Cytel Blog

In a previous post, I discussed the importance of proper use of CDISC Controlled Terminology (CDISC CT) in SDTM. However, the CDISC-CT is not the only submission terminology you need to be familiar with when building SDTM datasets to be submitted to the FDA (and similarly to the PMDA). As per the FDA Data Standards Catalog, when submitting datasets to the agency, you need to follow not only the CDISC standards (SDTM, ADAM, define-xml and CDISC-CT) but also a number of other submission terminologies. For example, this is the case of MedDRA when your SDTM package contains Adverse Events data, or WHO Drug Dictionary for Medications, but there are also a number of other submission terminologies you need to apply, particularly in the TS – Trial Summary Dataset.

A number of presentations and papers have been published discussing TS domain^[1] and clarify requirements that are not always fully clear in the SDTM IG or in the agencies Technical Conformance Guide.

In this blog, I focus on TS and discuss some specific parameters that you need to submit in TS using various “external” dictionaries, and help you understand how to find the correct term (and code).

The Christmas break presented an opportunity to make my first concrete steps into the CDISC Library. Overall, it was a pleasant “promenade”.

The CDISC Library forms the foundation of an ongoing transformation in the way we will access and make use of the CDISC standards to facilitate the long awaited and desired, end-to-end data process implementation (see also the CDISC 360 project).

With the availability of the CIDSC Library, vendors can now develop software which you can use to instantly access standards i.e., Standards Controlled Terminology or data standards (for example SDTM). Standards are now available in machine readable and non-proprietary format.

Can I submit software programs other than SAS? What software programs should I submit? Are sponsors required to submit executable programs?

Do I need to rename my software programs so that they all have the same extension e.g. “.txt”?

Can I make use of macros in my software programs and if so, should macros be part of the submission package?

What kind of documentations for software programs should I include in the submission package?

Do I need to follow any particular style and conventions when writing software programs that will be part of a submission package?

A single topic generates so many questions! Get the answers in this blog.

The Virtual PHUSE-EU CONNECT Conference was held from November 8 to 13 and the event was a great success, despite all of us missing the face-to-face contact.

The conference kicked-off on Sunday night with a Social Virtual event with a “Numerologist Show”. Of course this could not replace and compete with the usual “toast” we were used to do live, so we did it virtually (check out my LinkedIn post where I offer some cocktails recommendations and share the recipe of my favorite cocktail “The Negroni” with a bit of history. But please don’t do it before Friday night, you will need the weekend to recover).

Like every year, Cytel significantly contributed to the event as one of the official sponsors, running a workshop (“Predictive Analytics Using R”), chairing and co-chairing two streams (Machine Learning & Connected Health and Scripts and Macros), preparing four on demand presentations (in Application and Development, Coding and Tricks and Data Standards and Governance streams) and two posters.

In this blog, I focus on presentations related to data standards and data submission to agency, in general.

About three years ago, Cytel was helping a sponsor on a project where I had to conduct surveillance of some CRO deliverables, mainly for SDTM and ADaM packages. At first, I was involved in the review cycle of SDTM, and began by reviewing some initial mapping specifications including a draft SDTM Annotated CRF. The CRO in charge was quite experienced and there was nothing major to spot in all the different versions I had to review.

Surprisingly, it was not the case some months later, when I had to provide the same review support for the Biostatistics deliverables, specific to the ADaM package. The ADaM datasets overall were well designed, and there were no major open non-conformance issues. However, it was clear from the very beginning that there was something missing - a missing link between SDTM and ADaM.

“A good start is half the battle” (the Before) when submitting data to the FDA and there are a couple of cherries to put on top (the After) when your regulatory group has finally submitted the eCTD to the FDA^[1] . A good start is to have early discussions with the agency by regularly meeting them and sharing the status of your clinical data standards. While, the cherry on the top is the continuous support you need to guarantee to your submission project to promptly react when the reviewers come back with questions and additional requests during the review process.

CDISC standards have been around for a while with the first SDTM Standard version released in 2004. However, it was only in the last decade that it became “The Standard”, particularly when Health Authorities (HA), such as the US FDA and Japanese PMDA, made it a requirement for data submissions to support most of the regulatory requests for market approval. Additionally, most of the Pharma companies made the CDISC standards a part of their operational data model and consequently, the number of studies using the CDISC standards increased across phases of development.

The benefit of receiving data in standard formats was soon recognized by HA reviewers as they now require lesser time to understand the structure of the data they receive. Integration of data provided by different sponsors, for example on the same indication, for better understanding of safety signals, has become possible with data submitted in standard CDISC format.

However, the HAs such as the US FDA, soon realized that this was not enough, for two main reasons:

1. sponsors sometimes make bad or different interpretations of the standard
2. lack of standards or use cases in specific disease areas or indication

The first issue has been addressed by a number of specific HA conformance technical guidance ^[1,2] and regular public webinars where the HAs presented to the Industry real examples of bad standards implementations ^[3]. For the second issue, it was soon clear that the gap to be fixed was bigger and required more investment and resources. The CDISC Therapeutic Area User Guidance (TAUGs) are an “attempt” to fill this gap and reduce interpretation, and misinterpretation, of the standards ^[4].

From the time the COVID-19 outbreak was declared a pandemic, the number of studies conducted around the world to either diagnose, prevent or treat the virus literally exploded (1570 as on today, according to the Cytel Global Coronavirus COVID-19 Clinical Trial Tracker¹).

Moreover, the pandemic impacted the regular schedule of ongoing clinical trials. Health authorities such as the FDA, promptly provided recommendations in the form of questions and answers on how to handle “disruptions” due to the pandemic². These disruptions include a range of challenges including skipped assessments or study withdrawal.

“CDISC launched a task force in an effort to support CDISC members and the research community as they work tirelessly to discover critical breakthroughs to treat COVID-19 …. The task force was launched with the goal of developing Interim User Guide and Related material” said David Bobbitt, CDISC CEO, in an interview with Outsourcing-Pharma.com³. On April 21, 2020, the task force released two guidances. In this blog, I provide you with a quick summary of what these guidances address.

The two guidances are:

• Guidance for Ongoing Studies Disrupted by COVID-19
• CDISC Interim User Guide for COVID-19

Continue reading to learn more.

In the first part of this two-parts blog, I speak about how the European CDISC Committee (E3C) together with CDISC converted our physical event into a virtual one and was held on April 1-2, 2020. I provided a summary of the updates received from the three main health authorities - the US FDA, the Japanese PMDA and the European EMA.

This post offers an overview of the other sessions I attended at the 2020 Virtual CDISC EU Interchange. The agenda was well planned and organized. The distinguished speakers were extremely prepared and answered numerous questions after their presentations. Continue reading for further highlights from the event.