A hitchhiker’s guide to data review in an ongoing (“live”) study – part 2: data review for interim analysis
Part 2 – data review for interim analysis
If you are thinking of a clinical trial, you might ask yourself why and how data review for interim analysis can be a topic for a whole article.
In a clinical trial, a priori planned interim analyses, their nature and reason for performance are defined in the protocol. Data for such an analysis are then usually source-verified by the field monitor and central data review concerns only such verified data. Upon a tightly coordinated query process, where usually field monitors are involved again and provide support for the sites, the data base can be locked for the respective data analysis. At the time of data base lock, the data are usually “locked” by the data managers (i.e. can only be changed by the sites in the eCRF upon a reasonable and verified request) and thus usually do not change after the interim analysis has been performed.
Challenges for data review and interim analyses in a non-interventional study (NIS)
However, the situation is much more complicated in the non-interventional setting. In a NIS, the following characteristics may present a challenge for data review and interim analyses:
So what does this mean? Certainly, you could have a 100% SDV in a NIS and perform the data cleaning for your interim analysis as you would for a clinical trial, i.e. lock the data and unlock upon request only. However, this is an unrealistic scenario in the vast majority of NIS – in a study with thousands of patients, it is likely that dealing with data unlock-requests would be more than a full-time job.
Therefore, different approaches for central data review seem more efficient in the NIS setting. Importantly, there is not “the one” strategy that always fits and different studies and constellations require an individualized approach. In addition, the continuous and batch-wise review approaches are most effective when they go hand in hand in a coordinated manner.
Continuous data review
For studies with many patients, it is usually advisable to perform a data review of basic and/or critical data on a regular basis.
Assessing and closing failed edit checks on a regular basis often provides a good basis for a continuous data review. This allows not only to reduce a bulking up of workload for sites and data reviewers, but is essential for determining sites’ acceptance of the eCRF and perhaps identifying ways to improve the eCRF.
For instance: Only if you perform a regular data review, you will be able to realize if a majority of sites has troubles with a given edit check or question. Consequently, you can react before people get frustrated with the study.
The continuous data review also has direct projections to pharmacovigilance issues (see Part 1 – Data review for pharmacovigilance purposes) and can lead to identification of unreported (“hidden”) adverse drug reactions or other events of interest.
Batch-wise data review
This approach is especially useful when data that require review are to be reviewed in a longitudinal manner (i.e. in order to review data obtained at visit 2 you need to also check data obtained at visit 1).
This is often the case when the interim analysis should include patients who have reached a given relevant study milestone (e.g. when a given number of patients has reached a specific study visit). The batch then contains those patients with a defined degree of completeness of their data sets, which can be analyzed in a meaningful way.
There are many circumstances, where patient data that has already been subject to review may need to be reviewed again – e.g., when the data were reviewed for a previous interim analysis up to a certain visit and need to be cleaned again prior final analysis. In such cases, it may be beneficial to program listings where only de novo entered or changed data are displayed.
However, keep in mind that the plausibility of certain data entries in the last visit may only be judged when also looking at the data from the first visit. Therefore, listings and data presentations that allow for both – a quick overview on new entries as well as the whole picture – may be the most useful approach.
Summary and recommendations
Part 3 of the article series “A hitchhiker’s guide to data review in an ongoing (“live”) study” will be out soon… Register below to get a notification via e-mail!