So, we clearly
have a lot of challenges in quality management, in clinical
research, and, I think, in clinical trials in particularly.
We have the issue of the case report form versus the protocol.
So, is the case report form collecting items
that are not listed in the protocol to be collected?
Is the case report form not allowing us to enter data
that the protocol says we need to be collecting?
We have issues, sometimes,
with the case report form in the source document.
We'll have information on one, but not the other; they need to match.
We also may have issues within the database in the case report form.
So, the database may not be developed
in such a way that we can conveniently get data out
to analyze in a SPSS or SaaS,
some type of analysis software program.
And then, we clearly have, you know, the whole regulatory compliance
issues, really understanding the regulations and understanding
the guidances which help us to adhere to the regulations.
I think sometimes we don't always remember that
they're there and they're intended to help us.
So, Kleppinger and Ball actually
came out with an article several years ago -- it's in the references
-- that talk about a quality system components.
And so, they talk about that all research personnel
need to be knowledgeable about regulations
and about guidances, including ICH GCP, as well as what internal
or institutional organizational policies and SOPs there are.
And I think that sometimes this
may not be as stressed in education
and training for not as much
the directory search team, but maybe for direct care nurses
who might be in an infusion
unit that are giving an IND product.
Do they understand what human subjects protection is all about? Do
they understand that we have laws around
clinical research and clinical trials?
We need to appropriately delegate responsibilities
and that does include responsibilities associated with a license.
So, who's allowed to dispense medication?
What's the definition in the state for dispensing medications?
And what is going to be the plan to have coverage?
Because people go on vacation, people get sick.
So, what's that coverage plan going to look like?
Do you have policies and procedures?
Do you have them at an institution level?
Do you have them at a clinical trials office level?
How is the protocol going to be reviewed?
How are biologic samples going to be handled?
What is the data sharing responsibilities or the data sharing policies?
How are we maintaining human subjects protection?
What is human subjects protection training look like?
What are maybe some of the data management associated responsibilities
in terms of quality control and quality assurance?
And then, what are procedures for reporting scientific misconduct?
And then, do you need to have protocol-specific SOPs
in a manual of operations, which can be very helpful,
especially if you're doing multisite clinical research studies?
In terms of training, again, not just about human
subjects protection, but also about GCP, the clinical practice.
Also, if it's
an investigational product, or if there's a particular instrument
that is being used, or a specific EKG machine that the sponsor
has given the site to be used,
how is training occurring related to that?
If it's administering some type of a patient reported outcome,
some type of a pro tool, are there survey administration instructions?
How are people being trained so that the tool is being administered
the same way at a site or across sites,
again, if you have a multisite trial?
And then, how are you documenting that training?
There's also issues
related to the handling of documents, standardizing data collection
through the use of common data elements,
as well as standard case report forms.
Also, what are you going to be doing for archiving?
So, we have regulatory retention requirements and certainly within the
NIH intramural community, we have NIH policy on records retention.
So, do we know what those are?
And what are our SOPs in place to ensure that we're adhering to those policies?
And then, how are we securing our files, whether they be paper or electronic?
How do we restrict those to only the appropriate individuals who can see them?
How does that all occur?
There's all things to think about, again, quality management.
In terms of corrective and preventive action,
you want to be able to identify potential or real problems
and take action to prevent them and to fix them.
So, develop this CAPA plan.
And you want to be able to document that whole process because, again,
it's not meant to be punitive; it's meant to adhere to our standards
of excellence related to quality data and human subjects protection.
So, ask yourselves some of these questions.
Are protocols written clearly
so that you're not deviating from them, you can follow them?
Do you know what and when procedures to be implemented?
Are staff checking their own work?
Are you relying on someone else to do it?
I actually had the experience of having a research nurse coordinator --
so, study coordinator who's a nurse -- actually say that
that was the sponsor's responsibility
to do the monitoring of source document against case report form.
And I said, "No, that's really everybody has responsibility with quality control."
Does the organization have a quality management plan,
some type of QA plan, monitoring plan, whatever you want to call it?
Does the organization have a way to get a snapshot
of what's going on in the area of clinical research?
Do you have clinical research SOPs?
How are case report forms developed?
Is that something that the research team is responsible
for, the organization, or are they generated by the sponsor?
And do you know what to do
if you have a quality inspection at your site?
So, if the FDA comes in, do you know
what your organization's procedures are is one example.
So, a few resources.
The National Institute of Dental and Craniofacial Research has a toolkit,
and quality management is part of that toolkit.
They have several checklists available for source documents,
the regulatory files that I had talked
about in terms of what to review.
Also, the NCI has AccrualNet.
And if you use the search feature in the upper righthand corner
and type in "quality management," "monitoring," "auditing," you'll get some
various references to either articles, or checklists, tools, things like that.
And then, internationally, the U.K.
has a clinical trials' toolkit.
And if you go to the website and click the Get Started with the Roadmap,
you'll see part of their roadmap is trial management and monitoring.
And there are more resources available if you just search quality management
in clinical research,
monitoring, auditing, and clinical research, or clinical trials.
And there are a lot of references out there.
There's also, if you don't have SOPs,
there are a lot of SOPs that seem to be available online.
You can get a feel for what might need to be developed
in a clinical research organization or a clinical trials' office.