So, like I mentioned, safety is the primary imperative of Phase 1 studies.
And when you do a Phase 1 study, there are certain standard safety measurements
that you will always do, okay. So, you will always.
To a physical examination you will do laboratory tests.
So, you, you want to look if there isn't any changes in blood electrolytes, any
changes in blood counts, any changes in patient's liver function or kidney
function. So, there is standard hematology, serum
chemistry, and urinalysis test that you will do.
You will look for vital signs, okay, you will look at blood pressure, you will
look at heart rate and pulse rate, and so forth.
And then you will look at ECG assessments for cardiac function.
And then you will also do adverse event monitoring.
And what, I'll come to you in a minute. Adverse event monitoring is quite simply
literally asking a subject, you know, how are you feeling?
You know, because people in such a setting might not feel very emboldened to
say you know, I kind of have a you know, pain in the back of my neck.
Or, you know, I, I feel really hot, or you know, whatever.
So, you have to very proactively ask people if they're having any adverse
events. I'm sorry go ahead.
>> what do you do in terms of screening people who already enrolled in previous
Phase One or clinical trials in the past. >> Yeah.
So, we'll come to that. We typically when you write a protocol
for a Phase One study we have criteria. Entry criteria.
And one of the entry criteria always says that you should not have participated in
another trial or donated blood or a whole bunch of things, you know, up to x days
before. The, you know, day one of this particular
study. >> Do people generally like.
>> Yes. There are, there are, professional
participants to Phase 1 studies, yes. >> It's a. [LAUGH].
>> IE college students. >> IE college students, yes.
So, yes, very often, they. Because, because you're looking for
reasonably healthy subjects who have. You know, pretty well defined body
weights or who have a pretty well defined age range.
And, you know, students tend to, tend to be a good, good they fall in that
category. Yes.
>> I know you're focused mainly on talking about Phase 1 studies.
But obviously, safety carries out. >> Mm-hm.
>> In all the phases. So I know there's always concern with
under reporting and over reporting. >> [CROSSTALK] Mm-hm.
>> And there's a lot of patient-driven systems for to help the research subjects
to report their, you know. >> [CROSSTALK] Mm-hm.
>> [INAUDIBLE] data. So, how is that being dealt with, what,
what. >> So, there's tremendous regulatory
scrutiny right now, to make sure that when you're doing a study.
There's absolutely no under-reporting. So, very often we err on over reporting
instead of under reporting. our protocols get reviewed by ethics
committees, by institutional review boards, before they get approved.
they get reviewed by, you know we submit them to the FDA.
and, and you need to demonstrate that you have the right.
Tools in order to capture adverse events that you know, if, for example, if you
give a drug and let the patient go away, you know, go home two hours after you
dosed him and you don't bring him back or ask him any questions until seven days
later. That's going to be suspect because you
know somebody might have had a bit of a rash but it went away after three hours,
they never reported it. So you need to demonstrate that when you
were doing your study, you had the right mechanism, you timed your, your, your
collections, you timed your, your monitoring and your questioning for
adverse events frequent enough that you, you, you did pick that up.
So obviously, when you're writing this, this, this Phase 1 study protocol you
need to be very careful how to time all of these assessments.
So a great example might be. you know I, we, we, I worked for about
ten years on a compound we just got in the market, it's an anti-androgenic drug
for, for renal cancer. all of this, this class of drugs, they
all cause an increase in blood pressure. That, that, that's a side effect, they
cause an increase in blood pressure. It typically might happen about two to
four hours after you give your, give your first dose.
Well, if I'm doing vital signs. Right before dosing, half an hour after
dosing, one hour after dosing, six hours after dosing, eight and 12 hours after
dosing. I'll have completely missed picking up
the blood pressure increase and the patient won't be symptomatic for, you
know for, for most likely, you know, the blood pressure will go up, but you'll
never pick it up. So you need to be very careful when you,
when you design your protocol based on what you know about the compound, based
on what you know about other drugs in the same class.
That you have, that you time these measurements very carefully and for
example, when we got these protocols, the exact timing of the ECGs, the vital
signs, the blood, the blood pressure reporting that goes through tremendous
scrutiny and people make sure that you haven't missed any opportunity for
missing a drug related effect. in addition to those standard safety
parameters, you make, you, you often will include additional safety measures.
And, and what drives these additional safety measure measures?
Usually what you know about that compound.
Right? So if I know, for example, that the, I,
I, you know, I have a, a brand new target.
This is the first drug that has been developed against this particular target.
But you gave the drug to animals and you noticed some kind of ocular toxicity,
okay? In a typical Phase 1 study, nobody's
going to measure visual function, okay? Nobody's going to do any kind of ocular
examination. But if you've seen this in your animal
studies, then in your Phase 1 study, it is your imperative to make sure that you
have the appropriate. Ocular testing, whatever is necessary,
included in your study to, to characterize that for the compound.
Okay. Fairly.
Makes sense. Fairly, fairly obvious.
if you know that your drug, for example causes changes in you know, the left
ventricular ejection fraction volume. Okay, then you might want to include MUGA
scans in your Phase 1 study. So, depending on what you have seen in
your animal studies, depending on what you know about the class of agents, you
would build in additional safety measurements in your Phase 1 study.