eCTD Leaf Titles

Leaf titles are an important part of eCTD submissions, but they are rarely considered outside of Regulatory Operations. While authors tend to focus on what their file is called, reviewers look at leaf titles, not file names.  Putting meaningful information into leaf titles makes submissions easier to navigate, and makes reviewers' jobs easier.

What Are eCTD Leaf Titles?

As files are attached to the eCTD backbone, several pieces of associated metadata are stored in the index.xml file, including file names and leaf titles.  Here's an example:

<leaf ID="a4928335f5a5bc2e59361e91"

application-version="Acrobat 5 (1.4)"

checksum="0a805abd4cc668a49a1994a"

checksum-type="md5"

operation="new"

xlink:href="m2/24-nonclin-over/nonclinical-overview.pdf"

xlink:type="simple" xml:lang="en" xmlns:xlink="http://www.w3c.org/1999/xlink">

<title>Nonclinical Overview</title>

</leaf>

Let's examine the metadata in detail:

  • The first line tell us that this is a leaf, and gives its unique ID number.  This ID number is used to track lifecycle operations in later sequences.
  • The next lines of metadata tell us that this is a pdf document, and give its checksum and checksum type.  The checksum is used to verify that a file hasn't changed since it was published; any change to the file invalidates the checksum.
  • Then we get the operation type, which in this case is new.
  • The xlink information is a link to the file.  The first line provides the path from the index.xml to the file, including the file name.  The second line defines what type of link it is.
  • Finally, we get to the title attribute, in this case, Nonclinical Overview.
  • The last line ends the description of the leaf.

Recommendations For Leaf Titles

Regulatory agencies have been clear that they want concise, descriptive leaf titles to aid their reviewers.  Most publishing tools have reasonably good default values, but some leaf titles require input from the publisher to make them useful.  Remember that leaf titles, not file names, are displayed when reviewers navigate your submission using an eCTD viewer.

Here are a few rules of thumb:

  • Always keep leaf titles short.  Titles appear in eCTD viewers the way that bookmarks appear in Acrobat.  Try to limit titles to about 60 characters so that reviewers can get all the information in one view.
  • For leaves with an operation of new, you can often use the leaf titles that the publishing software provides.
  • For replace or append operations, it's helpful to indicate that the leaf points to new information.  For example, if we replaced the file above, we might provide the title Updated Nonclinical Overview.  If you can succinctly describe what's new that's even more helpful.  If this document was part of an IND submission, a relevant title might be Updated Nonclinical Overview With Chronic Tox Results.
  • Ask study report authors to provide a short title, like Phase 3 Study in Relapsed Patients, instead of A Randomized, Double-Blind, Placebo Controlled, etc.  It's often helpful to include the study number in the title: Phase 2 Dose Ranging Study 123456.
  • For granular study reports, it's helpful to establish a convention that you follow consistently in all studies.  An example might be the study number followed by a description of the file: 123456 List of Investigators or 123456 Protocol Amendment 2.
  • Datasets and CRFs also have leaf titles.  It's much easier to find a dataset titled 123456 Antibody Data rather than AB.xpt.  For case report forms a useful convention might include a combination of study number, site number, and patient number.

Conclusion

Adding useful leaf titles to your submissions doesn't take much effort, and it makes reviewers' jobs easier.  There is not much detail on leaf titles in agency guidance, but reviewers consistently ask for better leaf titles in their presentations to industry.  The suggestions above should get you started on the path to better leaf titles.  For more information, search for "leaf title" in the documents below:

FDA Reviewer's Perspective on Leaf Titles

EMEA Guidance with Leaf Title Information