When new medicines and vaccines hit the market, their safety profiles are often incomplete, especially regarding their use during pregnancy. Still, pregnant persons often need to take medicines during their pregnancy, and this lack of safety information can lead to uncertainties and risks for both themselves and their developing child. As a result, pregnant people may avoid necessary treatment for fear of potential risks, or may unintentionally be exposed to medications that pose risks to them or their child. Without reliable data to make informed decisions, the risks of avoiding therapy cannot be weighed against the risks of undergoing treatment.
As pregnant persons are generally excluded from pre-marketing clinical trials citing ethical reasons, post-marketing surveillance is crucial to fill these knowledge gaps. VigiBase, the WHO global database of adverse event reports for medicines and vaccines, is one important source of such data. However, the absence of a pregnancy-exposure specific field in the ICH-E2B standard for transmitting reports between pharmacovigilance databases complicates matters. In other words, there is no designated indicator for pregnancy exposures on adverse event reports in VigiBase, making searching for such reports difficult.
This is where the new pregnancy algorithm developed by UMC comes into play. The algorithm, which is available in VigiLyze, aims to streamline and standardise the identification of pregnancy-related reports, making it easier for users of VigiBase to find relevant pregnancy cases.
The aim of the VigiBase pregnancy algorithm is to find case reports related to pregnancy exposures, with or without adverse events, affecting the pregnant individual or the unborn child. The algorithm does not aim to find exposures passed via breast-feeding or paternal exposures (e.g. exposure passed via semen or affecting the sperm).
Simply put, this algorithm follows a two-step process to identify pregnancy-related reports in VigiBase. First, it excludes reports where a pregnancy exposure is unlikely, such as those involving elderly individuals. This initial filtering helps to focus the search on a smaller set of more relevant cases. Next, the algorithm scans the remaining reports for specific information that can indicate a pregnancy exposure. It checks, among other things, if the route of administration is transplacental or if the adverse event or reason for using the medicine is pregnancy-related. This is a rule-based process, meaning it follows predefined rules to identify potential case reports.
How to use the pregnancy flag in VigiLyze
All users of VigiLyze and VigiBase Custom Searches can utilise the VigiBase pregnancy algorithm as a filter when performing searches.
In the qualitative view in VigiLyze, click on “Filter” -> “Patient” -> “Pregnancy” to apply the filter.
When using the algorithm, it is important to be aware of how it performs and what to expect from it. Of all the reports identified by the algorithm, how many are genuinely related to pregnancy? Additionally, how many of all actual pregnancy cases does it accurately capture? Our research team thoroughly investigated these questions. The answer to the first is that 92% of all reports flagged by the algorithm can be expected to be true pregnancy cases. This means that if you perform a search for pregnancy exposures and end up with 100 reports, around 92 of these will indeed be related to pregnancy. Regarding the second question, the answer depends on how pregnancy exposures were coded in the report. Since the data in VigiBase comes from all over the world, and spans back to 1968, it is very diverse. Pregnancy exposures are reported and coded in a variety of ways, depending on reporting format, time, and region. Looking at VigiBase as a whole, in this study the algorithm managed to capture 75% of all pregnancy cases. Narrowing this analysis down to only reports submitted in the current international transmission standard, ICH-E2B, the algorithm captures 91% of all pregnancy cases. Keep an eye out for more details on this evaluation in our upcoming research article, which is currently under review.
The VigiBase pregnancy algorithm offers a reliable and systematic way for identifying pregnancy-related reports within the database. We hope that this tool will enhance pharmacovigilance efforts concerning pregnancy exposures. Our next step at UMC involves applying the pregnancy algorithm in signal detection to explore how this can be done. Stay tuned: more research in this important area of pharmacovigilance is on the horizon.
Read more:
ICH-E2B: ich.org/page/e2br3-individual-case-safety-report-icsr-specification-and-related-files
ISPE Poster on the VigiBase pregnancy algorithm and evaluation: who-umc.org/media/j2cpykuc/pregnancy_poster_digital.pdf
