May 8, 2012 at 3:01 PM by cdisc
Novo Nordisk Presentation during the CDISC Interchange Europe 2012
Gitte Frausing of Novo Nordisk presented on her CDISC SEND experience during the CDISC European Interchange in Stockholm on 18-19 April. The focus of her presentation was on lessons learned from the FDA-SEND Phase 2 Pilot, in which Novo Nordisk participated. The value of a close collaboration among the SEND team, the CDISC Terminology team and the FDA was readily apparent from this presentation.
Gitte described how different terms with varied definitions may cause inconsistencies and inaccurate results within the non-clinical analysis. She illustrated her point of view with some examples of inconsistencies within the area of microscopic findings: one of the findings showed a liver having a 3 millimeter pale area with surrounding hemorrhage, which is actually considered two findings in SEND and should not be included in the same record. Gitte also mentioned that having no place to incorporate certain data in the SEND domains caused loss of information due to the lack of standardization in the data capture phase. This was one of the ‘lessons learned’ that the FDA agency has found during their analysis of the submitted data.
Another example Ms. Frausing provided was that FDA asked Novo Nordisk to test the terminology for the severity variable in SEND standard; the outcome was to ensure the validity of the terminology already created by the SEND terminology team. She also mentioned that FDA observed that Novo Nordisk was using log transformed data within their analysis process, while this log transformed data did not exist within their datasets. The FDA recommended that they create a test code for log transformed data and incorporate it into the submission datasets. Thus, the presenter cautioned that FDA would check or need the smallest details as they look at your data and it is important to align regulatory expectations with sponsors capabilities prior to submission. She advised on adopting the SEND standard as early as possible in the data capture phase, based on this experience when the FDA compared the final PDF file with the migrated data and found some inconsistencies.
Yet another example provided by the presenter was based upon the size of the study and practicality of execution. Having many animals in a non-clinical study makes it difficult to conduct the tests within the same day, hence they may be divided into two days (half of the animals on the first day and the second half on the next day). In order for the FDA to be able to analyze all the data together, the variable “VISITDY” (planned study day of assessment) must be populated the same. That is, with the first day of an assessment that may span multiple days. The ‘grace days’ should be described in the define file. Thus populating the “VISITDY” variable appropriately is critical for the FDA’s ability to analyze the datasets.
Creating these concepts was a new experience for Novo Nordisk. They used Excel templates for that purpose, and these templates worked fine for the pilot, but not as a permanent solution. Gitte stated that variables are more than they appear, especially the “VISITDY” variable mentioned previously. There were also issues with creating labels. She explained that, if one just looks at the domain, it will appear straight forward, but one may not populate them correctly without knowing the assumptions and if one has not read the CDISC SEND implementation guide (SEND IG), especially the first four chapters.
The presenter commended the collaboration between the highly skilled CDISC SEND team and the Novo Nordisk experts toward finding the solutions. Gitte Frausing clarified for the audience that the initial intent with SEND was not to impose any new requirements, but to only find a standard way to tabulate the data as it is captured today. However new requirements to our data in unavoidable, as we have to enforce CDISC Controlled Terminology in areas where they haven’t existed before and push that all the way up in the data chain and build the architecture processes all around this. She also clarified that the science will change for the better as standardized data will add more quality into our science. In addition, having scientific standardized data at the end of the study will enable everyone to leverage more scientific benefits from the data.
The draft guidance for standardized study data was published by FDA on 17 February 2012. In combination with PDUFA V section 12 (a very important section, which the presenter advised all to read), many of the CDISC standards, including SEND becomes submission requirements in the very near future. The draft guidance for standardized study data will be finalized no later than April 2013 (and possibly earlier) and will be legally enforceable by PDUFA V and the timeline within it.
Additional SEND projects:
The SEND team is working very closely towards a pilot for Safety Pharmacology, Cardiovascular and Respiratory domains. They also have Reproductive Toxicology domains and are starting to work with fertility studies; this will be piloted with FDA by the end of 2012, beginning of 2013. Some of the other projects the team is working on are the safety studies and the complex multi-generation reproductive toxicology study. They are also looking at the CNS safety pharmacology.
In addition, the FDA-PhUSE Computational Science Seminar working group is developing a roadmap for prioritized areas in the non-clinical arena. FDA is encouraging the industry to participate in that significant effort, so this is a very good opportunity to join and participate.
The presentation ended with questions from the audience, one of which was as follows: “Since you mentioned Novo Nordisk was not used to doing things in a way that fit the SEND model, does that mean that you will change your way of doing things?”
Ms. Frausing’s answer was quite clear: “We do not have a choice; we have to change our way of doing things.” On the other hand, she clarified that they will try to maintain the integrity of the whole analysis of their studies because each study is analyzed in a pretty standard way in the non-clinical world. The idea of collecting a fixed set of parameters and analyzing them in a fixed way will not change, but they have to introduce some new concepts.
The SEND team has been doing excellent work and collaborating in a very positive way with FDA. We commend their progress and thank Gitte Frausing for this educational presentation.
By Diana Harakeh
CDISC, Manager of Communications