The Importance of a Single Document

While working within a Trial Master File (TMF), it can often seem like there is no end to the number of documents needed for a clinical research study. There are multiple documents for different aspects of a study – from trial management to site management, safety, statistics, data management and everything in between. But one document has always been our favorite and that is the noble Delegation of Authority (DOA) Log or Site Signature Sheet, as it is sometimes referred to.

Now the question you may be asking is, “Why? Why would you pick this specific document?” Glad you asked! We’ll explain a little bit more about this document from both a clinical research site and a TMF analyst’s point of view.

Let’s start with a short description of what the DOA Log is and the information it contains. Per ICH GCP E6(R2) section 8, the DOA Log/Site Signature Site exists “to document signatures and initials of all persons authorized to make entries and /or corrections on CRFs.”

However, is that all it really is?

Actually, it’s much, much more. The DOA Log, from a site’s standpoint, shows all staff members “authorized” to participate in study-related activities, as well as when that authorization began, ended, and/or changed. But why is this important especially when there are so many other things to worry about in a clinical study such as study visits, drug accountability, labs, regulatory issues, etc.? The short answer is…deviations. You begin to hear about (and maybe even fear) deviations from the first day you begin your career as it’s one of the biggest issues in clinical research.

What are deviations? Deviations are variations from the approved specifications in a protocol. Let’s review a few examples to better understand how big (or how small) a deviation may be and see how quickly deviations can add up during a research study.

Common examples of deviations include:

1. A study subject is unable to come into the site for their scheduled study visit, however they can make it in the following week.
2. The study staff is currently preoccupied with other study-related duties, so a subject’s Informed Consent Form is performed by a non-study authorized person.
3. A study coordinator is unable to come into the office for work so he/she gives their password to a co-worker so that person can enter the data from a subject’s visit that day.

Example 1 is very common in our experience. Is this under the staff’s control? Sometimes, but not always. When the Principal Investigator (PI) signs the Protocol Signature page, they are agreeing to conduct the study in the manner outlined in the protocol. The protocol was developed to attain specific objectives/endpoints and needs to be followed for those to be valid. When study-related examinations, tests, and/or other activities do not occur at the time points specified in the protocol’s schedule of events, the data produced may become skewed, and ultimately less helpful in determining if the objectives/endpoints have been achieved.

Example 2 would appear to be the sign of a very well-oiled clinical site. When one person is busy, another steps in to help so the day runs a little more smoothly for the subjects coming in for a visit.  However, this is a major deviation. Taking a closer look at this: Is the person assisting trained on the study? Can they answer all questions related to participation on the study? Without the proper training on the protocol, it’s unlikely and, therefore, they are not the appropriate person to review the consent.

Example 3 is something most people know is a big “no-no,” but in a pinch may falsely think it’s for the best. Believe us when we tell you it’s not! Not only is it an unauthorized use of systems, but it will cause deviations which will then again detract from the integrity and validity of the data.

That was a small look at what a DOA log is and how it can assist clinical research sites in preventing deviations. Now let’s take a look at DOA Logs from the standpoint of a TMF analyst.

We believe the DOA Log is one of the keystone documents in the file. What do we mean by keystone? It is a document that contains the information needed to cross reference other documents within the TMF and determine what should be filed for whom and when. It outlines which staff members were delegated to perform specific study-related tasks and when. Below is an example of a DOA log taken from the www.nih.gov website showing these specific tasks.

What information should a TMF analyst gather from this document? First, you can see who the PI is.  You can also see what date the PI was authorized to begin study-related tasks and if/when the PI ended his/her duties.

 

Based on this, the TMF analyst can determine that there should be a curriculum vitae (CV; signed and dated) on file for this PI. You can also determine the date that the CV should have been signed on (or before) based on the start date listed on the DOA Log. The PI should (in almost all cases) also have a copy of their Medical License (ML) on file. Similar to the CV, the ML should be filed in the TMF with the first copy being valid on the start date indicated for him/her on the DOA log. The ML also needs to be maintained in the TMF with renewals being filed before its predecessor’s expiration (with no gaps in coverage).

What else can we determine? Let’s take a look at the delegations. Each staff member is delegated duties by the PI which are spelled out on the DOA Log. Some of these delegated duties may require specialized trainings/certifications, which should be filed in the TMF. These training certifications should be completed before an individual’s start date listed on the DOA Log and maintained throughout their study participation. We know that the PI will be required to go into an electronic data capture (EDC) system at some point to review and sign-off on data entered. To do this, he/she would be required to have EDC training in order to access the EDC. This training should also be filed in the TMF.

These cross checks really highlight the power of the DOA Log. The review of one single document, the DOA Log, can provide a wealth of information regarding a site’s staff and the expected qualification documentation. By reviewing the DOA Log, one delegated staff member at a time, and confirming that each staff member has the appropriate documentation filed (CVs, ML, trainings, certifications, etc.), you can ensure that your TMF is complete and inspection ready.