful!
The key really is to be proactive and stay on top of data entry throughout the course of the study in a timely and efficient manner.
As noted above, tools and techniques are available to make this process easier. Involve your Sites and your CRAs from the beginning, maintain good communication with the different parties involved in your study and you’ll find that data cleaning can actually be managed quite smoothly.
It’s never too late to do better. If your last data cleaning did not go well, make a list of the lessons learned and start implementing new habits right away! Let your most recent database lock be your fresh start to tackle future threats to your clinical trial caused by data entry issues and backlog!
Contributed by: Maëva Roques, M.Sc., Clinical Trial Leader