Is there anything more fun than a book that opens with a map? You know you're in for a particular kind of reading experience when you turn the first page and see a map that depicts a fictional world. 

In recent years, clinical study teams have also employed maps to document data flow and Trial Master File locations.  We talked about data flow maps in a series of recent posts; today we'll focus on TMF maps.

The concept of a TMF map comes from section 8.1 of ICH's Good Clinical Practice Guideline, Revision 2. The following statement was one of the few additions to R2:

"The sponsor...should maintain a record of the location(s) of...essential documents...."

Pretty simple, but most TMFs we audit do not include a record of locations of essential documents. Why not?

Most Trial Master Files consist of a primary repository - frequently a CRO's electronic Trial Master File - and one or more ancillary repositories. Ancillary repositories are other places where documents that "permit evaluation of the conduct of the trial and the quality of the data produced" are maintained.  For example,

• Contracts with vendors are sometimes maintained in a contracts database
• Safety reports are sometimes maintained in a permanent safety database and not refiled in the eTMF
• Certificates of analysis for IMP are sometimes maintained in CMC's Quality Management System
• The audit trail for protocol deviations is sometimes maintained in a Clinical Trial Management System
• Statistical code is sometimes maintained in a statistical computing environment
• Regulatory submissions and correspondence are sometimes maintained in a Regulatory Information Management System

CROs who manage the TMF and the study teams that manage the CROs tend to think of the primary TMF repository as the only TMF repository.  They realize that other documents are maintained elsewhere, but this just doesn't seem relevant because they're not responsible for those records. When we interview teams during TMF audits, they tell us that of course the regulatory documents are with Regulatory Affairs, of course the contracts are with Legal - it goes without saying. But three years down the road, when a team of newcomers is preparing for inspection, that institutional memory is lost.  Imagine your grandmother burying treasure in her backyard and then shuffling off her mortal coil without revealing the location.  Hence, the map.

Teams who have wrestled with the TMF Reference Model and its hundreds of rows of 8-point inscrutable font are reluctant to map their TMF, but a TMF map doesn't have to detail the structure of each repository; it just has to point to each repository.   The map could be as simple as this: 

"All documents for this study are filed in [CRO's] [name of eTMF] repository, except for the following:

• Contracts for vendors contracted by the sponsor are filed in the sponsor's [name of contracts repository]
• Safety reports are filed in the sponsor's [name of safety database]
• Regulatory submissions and correspondence are filed in the sponsor's [name of regulatory system]"

That's it! Write it up and file it in your main eTMF repository, section 01.01.01, so anyone who opens it from now until the end of the study knows where documents are supposed to be filed. 

Of course, if you want to be creative, you could still draw a map and iron the edges to look like parchment, to inspire a sense of wonder in the inspector who picks it up in the future.