This video guidance represents OHRP's current thinking on this topic at the time of production
and should be viewed as recommendations, unless specific regulatory requirements are cited.
The use of the word "must" in OHRP guidance means that something is required under HHS
regulations at 45 CFR Part 46. The use of the word "should" in OHRP guidance means that
something is recommended or suggested but not required. An institution may use an alternative
approach if the approach satisfies the requirements of the HHS regulations at 45 CFR Part 46. Hi,
Dr. Mitchell. Thank you so much for taking the time to meet with me… is this still
a good time for us to talk? Absolutely! Thank you. I just had a few questions that I wanted
to go over with you about this protocol that I am about to submit to the IRB for review.
Sure, no problem. And by the way thank you very much for dropping it off yesterday
so that I had a chance to go over the protocol and the informed consent document. I looked
at them last night. What can I help you with today? Well, as you know, this is a randomized,
double-blind, placebo controlled study of the effects of Memoride on the cognitive function
in subjects with schizophrenia. The purpose of this study is to test whether Memoride
improves the memory. Subjects with schizophrenia will be admitted to the hospital for approximately
two weeks. During the first week of the study, subjects will undergo a physical exam, psychological
and cognitive testing, and an MRI of the brain. During the second week of the study,
subjects will receive either Memoride or a placebo three times a day for seven days.
Also during the second week, they will be doing an extensive series of cognitive tests
to help us establish whether or not the subject’s memory is improving. They will also receive
a second MRI at the end of the second week. Tell me, will subjects need to come
off of their medications to be eligible for this study? As you are well aware, taking
someone with schizophrenia off of their medications could potentially make their symptoms worse. Right.
Actually no, we will not. Memoride will be added on to their current medications. So,
my question is, as the study will be focused on subjects with schizophrenia, and a main
symptom of their disorder is psychosis and/or a thought disorder, if subjects are unable
to give informed consent, what are my options? Well, let's just take a look at the
regulations here. The regulations specifically state that “no investigator may involve
a human being as a subject in research covered by the regulations unless the investigator
has obtained the legally effective informed consent of the subject or the subject’s
legally authorized representative.” So, one option is that if you felt the subject
could not give his or her own consent, you could discuss with the IRB the possibility
of having the subject’s legally authorized representative give consent. If I did
it that way, I think I would include the caveat that should the subject regain or develop
their own capacity to consent, then his or her consent must be obtained for any further
research. That's a great idea and that certainly makes sense. So, it sounds like
you would want to come up with a way to determine if a subject has the capacity to give informed
consent. Now perhaps this is something you could consult about with some of your colleagues
with respect to options for dealing with that issue. If subjects are found to be unable
to give their own informed consent, you could either have their legally authorized representative
consent for them, or another option is you can decide that if they do not have the capacity
to give their own informed consent, that they simply could not participate in the study.
Now of course if you chose to exclude subjects that lacked the capacity to give informed
consent, you would want to consider if that would affect the overall validity of the study.
You and your team should think about what would be most appropriate, present it to the
IRB for its consideration, and then of course the IRB would make the final determination
in that regard. OK, well those are both really good ideas, thank you very much. Are
there other aspects of the informed consent that I should be mindful of? That's an
excellent question, and the answer is yes. The regulations state that prospective subjects
or their representative must have sufficient opportunity to consider whether or not they
wish to participate. OK, well I plan on sending the informed consent document to
prospective subjects prior to meeting with them, and of course will give them ample opportunity
to ask questions and to think about whether or not they would like to participate when
I meet with them in person. OK, that sounds great. You also want to ensure that
the possibility of coercion or undue influence would be minimized. And, as you know, the
informed consent must be in a language that is understandable to the subject or the representative,
and there can be no exculpatory language used in the consent. OK, well I'll be sure
to double check the informed consent process to make sure that it meets these requirements.
Thanks so much for taking the time to meet with me. It was very helpful and instructive. Oh,
it's been my pleasure, and please feel free to stop by anytime. Have a great weekend.
You too. Take care. Hi, Mr. Smith, thank you so much for coming in today.
I wanted to spend a little bit of time talking to you about your possible participation in
the study. Well, thank you for inviting me, Dr. Presley. I’m glad to be here. Sure.
A few weeks ago I sent you a copy of the informed consent document. Did you receive it? And
if so, did you get a chance to read it? Yes, I brought it with me. I did get a chance to
read it over when I got it in the mail, thanks. Great. Did you have any questions about what you’ve
read so far? So far I think I'm OK, but I might have questions as we go along. OK,
that's totally fine. The first thing I would like to emphasize is that the informed consent
process is actually a process. It’s not just having you sign this document today.
This means that we will be providing you with information throughout the study, and that
you should always feel free to ask questions at any time, even after the study is over. OK,
that's good to know. OK, well let’s get started then. Although I know that you’ve
already read the informed consent document, I am going to go over it again with you to
just be sure that we all feel comfortable with what has been explained to you, and that
all of your questions have been answered. And then at that point, you will have the
opportunity to take all the time that you need to decide whether or not you would like
to participate in this study. OK, that sounds good. First of all, we want you
to understand that this study involves research. Research is very different from the clinical
care that you receive from your regular psychiatrist in the community. Your regular doctor is treating
you and is giving you care based on known scientific facts. In this study, we are asking
a question that we don’t yet know the answer to. Well I think I understand that because
I met with my psychiatrist before I came here and he explained that to me. OK, great.
Well, now I’d like move on and give you a little more information about the study.
The purpose of this study is to see if Memoride improves memory, the ability to concentrate,
and problem solve in people with schizophrenia. That's great, because I sometimes have
problems with those symptoms. I have trouble with concentrating sometimes, I have trouble
with my memory, so it would really benefit me a lot to be in the study. Well again,
we don’t know if this will work or not, and that’s why we are doing this study.
We don’t want you to have the misconception that this drug is going to improve that problem,
because at this point we don’t know whether it will or not. Although you may not benefit
from this study directly, you will be contributing to determining if this drug improves cognitive
abilities in people who have schizophrenia. Well I guess even if I don't benefit,
then it I'm glad that other people might benefit who have schizophrenia. So, that's a good
thing. Well, we appreciate that. As you know, this is an inpatient study, which means
that you will be staying in this hospital on the research unit while you are in the
study. The study will last for approximately two weeks. We do realize that two weeks is
a long time to be in the hospital, but as long as your symptoms are under control and
that we feel that you are safe, the staff will take you off the unit during the day
to participate in a variety of activities. That's good to know. Will there be any games or computers
on the unit for me to use? Actually, yes. There is a computer and a TV with some
video games. OK, good, because otherwise I think I might get a little bored because
it's two weeks. Very understandable. OK, so let me move on and tell you a bit about
the study design. This study is called a “double-blind placebo controlled study.” I realize that's
very much of a mouthful, so let me try and break that down a little bit for you. Do you
know what a placebo is? Isn't that like a sugar pill, or a fake pill, or something
like that? Right, that’s about right. The placebo pill will look the same as the
pills containing Memoride but it won’t have any Memoride in it. The second part is the
"double-blind study" part, which means that neither you nor the research team will know
if you are taking the study drug or the placebo. This is a very common type of research design,
as it helps the researchers avoid being biased when assessing study subjects. Right,
but that's kind of scary. Will anybody know if I'm taking the drug or not? Definitely,
yes. The pharmacist will know, and if there is ever any problem, all we need to do is
call down to the pharmacy and they can “break the blind,” which means that they will tell
us if you are on the study drug or not. And if that happens, will I then have to come
off the study? Yes, actually, once the blind is broken we would take you out of the
study. I see. So, finally, let me explain the last part of that, which is "randomized."
Let me explain what randomized means. Well, I think I know what that means already. Isn't
that like when you flip a coin, so I might either go on the drug if I get heads, or tails
I might not go on the drug and get the placebo? Exactly! So you're going to have a 50-50 chance of
being on the study drug. So let’s move then and talk a little bit now about
what procedures you're going to partake in if you join the study. Once the study begins,
you will be asked to take some psychological and cognitive exams that will test your ability
to pay attention, problem solve, and remember things. During that first week, you will also
have an MRI of your brain as well as a physical exam. In the second part of the study, the
second week, you will be given either Memoride, or a placebo that looks like Memoride, three
times a day for seven days. OK? OK, so will I still be on the medicications that
I'm currently on, or will I have to come off of those. No, you will still continue
to take your medications that you psychiatrist already put you on, and the Memoride or the
placebo will be added on to those medications. So, moving along, you will also be given
some more cognitive tests as well as a second MRI towards the end of the second week. Two
weeks after you actually finish the study, we will call you at home to follow up with
you to make sure that you haven’t had any additional side effects or problems, and to
answer any additional questions that might have come up for you at that time. Do you
have any questions about what I have told you so far? OK, this sounds really great
but I'm wondering that if the drug really works for me can I get the drug when I go
off the study? Can I start it up again? We would welcome you to share the results of
the study with your personal psychiatrist so that together, you can make an appropriate
decision regarding your care. Do you have any other questions at this point? Well,
I'm kind of worried about insommnia, because sometimes I have trouble sleeping. Is this
one of the side effects of Memoride? There are a number of risks from participation in
this study, which include possible side effects from Memoride. The side effects that have
been reported for this medication include nausea, vomiting, and the lack of appetite.
Insomnia is not a known side effect, but it is possible that you might have a different
reaction to it that is yet unknown. There are a few other possible risks from participation
in the study. As I mentioned, you will be doing some cognitive testing, however this
will be done at a relaxed pace, but it’s possible that taking the tests may produce
some discomfort from you feeling anxious or nervous. These tests can usually be completed
in about 75-80 minutes, and if it becomes too difficult, we can stop. OK, what
about the MRI. Isn't there risk associated with the MRI? There are some minor risks
associated with getting an MRI. For example, you will be asked to lie on your back for
about an hour, and it may get uncomfortable for you to lie still for that long. In addition,
the MRI machine makes a lot of noise, but we will give you some ear plugs that will
hopefully help with that. Also, some people get claustrophobic from being in the MRI scanner.
Do you know what claustrophobia means? Yes, I think so. Isn't that like when people freak
out if they're in really tight spaces? Right, that’s correct. Some people get very anxious
or might even have a panic attack. Has that ever happened to you? No, that's never
happened to me, so I think I'm OK. That’s good to hear. Also, because an MRI is a very
large magnet, it has the ability to move or attract metal. So before you enter into the
room with the MRI scanner, we would ask you to remove all jewelry, and if you have any
metal in your body (like metal plates, or shrapnel, or a pacemaker, for example), we
would not allow you to have the MRI, as it could place you at risk. Got ya--well,
I don't have any metal in my body, so I should be fine. Good, thanks for letting us
know that. As I mentioned earlier, you will have a full physical exam before participating
in the study, so we will go over your entire medical history in order for us to know more
about your health. I also wanted to mention again that participation in this study is
not designed to benefit you directly. However, the information that we learn from the study
may help people with schizophrenia in the future. Yes, I understand that. What
happens if I decide not to participate? Well, one alternative to participating in this study
is not to participate. Also, not participating or withdrawing from this study would not exclude
you from possibly participating in other studies that we have or from things that you would
otherwise be entitled to, such as medical care. So, will my psychiatrist or any
one of my family members be able to review my research records? No. All of your
information will be kept confidential, unless you request, in writing, that the information
be released to a particular person or persons. Well, I think that sounds pretty reasonable.
I do have one other question. I noticed somewhere in the informed consent that there was something
about getting payments for participation. Can you talk a little more about that? Sure,
yes, there is a small amount of compensation, which will hopefully cover your transportation,
and some other minor expenses that you may incur from participation in the study. Besides
these costs, we don’t foresee you having any additional costs associated with the study. So
how much will I get? The compensation is broken up into 3 parts. For the first week
of the study, you will receive $50.00. For the second part of the study when you will
be getting either the study drug or the placebo, which again I mentioned is a sugar pill, you
will receive $150.00. And if you get the MRI scans, you will receive an additional $150.00.
So, if you complete the entire study, you would get a total of $350.00. OK. Well,
that doesn't sound like a lot of money, but I guess I'm really doing it for different
reasons. Well, we appreciate that. Also, I wanted to inform you that if you do sustain
an injury during the time that you’re participating in the study that is related to your being
in the study, we will provide short-term care at no cost to you. Does that include
anything that might happen if I have side effects from the medication? Yes. It
includes any problems you that have while you’re in the study that are related to
your participation in the study. Also, if you do have any problems, it’s really important
that you immediately let the nurses or the doctors know. There are nurses on the unit
24 hours a day, so someone will always be there to help you. In addition, if you need
to reach me, as you see here on the consent form, there's my phone number and my pager
number. So I can call you at any time? Yes, definitely. Separate but related, you’ll
also find the name and phone number of the patient advociate, the Subject Advocate. Feel
free to contact her if you have any questions or concerns that you don’t feel comfortable
talking to the research team about. Is she really nice? She is very nice, she
is. Do you have any questions? I think I'm very interested in participating in the
study. It's something that I think is going to help other people, and I'd really like
to help out. OK, I know I told you this a few times already, but I just wanted to
remind you that participation in this study is entirely voluntary, and that you may choose
not to take part, or you may end your participation in the study at any time, and there would
be no penalty for doing so. And I want to emphasize that withdrawing from the study
would not make you lose any benefits to which you are otherwise entitled. OK, that
sounds fine. There was one last thing I wanted to mention that is related to withdrawing
from the study. Not only can you stop the study at any time, but I can stop it too.
So, for example, if your symptoms worsen to the point that we feel it is no longer safe
for you to continue in the study, we would withdraw you from the study at that point.
Or, if we get information about newly discovered side effects from the study drug, we may stop
the study then too. It's important that you know that your safety is always more important
than the research. Well, It's good to know that you're looking out for me, so I
appreciate that. Sure. Well now that we’ve gone over the information about the
study, have you made a decision about whether you’d like to participate, or would you
like to have some more time to think it over? I think that I have had enough time. I would
like to participate. I think it would be very interesting and I think it would be helping
other people out. So, I would like to. Great, well we very much appreciate your willingness
to be part of our study, and again, at any time if you change your mind, just let us
know. So, since you’ve read over the consent form and if you have no further questions,
I’d like to ask you to sign the document. And as a reminder, signing the informed consent
document is acknowledging that the information in the consent form has been explained to
you, and that you have been given the opportunity to discuss it and ask questions, and that
you do, indeed, consent to take part in the study. OK, so where do I sign? Right
here, and here's a pen. Great. Again, I want to thank you for agreeing to be a part
of this study, and I very much look forward to working with you. I think it will
be interesting. Thanks, thanks alot. I’ll be right back. I’m just going to go make
a copy of this consent form for you. OK, I'll wait.