“I just want to know what we need to do?”, “why can’t they tell me what they want?”, “are standards mandated?”, “do we need to be CDISC compliant next year?” These are some of the questions I hear at clients and conferences. And the organisation being referred to is of course the FDA.
Well good news. They have indeed told us what they want. Well a significant part of the FDA has told us what they want. The Center for Drug Evaluation and Research (CDER) have released a succinct ten page text entitled, “CDER Common Data Standards Issues Document.” The document discusses the CDISC standards – SDTM, ADaM and SEND – their use, some CDER wishes when using the standards, terminology and highlights some common errors. You can find a PDF on the Study Data Standards for Submission to CDER web page (a very useful page, the PDF is the first in the list, but this is a direct link to the PDF).
The document is incredibly useful. Why? Well consider the opening sentence:
The Center for Drug Evaluation and Research (CDER) is strongly encouraging sponsors to submit data in standard form as a key part of its efforts to continue with advancement of review efficiency and quality.
Good, CDER wants standards. The remainder of the first paragraph then talks about the CDISC standards. So they want standards and they want the CDISC standards. The second paragraph reflects on the submissions CDER has received to date and comments that everything is not what it should be:
however, due to differences in sponsor implementation of the standard, CDER has observed significant variability in submissions containing “standardized” electronic clinical trial data. CDER has received numerous “SDTM-like” applications over the past several years in which sponsors have not followed the SDTM Implementation Guide.
The paragraph concludes with:
The goal of this document is to communicate general CDER preferences and experiences regarding the submission of standardized data in order to aid sponsors in the creation of standardized datasets.
So, they want standards, they want CDISC standards, they want them this way and please read the Implementation Guide. It seems pretty clear to me.
There are two final paragraphs on the opening introductory page, the first about the need to communicate with the center – please note the US spelling for all my US colleagues – regarding submissions. We all know nothing beats good communication and the final paragraph states that the document will be updated in the future and notes the CDER data standards website which is a very useful resource. The remainder of the document goes into details about using the standards and what CDER would like to see in particular circumstances. To get a flavour of the document see the contents in the image to the right.
I will draw your attention to three paragraphs at the bottom of page 3 and the top of page 4. The first of the three paragraphs starts with:
The ideal time to implement SDTM standards for representation of clinical trial tabulation data is prior to the conduct of the study. The use of case report forms that incorporate SDTM-standard data elements (such as with CDASH-style case report forms) allows for a simplified process for creation of SDTM domains. This approach is preferred to the alternative of collecting data in a non-standard format and then converting to SDTM format after the trial (legacy data conversion).
The document then discusses legacy data conversion and the need for traceability and concludes with words about the potential pitfalls of late-stage conversion:
CDER has received applications in which the converted SDTM data sets were not consistent with the submitted analysis datasets and study report analyses, thus causing confusion during application review.
This last point about consistency is important and I believe both this and the traceability problem will become important issues in the coming years.
There are a couple of additional references that are worth reading. One is the new draft amendment 1 to SDTM that can be found on the CDISC website while the second is a guide to ensuring that define.xml schema validates. The define document is not new as it has been around a good while but I think it’s existence is not well known.
In this post I have picked out particular quotes and presented them as though they are the most important items to note. They are not. The whole text is important and I recommend that those working in the area of submission and/or standards should read the whole document carefully.
So this is all related to CDER, what about the Center for Biologics Evaluation & Research (CBER)? Well look at the CBER web page because the center is accepting SDTM submissions but it would be best to follow the information on the web page.