Source notes and CRF

It was good to see the activity happening on this site while I was away.
Vishal’s query generated a lot of interesting threads of conversation with notable contributions from Rakesh, Rahul, Jayesh and Dilip.

I also had a lot of sms queries about the poll and its trends.
Dr Manjunath shared his concerns about the limited choices of imparting GCP training and understanding. He wonders whether apart from learning while working is there anything we can do apart from the workshops that offer GCP training.

Do write with ideas on this. And we will take this up in another blog.

For today, the focus is the source notes vs. CRF debate.
The poll reflected that it is possible and all right to directly record in the CRF, but there were a significant number of poll participants (30%) that felt that source notes are IT! (And by know you would have learnt you can’t ignore stats in Clinical Research!)

So where are we?
Whenever I have asked this question of people, I first get a little lost look, kinda wondering whether this is a trick question or what. It isn’t the same like the one my boss gave me 8 years back, coz by now I have managed to gain a little bit of credibility on my capabilities. Some relief!
But it is a look nevertheless!

The sample responses one gets usually go like this-
1.Sudden onset of selective deafness.
2.Ahem, huh! I guess it depends!
3.Of course one needs source notes for everything on the CRF, how else are we to do Source data verification and then what else will we do during the monitoring visits????

And so the debate goes on and so does the documentation.
If you were to take a spot survey of what is difficult about Clinical trials, the answers one would most likely get are documentation and the unending regulations.

Increasing and excessive documentation seems to have become the norm of CR life.
Document what you do and do what you document has become Do what you document and Document what you do, but remember to transcribe all!!

Lets examine what GCP and the regulations demand.

Section 6.4.9 of ICH GCP asks for -The identification of any data to be recorded directly on the CRFs (i.e., no prior or written or electronic data), and to be considered source data.

This section is part of 6.4 that details the trial design in the Clinical Trial Protocol.

In Chapter 8 which lists the Essential Documents for the conduct of clinical trials,the purpose of source documents is described as "to document the existence of the subject and substantiate integrity of trial data collected.To include original documents related to the trial,to medical treatment,and history of subject" and these source documents are to be located at the investigator site.

Further,the purpose of signed,dated and completed CRF s is described as" To document that the investigator authorized member of the staff confirms the observations recorded.The CRF itself is described as a document to record all of protocol-required information to be reported to the sponsor on each trial site.But protocol specific information does not necessarily create a complete audit trail.

You will agree with me that a good document follows ALCOA, i.e it is Attributable, Legible, Contemporary, Original, and Accurate and the whole purpose of documentation is to have a complete audit trail in order to reconstruct the trial to ensure that the data is credible and verifiable and that the trial was conducted as per norms(GCP,Protocol etc.)

So far, so good!

And now come our individual interpretations, FDA Folklore, sponsor/CRO specific SOPs and sometimes believe it or not individual wish lists!

Like Vishal puts it, we complicate our trials, increase documentation, add to time lines(more QC checks, QA time, DCF query resolution and all), add to costs(manpower,archival space).

The way out?

We need source notes for all critical endpoints. this would be Medical records and case histories, drug dispensing, informed consent procedures, lab results, IRB approval letters etc, which are not part of CRFs usually, but yes protocol related observations can definitely be directly entered on to the CRFs. The condition that would need to be fulfilled is that this would need to be stated prior in the protocol as per section 6.4.9 of GCP as part of trial design.

Apart from this, the CRF would need to be simple to understand and fill and designed to capture only the essential information related to the trial so as to minimise the need for transcription.

The investigator and site staff would need to understand the importance of ALCOA and be trained on good documentation and record maintainence and retention practices.

There is no FDA regulation or guideline that states that all data in the CRF must be duplicated in another location, or source document.
With the advent of e-trials more and more of source information would be directly entered in to the computer systems and as long as they are 21 CFR part 11 compliant would be able to serve as both source notes and CRF if designed accordingly.

The idea is to think ahead,plan accordingly and design well and thy duplication will be done,I mean down!

I would recommend that you also check out these two very excellent ppt presentations made by Stan Woollen ,who was the director of sceintific investigations at the USFDA and a senior person at the GCP program run by the USFDA.

1.Can less really be more?Source Documentation in Clinical Trials. http://raninstitute.com/PDF_PP_Docs/Can%20Less%20Really%20Be%20More%20ACRP%20April%206,%202005.ppt

2. The facts about Source Documents. www.fda.gov/cder/present/dia-699/wollen-dia99/wollen-dia99.ppt

The poll was reflective of our discussions where majority of the voters did feel that it is alright to capture data directly on to the CRF.However, it is not as simple as that and capturing data directly on to the CRF would require some planning, incorporation in the study design and training at the investigator site before you have data that stands upto regulatory rigor.

And though the CRF may double up as source notes or vice versa,at some places they are both indespensable and the art is in making a science of that!

Will leave you till next time then and hope to keep the buzz alive.

P.S-There are some queries yet unanswered by me and will do so in a while.Todays post is dedicated to the memory of Mom,who was one of the first visitors to my blog ,but would not be coming here anymore.

To you Mom.