We are pleased to announce that we have submitted a total of 5 abstracts to the PHUSE EU Connect in Birmingham. We greatly appreciate the effort of the team that worked on this. Hopefully, we can travel with a large delegation this year to Birmingham. All the abstracts are collected below. We are curious to hear your thoughts on the abstracts through LinkedIn.

Standardisation in a fast growing environment; MDR, EDC and other abbreviations

by Louella Schoemacher

With a fast growing portfolio, the importance and need for standardisation increases. In order to keep up with the growing number of compounds, indications and studies the argenx Data Standards team implemented a metadata repository in 2021. By having a single source of truth for our metadata we aim to spend less time and resources during study set-up phase.

Standardisation however is a dynamic process. New vendors, new guidances and new insights are all in place to improve our processes and data quality, but can be a challenge in standardisation. How many versions do we need and how to best govern different versions? When is something study-specific and when do we decide to standardise? Subsequently, how can we use the metadata repository to further expand standardisation across other processes? What is the impact on upstream and downstream processes?

With standardising our CRFs and Define-XML files we aim to have more standardised raw data. This should enable us to ease the process of creating SDTM datasets. What other actions could we undertake to reduce the time and effort to manage and clean data and to focus on analysing the data not only within, but also across trials, to focus on the bigger picture.

Last year we presented our implementation findings. Now we aim to give a short recap, but to also guide through our current activities, learnings and other projects we are focusing on to standardise more of our processes.

The journey of preparing an ISS 

by Lieke Gijsbers

The integrated summary of safety (ISS) is a critical component of a submission to the FDA regulatory authority. For the ISS, data from different studies are pooled and harmonised to conduct the integrated analyses. Integrated SDTM/ADaM Define-XML and integrated Reviewer’s Guides (icSDRG and iADRG) may accompany the ISS to provide additional context and information about the integrated SDTM and ADaM datasets.

Based on a use case, we’ll explain in this presentation the approach we took to create the pooled datasets. Moreover, we’ll share our experiences regarding the creation of an SDTM and ADaM Define-XML for integrated databases as well as the icSDRG and the iADRG.

Setup of ADAE and ADTTE for Exposure-Adjusted Incidence Rate Reporting

by Mitchikou Tseng

Adverse events (AEs) reporting in Integrated Summary of Safety (ISS) can be a bit tricky when aggregation of AEs under the same treatment is not deemed suitable by the regulatory agency. Since we need to report AEs of two or more studies individually, analyzing the exposure-adjusted incidence rate (EAIR) is deemed more appropriate as compared to the usual crude rate analysis since it considers the different drug exposure duration of the subjects. The adverse events analysis dataset (ADAE) can be used directly to report results in your table utilizing a macro, or a time to event analysis dataset (ADTTE) can be additionally created to facilitate easy reporting of the EAIR. This paper will talk about how to setup ADAE and ADTTE to support the EAIR analysis and why this approach is more efficient, in my opinion, as compared to deriving EAIR directly at table level.

Bookmarking your aCRF without the manual effort

by Ramon Jakobs

Part of getting your study FDA submission ready is the bookmarking of the aCRF. This can be a tedious and labour-intensive task and is prone to human errors, but it doesn’t have to be. We would like to present a solution that can automate part of the process or even fully automate the bookmarking.

According to the FDA guidelines there need to be bookmarks present by form and by visit. The bookmarks are displayed as a long list in the aCRF. This long list can also be visualized as a matrix where the intersect of form and visit depicts the bookmark. This matrix is the basis of our solution.

Only the aCRF and visit schedule are needed to create the matrix, but if your study and aCRF allow it, even this can be automatically filled out for you. Our solution will create an xml file that contains code for the bookmarks. This xml file can be imported in your aCRF and will create bookmarks according to the FDA guidelines. That is all, your aCRF is now ready for submission!

Ensuring that a Define-XML is submission ready

by Lyanne den Braven

Define-XML is a required component of your submission to FDA and other authorities. It contains a lot of information and a lot of ground needs to be covered to ensure that all relevant information is correctly and accurately presented in the Define-XML. Luckily some of that information can be checked and verified by off-the-shelf tools (such as Pinnacle21 and more recently CDISC CORE) but what checks do they do? And what about the information that is not checked by these tools? When developing a Define-XML it’s important to understand what checks are needed, and how the Define-XML will be validated.

As a CRO, we develop and validate many Define-XMLs in studies that we manage and report. Clients and sponsors also expect us to ensure that their Define-XMLs are submission ready for studies that we have not been involved in. While the requirements and validation rules are the same in either situation, the validation approach may be different. After all, having or not having prior knowledge of the creation of the datasets is a crucial differentiator.