There are some very clear messages coming from FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). As of a meeting with CDER and CBER Representatives and the CDISC Executive Committee on 1 February, here are a few highlights:
- Use CDISC Standards (SDTM and ADaM) NOW in eSubmissions to CDER.*
- If you want high quality eSubmissions (which will be reviewed better and more quickly), start with CDISC CDASH for your case report forms when you plan your study.
- The expected transport format for the foreseeable future is SASXPT with Define.xml.
*NOTE: CBER plans to accept eSubmissions with CDISC standards sometime in 2010 but please contact Amy Malla about this in advance.
The CDISC business case (the full version is in the Members' Only Area), which was completed several years ago, indicates that there is significant time and money saved if CDASH standards are used for study data collection (CRFs). When CDASH is not employed, many have found that it does not work well to map (‘shoehorn’) data collected in other ways into SDTM at the end AND it is costly and time-consuming. Yet, despite this knowledge, I keep hearing about all of the legacy data conversion going on; while contractors doing the conversions make money, sponsors complain that implementing the CDISC standards is expensive….Sure it is, if you do mapping at the ‘back-end’. Instilling quality at the ‘front-end’ of a process has proven effective in several other industries (e.g. ‘lean production’). In this economic climate, I keep thinking we will see more ‘lean clinical research’, not only to yield higher quality eSubmissons but also since some have told us that they can start a study in 70-90% less time if they use the CDASH standards!
Okay, back to the topic at hand…. For the past several months, since CDISC did a Stakeholder Analysis late last summer on SHARE, we have been in ongoing discussions with representatives from CDER and CBER. They have been seeking input about why they are not seeing more eSubmissions using CDISC standards. One reason is that some were waiting for the HL7 messages. Well, the CDER and CBER Representatives said to us, we need to walk before we run. We need to have standard data NOW so that we can see what the issues are in using the CDISC standards (regardless of the transport format) and we can then provide helpful feedback to those who are preparing eSubmissions. And, we should not surprise the industry, we should be predictable in what we do; hence, we will not be switching to a new transport format in the foreseeable future….and certainly not until it is thoroughly tested and shown to be ‘net better’ than what we are doing today. (In fact, the PDUFA IT plan will be corrected; it is erroneous to communicate that in 2013 FDA will only accept HL7 transport formats.)
One thing that the FDA reviewers have seen in eSubmissions to date is that there is a need for augmenting the CDISC standards. The safety domains that are available apply across all studies; however, there is always ‘disease-specific’ data left over and users don’t know what to do with it. Many times it ends up in the Supplemental Qualifiers. Therefore, they want CDISC to speed up the rate at which we develop the standards around these therapeutic areas. More information will be coming on this topic in the near future (and it is very closely linked to the SHARE work). Another comment indicates that providing CRF data with submissions may be helpful (perhaps another opportunity for ODM?). In the interim, they recommend that anyone preparing for an eSubmission meet with their review division well in advance to work out how to handle these ‘extra’ essential data items.
In conclusion, we learned in our meeting with CDER and CBER Representatives that “use of the CDISC standards, refined and developed as needed, will result in high quality submissions that will be reviewed more quickly; as such, the likelihood of an approval on the first review cycle will increase”.
There is a Summary of the recent 1 February 10 CDISC Executive Committee-FDA CDER/CBER meeting in the Members’ Only Area of the CDISC website. Those of you who have not yet joined CDISC may wish to do so soon; there will be more interesting developments in the near future. This will no doubt prove to be an interesting year!