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Electronic Submissions for Paper People – Lifecycle and Linking

September 16, 2015 | BJ Witkin, Senior Manager | Regulatory Operations

We’ve talked about what goes in an eCTD submission, what you (or your publisher) need to create one, and what kind of information your publisher will ask you for at the start of a new application. Now let’s talk about the two HUGE advantages electronic submissions have over their paper counterparts: Lifecycle and Linking.

What is Lifecycle?

Lifecycle, in this context, means marking a document for replacement or deletion. The easiest way to explain it is to look at what happens to a clinical protocol over the course of a study.

Let’s say you submit a draft protocol for FDA review and comment. We’ll call this the original protocol. The FDA responds with suggested changes to the study design; you make these changes to the protocol and submit this new version, which we’ll call version 1.

In the electronic submission environment, version 1 now replaces the original version, and we say version 0 has been superseded by version 1. This is an example of lifecycling a document. We also say that version 1 is the current version of the protocol.

But what will the FDA reviewer see now? That depends on what he or she wants to see: the current view, or the cumulative view. FDAoptions

As its name says, Current View shows only the current versions of all the documents in this application.

Cumulative View shows the entire lifecycle of the documents—ie, all the versions which have existed throughout the lifecycle of the application. This way the reviewer has the option of seeing everything that’s happened to the documents in your application.

Protocols are the most lifecycled documents, but some other examples are:

  • Annual Report components (eg, the Investigator’s Brochure)
  • Form 1572s (eg, as sub-investigators are added/removed)
  • Module 3 documents

There’s another, less common, lifecycle operation: Delete.

Let’s say that you submit a protocol but later decide that you aren’t going to do the study. In this case you’d delete the protocol. It won’t show in Current View but it would still be available in Cumulative View.

Let’s talk about Linking

I’m going to assume you already know what linking is—formatting a reference to something (a table, data source, listing, publication, and so on) so when someone clicks it they’re taken to the referenced item.

The most common problem we see when people switch from paper to electronic is they want to link everything…because now they can!

Here are some recommendations from a publisher’s perspective:

  1. Only link the first reference of an item per page.
    If you refer to Table 14.1.1 five times on a page, they don’t all have to be linked!
  2. Only link something when it provides real value.
    You’re submitting an investigator update for study WD40-001. You don’t need to link to the protocol—you’re not asking the FDA Reviewer to read the protocol, you’re just mentioning it.
  3. Don’t link to a sequence (because you can’t!)
    In the paper world it was common practice to tell your reviewer that a document had been submitted in a previous sequence. You can still do that in eCTD, but bear in mind that every link must go to a document. Thus, if you put a sequence number in blue and expect your publisher to link to it, your publisher is probably going to ask you which document in that sequence you want to link to.

    It’s usually simpler just to reference the document you want to link to. That way the reviewer will know where he’s going before he clicks the link and can decide whether he wants to bother.

  4. Be careful linking to module 3 documents.
    Some publishers recommend that IND module 3 documents not be linked at all because they are most likely to change over time. We don’t go that far, but we do advise keeping these links to a minimum and trying to think long-term. Are you linking to a document that’s likely to be superseded? If so, consider the need for including a link.
     
    It’s probably helpful to remember that the Reviewer will see all of module 3 laid out in a navigation pane on the left side of the Viewer. Thus it’s very easy for your Reviewer to simply click the referenced document to go there.

And remember, this is just one publisher’s perspective – if you are working with a publisher outside of IMPACT (sacrilege!) make sure to agree on issues like these in advance of document preparation.

Now let’s see what you’ve learned:

Pop Quiz Question 1: How many times should you link Study WD40-001 in the example below?

Pop Quiz Question 2: What document should your publisher link to for the references to sequence 0003 and sequence 0004?

submission

Answer 1: Maybe 1, but certainly not 3.

Answer 2: Maybe the cover letter for each sequence. But consider this: the protocol submitted in sequence 0003 has been superseded by the one in sequence 0004…so why even bother pointing the reviewer to it? Furthermore, if we keep a link to the current protocol (see the previous answer), why bother linking to sequence 0004 just so the reviewer can see the protocol again?

My answer: I would leave the first reference to WD40-001 blue and link it to the current version of the protocol, just in case the reviewer wants to refresh his/her mind about this study. I would remove the entire sentence explaining when the protocol was submitted; the reviewer can see the protocol by clicking the link so everything else is redundant. Finally, I would change the remaining reference to WD40-001 (in the table caption) to black.

Personally, I love it when my regulatory person talks to me about the cover letter as s/he’s writing it so I can have some input on links. This is especially true when I’m working with external people, since they’ll often give me a pdf version of the cover letter and that severely inhibits what I can fix.

And don’t forget, if you ever need publishing help, don’t hesitate to contact us. We can’t wait to hear from you!

Category: Regulatory Operations
Keywords: eCTD lifecycle, eCTD publishing, electronic submission

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