Okay, this is Dr. Bob Wilden.
I am doing a quick demo
on the Clinical Pharmacogenomics Implementation Consortium
and their website, which is very useful
for looking up information that is clinically useful
with regard to pharmacogenetics, pharmacogenomics
or as we say, drug gene interactions.
So I'm going to stop my video and talk about the screen
and basically walk you through the site
and how to look things up as you need them.
Okay, so we are sharing screens.
So this is the homepage,
which is at cpicpgx.org.
Very simple to remember.
CPIC is the Clinical Pharmacogenomics,
Implementation Consortium, and you can read more
about the organization there.
Basically they're here to provide guidelines
and evidence assessments on drug gene interactions
and their usability and recommendations
for use once you have the genomic information
in clinical prescribing.
So there are several rubrics along the heading here,
and I'm gonna click on into guidelines.
So the guidelines are designed as it says,
to help clinicians understand,
how test results should be used to optimize drug therapy.
They're not designed
to tell you whether a test should be ordered.
So there's a significant gap there.
So you have to understand this as
if you have the information,
this isn't how you may wanna use it.
If you don't have the information yet
and you're trying to decide whether
or not to do the test, CPIC is not about that.
All right, so guidelines are here.
They're all published in peer-reviewed journals
and there are links within this to find them.
So there is a search box here,
so I'm gonna put in clopidogrel
and very quickly, CYP2C19 and clopidogrel pop up.
And so I'm gonna click on that
and I get a webpage that gives the guidelines.
It has a link to a PDF of the published paper
which goes over the guidelines as published in 2013.
And there's the next line is, updates since the publication.
So in March 2017, it gives an update on what happened
at the FDA and tells that the FDA level didn't change
and the recommendations don't change.
So there are really no changes to the recommendations.
There are tables
and figures in the main manuscript which are listed here.
These tables in the manuscript are actually,
really quite good.
And if you wanna sort of jump ahead in your process,
if you're in a hurry, you can open these manuscripts
and jump to the tables
and get a pretty clear picture of what you need
to do in a particular situation quite quickly.
There's a supplement here
which has additional information that's linked.
The tables and figures are listed in this table
below from the supplement,
and they include allele definition tables
which most people don't have to deal with,
allele functionality table, allele frequency table.
These are things that are useful for people
who are designing tests
and trying to apply them to populations.
But this is where one generates the information
that comes out of a genotyping test
and translates that step by step into a recommendation
into a metabolizer status
and into a recommendation for prescribing.
So there additional links down here
that you may be interested in, but basically the bulk
of what clinicians are gonna be interested in is up here
at the very top, this paper
and potentially the linking into the tables, all right?
So I'm gonna just open this
and I'm gonna make sure that I am sharing that as well.
Okay, and so here's the paper as it looks.
The CPIC update
and it gives information about it, gives background,
gives genotype phenotypes.
So here's the phenotypes associated with the genotypes
and examples of the diplo types that maybe you commonly see.
And as I scroll down,
then there's therapy recommendations based
on the CYP2C 19 status when using clopidogrel
for the acute coronary syndrome, PCI patients,
which is the patient group
for which the protocol guidelines have the most data
to support using the pharmacogenomics in practice.
So that gives you the strength of the recommendations
and the therapeutic recommendations, given the genotypes
and the phenotype of metabolizer status.
All right so there's lots in these papers.
This one has an algorithm for suggesting clinical actions.
And these are really well written and worth digging into
if you are gonna be using these drugs
and the pharmacogenomic test data on a regular basis.
Or even irregularly, you can come to here
and find the information that you're really looking for.
So again, going back, here are the guidelines.
For this one, you get there by going to guidelines,
put in your drug of choice or your gene of choice.
And so for example, if I put in CYP219,
I can see that there are actually multiple drugs
or drug classes for which CYP2C19 has recommendation
or has guidelines in in CPIC.
So it's a very, very, you know, useful approach.
Up here at the top on the menu, again,
we're gonna look at the gene drug list.
It's kind of similar but it's kind
of a more feature rich list.
So if you're only looking for the guideline,
that first rubric is the place where you wanna go
if you wanna get a little bit more rich information
about it, so let's just stick with CYP2C19.
And you don't even have to click enter, it just pops up,
fills up the table and here,
you have your different gene drug pairs.
Again, a link to the guideline that takes you back
to the same place we were before.
There's a column for the CPIC level which is the level
of the evidence and the level of strength
and support for the guideline.
So these are all level A,
which means the CPIC organization feels strongly
about the validity of those guidelines.
And CPIC level B are ones
that have a little bit less evidence
or a little bit less strength.
And some of those are labeled B,
but don't yet have guidelines written
because they haven't gotten around to it.
For example, those are coming bit by bit.
There's some down here with CPIC level C
and the definitions of the levels are available
in here on the second link.
So here's CPIC levels for genes and drugs.
So the definitions of A, B and C are in there.
The next column is pharmGKB levels of evidence
which starts with one A, two A, three, et cetera
and it's a different kind of level of evidence thing.
And you can go to pharmGKB,
which is linked in here somewhere,
to get a better picture of what those levels
of evidence are.
Those are basically more the level
of evidence relating to the analytical validity
and the clinical validity, not the clinical utility
of those particular drug gene pairs.
PharmGKB also has all the background literature linked.
So if you're really interested in one particular area,
you can go to pharmGKP
and pull up all the literature that's known about that
and that's very helpful.
The next column is, what is the pharmacogenomic category
when you look at an FDA label for that particular drug
and that's on the FDA website.
We're gonna talk about that a little bit too.
So the FDA label has these kinds of things.
There's actionable, informative, there are other labels
as well which are not shown here
which may be like a black box warning,
something that's really,
really important to pay attention to.
So you can play around with this and add other other genes.
G6PD has a guideline for rasburicase
and for example, the FDA label says that testing is required
before you give rasburicase because the risk is quite high.
If you have V6PD deficiency, you will really wanna know
that before you give rasburicase.
All right, so those are other examples here.
Okay, so there's additional things here.
So if you're interested in looking at this
from a geneticist level,
you can look at the specific genetic variant.
So this is a protein variant, this is a CD NA variant here.
And you can look those up in the same search mechanism
and see if there are guidelines
for those individual variants.
So these are the guidelines that refer to Ivacaftor,
for example, for CFTR, okay?
So that's a really nice way
to look at it in even a more different way.
There's a big list of publications here
that you can dig through.
CPIC has meetings if you are a pharmacist, pharmacologist
and somebody who knows a lot about this who wants
to participate in CPIC, you can join in meetings,
additional resources, working groups members
and contact for the organization.
But really, you know, the meat of what we wanted
to talk about for the purposes
of this little walkthrough is the guidelines
and the genes and drugs and alleles, things.
Thanks for listening to that.
I will now go to the fda.gov
and I'm gonna search for biomarkers table.
And here's the table
of pharmacogenomic biomarkers in drug labeling in the FDA.
And I'm just gonna double check
that we're still sharing the right bit here.
Yep, we're on the main screen so we're good.
And so this is an FDA US Food
and Drug Administration website.
So drugs which have biomarkers associated with them,
that is measurements you can make on blood,
DNA, urine, other things that help advise whether
and how you should use that drug.
That's a biomarker.
And those biomarkers are part of the FDA approvals
for a great number of drugs,
and that's what this table lists.
So here we're calling abacavir, there's an HLAB biomarker
because there's a boxed warning
as Abacavir in certain HLAB types,
can lead to life-threatening adverse reactions.
We've talked about the antidepressants
and they're saying precautions.
So there may be some things you can learn from CYP2D6
that you may wanna take precautions.
And there are other kinds of things.
Here's clinical pharmacology.
Just, you need to know that UGT1A1 is involved
in the elimination of arformoterol, for example.
So there are different levels here, down here,
warning and precautions.
So there's different levels that you need to be aware of.
You can link on this, on the individual drug name
to get to the drug labels.
You can also download the detailed version
of this table, which has the labeling text in it.
And I won't do that at this point,
but you can download that.
This table is updated every time a drug gets updated
in its biomarker information
or the level of warning that the table gets updated
whenever a new drug is approved
with a biomarker attached to the approval.
So this is a really good place to look
and it's basically one long webpage,
so you can do a control F on the webpage
to find the medication that you're interested in
or the genes that you're interested in.
That's the way to search this page, okay?
So down to the bottom, warfarin, et cetera.
So I'm gonna stop there.
Those are two websites
which are really extraordinarily helpful
in looking up authoritative information on what
to do with pharmacogenomic information.
Thank you and thank you for learning.