Welcome back. In this section, we're going to review the
process of consenting and enrolling volunteers in what I'll refer to as a
stand-alone general screening and recruiting protocol.
So this is a separate protocol, specifically for screening volunteers for
participation in trials. So let me talk about this model for a
minute, this general screening model. In section A, we talked about a beginning
part of it. We talked about pre-screening and that,
that can be telephone based, and you collect some basic information.
In this section, section B of this lecture, we're going to talk about this
general screening with a written consent for screening.
Not for an actual intervention trial, but having this written consent for screening.
And it will involve more than just obviously the phone.
We're going to bring people in, do an in-person visit, and do some procedures,
including some informed consent, physical assessments, and the things that are
listed here with medical history and collection of samples.
This general screening model is very nice in that it doesn't commit the volunteer to
anything more than a health evaluation. So people are calling in and they say, I'm
interested in research and we say, well, we have a screening protocol.
If you'd like to come in and find out if you're healthy enough to participate in
research, we can have you scheduled and you can come down.
Also we have additional trials and they can get information on those trials.
But they can consider those after they've determined if they're healthy.
So the screening model doesn't commit the volunteer to anything more than this
health evaluation. We'll focus just on general screening of
what is healthy. The reason we're discussing this
standalone model is that it doesn't commit that volunteer to anything more than that
health evaluation. If they're healthy, then they can go on
and consider whether they would like to participate in an intervention trial.
But for screening in this protocol, they can just come in, see what it's like, and
make a decision after we determine if they're even healthy enough for
participation. Okay, screening by the numbers.
How many does it take to get a volunteer, get the shot in the arm, as they used to
say? Although vaccines are given in many
different ways. You need to try to have some sort of a
pattern and be able to anticipate that process.
How will that process go? Because when you budget for a trial,
you're going to have to say, oh, it's going to take this much time and this many
people to enroll in my trial. Well, just the screening piece has some
similar pattern. And you need to have attention to detail
for that as well. An individual protocol will provide a time
range for when you can do screening procedures.
So this graphic might be a little confusing, but.
In general, you're going to screen for health status.
A period of time before the intervention. So day minus 56 is an example.
So essentially two months ahead. You can determine if someone has met basic
health criteria. How far out that screening visit will be
will depend on the scientific criteria, or maybe some regulatory criteria of whether
they want some testing done right before you enroll or sponsor comfort of timing of
certain determination of baseline health data.
It's also impacted by the complexity of the pre-screening tests.
So if you're doing certain tests that take a long time, HLA testing as part of
increased screening. You can't do that the day before you
vaccinate. You won't have time to get the results.
So you're going to have to back it up. Think of when you would like to vaccinate,
and when you would want to screen. So these are minuses are days before you
actually want to enrol. And it's a bit of a juggling act to
determine the right time. So you need the right number of people and
you need to be screening them in a time frame.
If you allow too much time between screening and the start of the study, oh,
well, you might have other health factors tha crop up.
They may suddenly have a drop in their hemoglobin and they look like they're
anemic. And oh, you know, 30 days ago, 56 days
ago, they were fine. And how do you sort all that out?
There are some tests that you definitely repeat before you enroll, and one of them
is pregnancy. Because, in the model of phase one, phase
two vaccine trials, we do not enroll pregnant women, until they have been
proven safe in nonpregnant individuals. So you need to think about projected
enrollment time. How long it's going to take you to screen
when you begin to plan your screening timeline.
Okay, So what's involved in the actual screening
process? Well, everything begins with education to
me. You're going to explain the screening
process. When people come in, you're going to have
a consenting. And you're going to collect some
information, such as on this slide, some screening data.
And we're going to walk through a little bit of this in the subsequent slides here.
Protocol explanation is really important, you're going to describe to the individual
who has come in, why they're there. What are you doing?
What is this study? Now in this stand alone idea the stand
alone screening protocol you're going to describe that they're there to be screened
for health and what that means and the kinds of procedures that they will,
The kinds of procedures that they may have done.
When you describe the study, it's possible to do that one on one or it's possible to
do that in a group. And I have to tell you that I love this
picture. This is education under a mango tree at a
trial site in Africa that I went to. We don't have such lovely places to do
education in Baltimore. But you find a place where you can sit
down and explain what it is you're asking someone to consider.
You may use materials such as brochures, charts, videos, and you did develop some
of these materials in your community education assignment.
And I hope that you can see that, that, that can provide value to supplement the
actual informed consent document that you also wrote.
So that combining those, you really get some good education.
So for this screening protocol you would want brochures and information to be
geared towards that screening process. So the screening consent provides
information just about those procedures, and does require a review of the consent
document as in any process. And you may use something called an
assessment of understanding document to go over what the study involves before
obtaining written consent. We're going to give you an example in our
case study in the next section of an assessment of understanding document.
But that's part of trying to give the informed part of consenting.
Don't forget that first word, informed. Consent, it's good to also look at what
consent means. Consent is an agreement by the volunteer
to participate in the protocol. But it's more than a signature.
It's an agreement from you. There are responsibilities that you have
to uphold that are written in that document, as well as the volunteer.
And the consent has to be obtained before any procedures are done.
So this is a refresher from the human subject protection lecture.
You did learn what goes into a consent document but I'm emphasizing here that it
is more than a signature. The signature should be that culminating
event that happens after education. After an opportunity for questions and
before you initiate any procedures. Informed consent is governed by certain
regulations. If you're in the US, it's governed by the
FDA regulations that are found in 21 CFR 50.
It's also governed by the ICH good clinical practice guidelines, which are
outlined in section 4.8. In the informed consent lecture, Amber
went through and talked about elements of what goes in the document.
Why don't we just take a minute here and look at other aspects of informed consent
that are in your GCP book. Which I hope you keep by your bedside for
reading at night when you're having trouble sleeping.
So, one, 4.8.3 says you need to address things like other influences.
So, how are you addressing whether someone is making an informed decision on their
own or are there other influences? And that has a lot to do with vulnerable
population. Are you providing information?
Are you providing it in a way that they can understand it?
Is it just a form or are you communicating?
Is there some need for other pictorial or video or other things to provide
information? Is the information in a non-technical
language? And actually the word that GCP uses,
non-technical language. They don't exactly say that it has to be
translated into your own language, but it needs to be in language understandable to
the volunteer and as non-technical as possible.
It does to me infer this concept of translating.
And then you need to obtain their decision of consent or non-consent prior to doing
any procedures. And as I said, you did learn about what
goes in the document and wrote your consent forms covering A through T.
So. The informed consent discussion has to
happen in a comfortable place where it's non-coercive, where someone can feel free
to ask questions. So before I mentioned the education
process can be done in a group, and you can actually explain what this study's
about. When you actually want to have the
individual sign the consent, you need some private time to have them have an
opportunity to ask questions they may not ask in front of an entire group.
You need to also provide a copy of that consent to the volunteer, and make sure
you review the entire consent with them. Now, we have cases where people decline
taking the consent, To take the consent home.
I did a lot of work, a lot of my years was with AIDS vaccine trials.
And people didn't really want to walk out, even though it was prevention trials.
Didn't wanna walk out with a consent form that said they're in an AIDS vaccine
trial. So you document that they did not wanna
take a copy, and keep their other copy in the, in the file.
But, you are required to offer them a signed copy.
I mention this assessment of understanding tool for determining whether they
understand what's in the consent. And this is something, actually, we began
to do at the center. A long time ago.
About fifteen years ago, when we realized that we can go through it.
And people can say they understand. But it would be great if we could have a
bit more objective way to determine whether they understand the content we
provided. So there are different formats.
You can have true/false, multiple choice, short answer.
And then you can see some questions that are on here.
What you include in the assessment of understanding.
Should be the critical elements of the informed consent.
And you should also explain that it is a document to help us know whether we have
provided the information to you in a clear and understandable way.
It should not be presented as this is a quiz of whether or not you're smart enough
to understand the consent. It should be whether or not the consent's
clear to you. And I think that's very important.
Tests make people nervous. You don't wanna do that.
When do you need a witness? Now this is a question that has come up in
many different settings and in settings where you really have, difficulty in a
highly illiterate population. And some of the studies that we've done in
international settings. In GCP an impartial witness is required if
the subject is unable to read. And at that point the witness must be
present for the entire informed consent discussion.
Have a lot of questions about, well, that's privacy issues and the witness
shouldn't be there to hear information about, you know, the volunteer's health.
That's true. They should not be there for review of a
volunteer's health. But they should be there to determine that
if Karen is consenting, and there's a document in front that has written words
that are saying what the study is about, that witness is saying, yeah, Karen is
saying what's on that paper. So the witness is really just confirming
that oral discussion matches what is on the form.
The difficulty is finding someone who can read if you're in an area of high
illiteracy, and someone who is impartial, that is, not working on the trial.
And we've had lots of discussions about this.
We could actually have followup discussion on the bulletin board if you want, about
how to determine who is impartial. It's a.
There's no one answer, and I think it's something local that people need to
discuss. On this slide I also wanted to mention the
legally acceptable representative. This is needed if the subject is unable to
provide consent. So that's not the witness issue.
The witness's literacy, the legally acceptable representative, is if they're
unable. And what comes to mind is someone who's
disabled, or children. Children are unable to provide consent if
they are not of legal age. And for children enrollment, there is an
LAR or a parent that is required to provide consent for that individual.
Just to make it about language translation.
Gcp doesn't state that consent forms must be translated into local language, but
it's inferred. And here's what it says.
And the language must be understandable to the volunteer, and should be as
non-technical as practical and should be understandable to the subject as, or the
legally acceptable representative. So that sounds very straightforward, until
you start to look at the content of the things that we're describing.
And for many languages, there are not words that translate for some of the
medical language. So it is really a challenge to how to take
an English consent form of any type of medical study.
And translate into another language. It can be really tricky when there are
languages that are primarily oral. And they really don't even have an
equivalent to write for their, their own language.
But you need to do the best that you can for language translation.
And part of that is to document back translation.
That's always a bit of a stresser. So somebody translates it, and then you
need to have someone review it and say, in the local language, yes.
If I look at this in Thai, it does mean the same thing as the English template.
So that is a bit of a process that you have to consider.
Use of things like pictorial aids and other supportive things for consent.
Is I think really the way we need to go. And I know that there have been also some
creative ideas of audio recording consent so that you can actually explain things in
a way that maybe it's not as clear on the written information, but you can audio
tape it and show that you're describing the information in a way they can
understand. Record keeping is important all the way
through a trial. And you have to have a case history for
each individual. Alright.
And you need to record the consent and. And you need to record the signature of
the volunteer and the person who is sx the consent.
So this was covered again earlier in the lecture on human subject protection.
So you sign and date. And GCP does say sign and date.
We really recommend that you add a time. And the reason for the time is that you
want a way to demonstrate that your consent was obtained prior to doing any
procedures. And by timing the consent, and if you
time, say, blood collection. You can see that you did actually obtain
the consent. Before you've collected the procedure.
So it doesn't take that much to add it. You should discuss how you want to do it,
if you're using a 24 hour clock or, or how you'll record the time.
But I think the time really helps you in the end of being able to demonstrate that
you did comply.