So, let's talk
a little bit about actually managing the data.
It really becomes a system that is a continuous system.
You know, the data's collected according to the protocol.
Hopefully, there's some internal quality audit or checkpoints at the site.
The data is submitted according to the protocol.
It's reviewed at the data center where queries are often
generated, can be generated.
We'll talk about that.
And then data's corrected and resubmitted.
And this is kind of just this ongoing cycle of data submission.
And I think this says, the picture says a lot,
but just going to give an example for a phase III trial.
There are probably close to 7,500 to 9,000 pieces of data
that might be collected for a single patient.
And so, if you take that times a study that might have a sample size
of 500 patients, that's going to be over 4 million pieces of data.
So, kind of gives you a perspective of the amount of work and the importance
of collecting accurate data when it comes to that level of effort.
So again, I want to talk a little bit about the investigator responsibilities
as far as relating to completion of the CRF.
The good clinical practice, or GCP, guidelines
really specifically state that the investigator should ensure
the accuracy, completeness, legibility, and timeliness of the data.
And that would include that all sections are completed,
any alterations have been properly made, and all adverse events are fully recorded,
and they are reported accordingly to regulatory bodies.
So, timeliness is very important.
I deal -- I feel, and I try to really encourage my staff,
to complete the data forms as closely after the visit as possible.
This is where you pick up on maybe something was missed.
Maybe you know
it took place, and information was stated, but it wasn't documented completely.
You're going to remember, they're going to remember to complete that
and know the information, or record it, closer to the visit than if a staff person
is waiting to go back in three months later and fill out that data form.
It's a little too late to capture the information that might have been missed.
It also ensures
that the information can be retrieved or followed-up
on while that visit's still fresh in their mind.
There are problems that are encountered when CRFs are completed
and this is very common.
Sometimes they lack -- there might be a lack of source documentation.
I think one thing that we continually found in our site
were physicians failing to report in the source document
what the patient's actual performance status was.
Simple, but often our auditors required that number
instead of just a description of the activity of the patient.
It was a frustrating event.
So we developed actually a source document
that captured that, so we could have the information.
There can be errors in the protocol, adhering to the protocol,
there can be missing data, transcription errors, lag in data entry,
poor patient recall after adverse events, and also just patient poor compliance.
Queries are a day-to-day activity.
If you've been involved in clinical research
much at all, particularly as a research associate
or a CRA, a research nurse, they basically review the,
you know, they -- reviewing the activity within the data that's collected.
It helps to clean the data, and it helps to assess
and resolve some inconsistent data, missing or range
discrepancies, deviations from the protocol.
And very commonly sponsors will generate what we call data clarification
forms, or DCFs, and they're sent to the investigator for resolution.
Again, this is more probably common with the paper forms
than the electronic because, as I said, electronic forms
-- the opportunity to collect or to clarify and correct issues
is usually provided at the time of data entry, but not all the time.
I really hope that any research sites do
have as some sort of an internal process to review their research
before they have an external auditor come in.
To wait until that external auditor comes in to find
your problems is not a good idea.
To be proactive, self-identify your errors, develop corrective actions
plans, correct your SOPs, or update your SOPs,
and then -- this is just really key to preventing non-compliance.
And it helps to then train your staff more appropriately, as well,
so hopefully those issues are resolved at the time and aren't ongoing.
Just a little bit on data safety monitoring boards
because I see in your agenda all your topics
for discussion that there is a discussion on data safety monitoring boards.
But I think it does play an important role
when you're talking about data management.
The data safety monitoring boards are basically boards that are made up
of experts that, for specific usually disease categories, that review
trial data, and look at accrual rates, they look at adverse events
that have been occurring, and they also look at the data reports
as far as what is the interim analysis showing.
They also then by doing that might capture issues for trials
if the accrual rate really slow, they're really going to encourage
that investigator to figure out why, develop methods, or look at what
the problems might be, perhaps an amendment needs to be made
to the study to change something in eligibility that's prohibiting accrual.
They look at adverse events.
If one arm, it's a two-arm study, and one arm is more toxic than the other,
the data monitoring board might suggest, depending on how
severe those differences might be, of shutting down
one of the arms, or even shutting down the study.
And doing the interim analysis also helps to
assess is one arm possibly giving better results.
Are patients -- and they usually write this out in their data analysis
plan of what they will accept as a level of change between arms.
If one arm has reached that threshold, they may actually shut a study arm down
and continue maybe the other arm or shut the study down itself.
So, the data safety monitoring
boards really do play a key role in assessing trials.