News on Youtube Oct 1 2017

>> Martin Blaser: Welcome back.

The rest of today's agenda will be dedicated to discussing the report of recommendations

from the three working groups on incentives.

And I'm going to show a couple of slides to provide an overview about this.

So, the title of the work that we're doing and the report that we will be soon voting

on involves recommendations for incentivizing the development of therapeutics, diagnostics,

and vaccines to combat antibiotic resistance.

Let me provide an overview of our working group activity.

Our overarching task was to address the best way to incentivize the development of therapeutics,

anti-infectives including alternatives to antibiotics, rapid diagnostics, and vaccines

for both humans and animals.

Our approach is that we created three working groups to address incentives in each of these

areas; vaccines, diagnostics, therapeutics and anti-infective.

For a one health approach to the task, the working groups are composed of federal, PACCARB,

and NVAC, the National Vaccine Advisor Center members with subject matter expertise in both

human and animal domains.

The working groups hosted a series of meetings including two public meetings with subject

matter experts on various topics dedicated to this overall topic.

The fundamental approach is shown in this slide.

Working groups developed an analysis framework based on issues and recommendations that were

divided into four broad themes.

First was economics: issues that influence the return on investment to companies or food

animal producers regarding product development or use.

Second theme, research and development: issues related to discovery research and the developmental

process.

Third, regulatory: issues related to the federal regulatory processes that influence the development

or modification of a product ranging from basic research thru studies that meet approval

criteria.

Fourth, behavioral: issue related to the behavior of consumers, providers and companies relative

to product use or development.

We recognize that there is a lot of overlap between these four categories, but this seemed

like a useful division.

I think it's also, let me just, I would like to just thank the working group members who

are listed here in the three groups.

I won't read off everyone's names, but I will tell you that everyone involved put in a lot

of time and effort on this.

This is a process that has been going on for a year with lots of activity over this spring

and summer and we're indebted to everybody who served in this group, which included both

members of our panel, our federal ex-officios, as well as external subject matter experts

who gave important, intellectual contributions to the working group findings.

So, over the next minutes, Kent Kester and Tom Shryock, who have led an important component

of this work will be presenting the working groups top ten recommendations.

Then, the co-chairs of each of the three working groups will present recommendations from their

respective working group.

The council will deliberate on the report that has been circulated to the public as

well as to the council.

We'll consider various recommendations, and then the council will take a public vote on

this question.

So, I think that ends my introduction and now I want to turn over the microphone to

Dr. Kent Kester, who will begin the process.

>> Kent Kester: Thank you.

>> Martin Blaser: And, again, on behalf of Dr. King, he and I, we are very grateful to

all the work that has been done.

>> Kent Kester: Thank you.

Okay, thanks, Marty.

So, just a few opening comments, so the report itself is limited to antibiotic-resistant

bacteria.

It summarized issues with lots of corresponding recommendations that are discussed at length.

We're not going to discuss all the minute details today.

We focused on prevention, primarily around vaccines and alternatives to antibiotics.

The overarching goal through all this is the one health approach.

In fact, when you look at the document and some of slides that will follow, you'll see

alignment of colors and that's intended to sort of show the alignment between animal

health and human health.

There were 46 critical issues that were identified, with 64 recommendations.

And the executive summary, the focus, are the top ten recommendations, and we'll be

highlighting those shortly.

So, first, we'll go through the top recommendations and then we'll focus on more detail on all

the key recommendations generated by each of the work groups; vaccines, diagnostics,

and therapeutics, both human and animal health.

It's important to recognize that no document of this type is ever perfect, especially given

the wide range of participants on the various work groups.

The final product, I think, represents a substantial amount of focused effort, time, thought and

creative energy on the part of many who spent countless hours developing what will hopefully

be a consensus document.

In the end, the recommendations, whether in part or in total, are envisioned as starting

points for the government, HHS, USDA and others to see how best they can implement incentive

strategies.

To all who participated, and especially to our talented National Vaccine Program office

staff, great thanks is due.

So, with that, okay.

So, the inclusion of vaccines is an important aspect of the larger CCARB effort.

Since, normally we focus on really just the need for new antibiotics and better diagnostics.

So, we'll get to more details and the relevance of vaccines shortly.

In the executive summary, we focused on three main areas impacting on vaccines.

Number one is research and development.

And primarily, this revolves around providing additional funding for the development of

new product pipelines for vaccines that prevent viral or bacterial syndromes that drive antibiotic

use.

The second is regulatory.

Here we focus on optimizing the interactions between sponsors, regulatory agencies, such

as the FDA, and use policy committees, such as the ACIP.

And the third is behavioral.

And that focuses on incentivizing the uptake of vaccines by positively influencing behavior

such as reimbursement, insure first cost, first dollar coverage of vaccines.

So, in diagnostics, and you'll see some recurrent themes here, on the research and development

portion, there's emphasis on including the development of concomitant antibiotic susceptibility

testing or devices as part of any new antibiotic funding or funding strategy.

From an economic standpoint, owing to the high costs of development and regulatory approval

required for diagnostics, the idea of providing additional or enhanced financial support for

diagnostic manufacturers is important to help bring new tests to market.

And from a regulatory standpoint, in order to stream line and/or to standardize certain

aspects of antimicrobial susceptibility test development and to reduce the overall regulatory

burden.

The idea of continued funding for clinical trials, networks with common rules for shared

ROBs to reduce duplication of effort and to streamline development was felt to be very

important.

And therapeutics, the major emphasis here is to develop new economic models, so called

pull incentives, for therapies to support the currently available push incentives.

And with that, I'll give it over to Tom.

>> Thomas Shryock: All right, thank you for the relay Kent.

And we'll cover the animal health a little bit differently.

As you'll see on the graphic here, we have a black box around all three of our working

group recommendations because we have proposed, as in this overarching recommendation, two

things to be done.

The first is to develop a national policy on innovation for food-animal disease interventions,

and secondly, to fund an innovation institute housed within the umbrella of the USDA.

So, let me tell you a little more about how we came to this and why all three working

groups, within the animal sector, really feel that this is the way to go and so that's why

it's a little bit different than what our colleagues on the other side of the graphic

here have done.

So, we took, as the animal sector, a holistic approach to putting these incentives for new

product development and application, keeping in mind the objective is to improve antibiotic

stewardship in food animals and minimizing and containing antibiotic resistant bacteria.

So, we found that, as we were talking and implementing some of our initial concepts

via the fact finding or some of the pre-meeting information that we were obtaining, that prevention

of disease was highly valuable.

It was like the initial goal.

But when disease outbreaks occurred, there was a need for rapid and accurate diagnostics,

and affordable diagnostics that could guide a clinician to use the appropriate therapies,

these would be antibiotic therapies primarily, but not exclusively, and then follow that

up with some sort of an after-action review.

So, taking those in mind through the vaccines, through the diagnostics, and through the alternatives

groups was how we choose to come up with the idea that that this is the way to go.

Let's bundle these together, because they are so interlinked.

So, basically what we have decided not to include in this recommendation is the pathways

for new veterinary use antibiotics really didn't require incentives.

There's already sufficient development pathways, as well as regulatory approval pathways in

place for those companies that chose to peruse that as their candidate in future product.

So, basically, what we wanted to do was to put together this USDA-housed innovation institute,

which would be guided by the national policy, so that it could serve as an accelerator,

a springboard, a clearing house, whatever you wish to consider it to be.

So, that we could really emphasize the business of science and connect those early startup

companies, those early researchers, those folks that really need to have speed to get

their candidates into the marketplace, but have technical, as well as logistic and funding

challenges, in terms of finding information, contract research, organizations, and others.

So, we felt that this was a good way to start the process of exhibiting the basic research,

as well as applied research that needs to be done, to bring the various candidates to

the market as quickly as possible.

So, we wanted to propose that the innovation institute could serve as a connector between

existing programs within USDA, FDA, CVM and many, many other agencies who have spoken

today and have a role in product development.

So, by connecting the partners that do the research via this innovation institute can

only serve to really speed the business processes.

So, that was how we wanted to propose the funding of the innovation institute and to

be guided by the national policy.

So, real briefly then, with the idea that we had the three working groups, we have listed

in each one of those boxed here, a separate -- which one is this for?

This one?

>> Kent Kester: The one on the right.

>> Thomas Shryock: My technical consultant here.

There we go.

The three featured recommendations for each of the three working groups.

So, these will be discussed obviously in more detail.

These are just featured highlights that just tease you a little bit as to what's coming

up.

So, for vaccines, not only do we need funding, just like the counterpart on the left-hand

side here on the human side, but one example could be to support basic research in terms

of the immune systems across a species to improve the vaccine take, the immune system

responses.

For the diagnostics, educational programs on how basically veterinarians can most appropriately

use and then make decisions on the interpretations of those diagnostic tests to guide their disease

interventions.

And then, the last one here, which we'll cover later, is on anti-infectives or alternatives,

which we'll talk about later.

And providing resources basically at this point to conduct, evaluate, and create a database

of studies on these, to really firm up the effectiveness and share that information so

that appropriate choices can be made for the users of those products.

So, that's a quick overview from the animal health sector on our overarching recommendations.

And Kent, I think I'll turn it back to you.

>> Kent Kester: Okay.

Thanks Tom.

So, we'll start out with vaccines.

As I mentioned before often times in the public dialogue, vaccines are often not considered

as one of the key elements associated with combating antimicrobial resistance.

But whether one considers a vaccine that prevents infection with an antibiotic resistant or

AMR prone pathogen, or a vaccine that prevents a viral or bacterial syndrome, there's often

associated with inappropriate or overprescribing of antibiotics it's clear that vaccines have

an important role in the larger campaign against antimicrobial resistance.

So, I just -- as Dr. Blaser mentioned at the outset, I do want to acknowledge the participation,

really the subtenant participation of members from the National Vaccine Advisory Committee

on our work group.

Kim Thompson, Tim Cooke, David Fleming, Ann Ginsberg-Sodomor [spelled phonetically], and

Nate Smith.

I think their expertise and perspective was very much appreciated by all and I think added

significantly to our report.

So, for each of the areas, and this was, we read out at the last PACCARB meeting various

key issue statements and I think what we'll do today is summarize those issue statements

and then cut to the chase to the various recommendations.

So, on this one, again, we're on vaccines.

This is economic.

And the first issue statement had to do with federal and nonfederal stakeholders lacking

a common understanding about current potential economic value and societal impact of vaccines

that can reduce AMR.

Clearly, there's value in focusing on modeling and epidemiology efforts to demonstrate the

full range of health and economic benefits of vaccines with respect to AMR.

A comprehensive, multi-sectoral analysis conserved to incentivize further vaccine development.

And so, the recommendation is, logically follows, is analysis on the cost of and societal impacts

associated with new vaccine development, administration and the AMR arena develop via multiagency

process that involves our colleagues from CDC, CMS, treasury and perhaps others in the

interagency sphere, in partnership with industry and public health stakeholders.

The second issue statement on the economic side is for vaccines, is that there's limited

funding for developing infectious disease vaccines, in particular for those targeting

AMR related pathogens.

One of the challenges in vaccine development is the associated high cost and protracted

timelines.

Well, there's no shortage of scientific approaches for novel vaccines.

Smaller companies and research organizations are at a distinct disadvantage to take their

promising vaccine concepts to the full development lifecycle.

This contributes, ultimately, to the erosion in the pipeline for new vaccines that can

help address the AMR challenge.

And so, the recommendation here is an expanded range of incentives to encourage development

of vaccines that could reduce AMR by preventing the syndromes caused by bacteria and viruses

that lead to inappropriate or over-antibiotic use.

On the research and development side, the first issue statement has to do with insufficient

epidemiologic data on antibiotic use for infections caused by pathogens currently or potentially

preventable through vaccination.

Well, we recognize there're many cases of potentially vaccine preventable syndromes

for which antibiotics are inappropriately prescribed.

Our knowledge base for the scope of the problem is incomplete.

Thus, we recommend expanded surveillance by the CDC and CMS to measure antibiotic use

due to infections that could be prevented or reduced by vaccination to assess the impact

or potential impact of prevention through immunization either by existing or to be developed

vaccines.

The second issue statement, the clinical stage pipeline for vaccines targeted specifically

against bacterial pathogens associated with AMR is weak.

Focusing specifically on AMR related pathogens, something that we already heard earlier today,

that's area of interest to our colleagues at the NIH, it is clear that the overall pipeline

related to this is not robust.

And this is likely related to a combination of difficult, hard science and limited funding.

As previously, this lack of funding serves as a disincentive for developers to embark

on a challenging scientific and regulatory pathway associated with these novel vaccines.

This leads to the second recommendation, which are focus financial incentives to encourage

development of vaccines directed at pathogens that have high rates of AMR across the R&D

continuum.

This is from early to advanced development.

From a regulatory perspective, the first issue was that there still is a lack of clarity,

to a degree, about the regulatory pathways for vaccines focused on AMR and this reduces

the willingness of sponsors to develop these vaccines.

While the regulatory process associated with typical population focused vaccines, and that

I would include influenza, various pediatric combination vaccines, is very clear, the regulatory

process associated with the development of vaccines that have an AMR focus -- especially

if these are aimed at much smaller populations -- is less clear.

And to this end, we recommend early interaction between sponsors and the FDA workshops hosted

by CBER, explaining pathways and best practices, which we recognize are developing and undergoing

change as data comes in.

The second issue statement is that potential market for new vaccine, as opposed to other

AMR products, is uncertain.

Because vaccine uptake is heavily influenced by recommendations of the Advisory Committee

on Immunization Practices or ACIP.

And this impacts on funding in many cases.

Unlike drugs, there's a requirement for vaccine use recommendations to pass through the CDC

and the ACIP, following licensure approval by the FDA.

While the process and its independence are very important, early discussion of a novel

vaccine's target product profile or TPP, with both the FDA and ACIP particularly focused

on the role against AMR pathogens is important.

And thus, we recommend early communication between the manufacturer sponsors, the FDA

and CDC, to present and discuss target product profile with particular reference to impact

on AMR pathogens.

And again, this is not preordaining approval or anything like this.

This is to provide more understanding of how vaccines will be view ultimately as they progress

through the developmental and regulatory lifecycle.

From a behavioral standpoint, the first issue statement involves implementation strategies

for optimal vaccine acceptance and utilization are inadequate.

As we discussed yesterday in our session on antimicrobial stewardship, the need for culture

change in the area of, with respect to vaccines and their role in combating AMR is important.

Implementation research is an important aspect of this.

Also, approaches to increased positive reimbursement coverage for all vaccines would similarly

appear to be an important incentive for expanded vaccine uptake.

Thus, programs and interventions based on behavioral insights that aim to increase vaccine

uptake are recommended and continued broadened economic incentives to influence behavior

and increase uptake such as reimbursement to ensure first dollar coverage; that is,

insurance coverage of vaccines without copayments or coinsurance costs for all ages, not just

children.

And finally, the second issue statement, providers lack knowledge about the role of vaccines

in preventing AMR.

As with antibiotic prescribing, a focused educational campaign dealing with vaccines

would also be an important incentive and could be something that testing could assess over

time.

Thus, focused governmental, vaccine-centric, educational policies and approaches, including

vaccination as a means of achieving antibiotic stewardship with involvement of healthcare

facilities, health-related educational institutions such as medical schools and academic health

centers would be similarly important.

And with that, I'll turn it over to Angie.

You want me to or --

>> Angela Caliendo: Okay, thanks.

So, you know, we had considerable discussion on diagnostics yesterday and this morning

and many of the issues that were brought up are going to be addressed in our recommendations.

So, I'm going to start with the economic recommendations first and the first issue statement here for

us is following approval of new antibiotics corresponding ASTs are not immediately available

to insure proper use of the antibiotic.

So, if the laboratory can't test for the antibiotic, there's a disincentive for clinicians to use

it.

And so, our recommendation here is funding for the development of new antibiotics should

always include the development of a concomitant AST device and, you heard Dr. Bitterman talk

about this.

This is a process that's well underway now and at the FDA.

And just for clarification, what we're referring to here are simple devices, maybe an E-test,

maybe a disc.

Not necessarily that every automated system is expected to be up and running at the time

that the antibiotic is approved.

So, issue statement number two, because there's no method to determine really the value of

a diagnostic test, we don't have alignment of reimbursement with that value.

And so, to address this, we recommend a reimbursement plus system, particularly for test of key

public health importance and the example that we use is CRE colonization testing.

And public health agencies such as CMS really need to help us and assist us with these sorts

of decisions.

Just so you understand, what we're trying to encourage is having reimbursement drive

the use of the best diagnostic test.

Not necessarily the cheapest or the one that's reimbursed the best, but in fact the one that's

clinically most appropriate.

Issue statement number three is, there's a lack of outcome studies and we've heard that

several times over the course of this meeting.

And so, our recommendation there is to increase the funding of diagnostic outcome studies

and there's a variety of agencies that could do that, ARC, CDC, PCORI, the NIH, the Department

of Defense.

And really, the goal is we need to assess patient outcomes, length of stay, change in

antibiotic use, rates of antibiotic use in certain populations and the cost of care.

Issue statement number four is the high cost of development of diagnostics is a disincentive

for diagnostic companies.

And so, our recommendation here is to focus on a tax credit for a portion of the qualified

clinical testing expense.

This is where a lot of the expense for the companies lies, is running clinical trials,

and if there was a way to have a tax credit, we thought possibly modeled after the orphan

drug tax credit.

Okay, so let's move to the R&D recommendations.

We have identified several unmet needs in the diagnostic arena.

One of them is a rapid point of care test that could be used in the outpatient setting

to distinguish bacterial from viral infections.

Another is on the inpatient side, is there a better biomarker that we could use to help

us determine when to start antibiotics and maybe more importantly when to stop antibiotics?

And then, third, is tests that detect bacteria directly from the clinical specimen.

So, skipping the entire step of culture and going directly into blood or directly into

a sterile site to identify bacteria and also to have rapid susceptibility results.

And so, the recommendations to address these unmet needs, one is to sustain investment

in funding mechanisms for developing new, cost-effective diagnostic test and updating

existing diagnostic tests through the small business innovation research and small business

technology transfer grants.

These have been very successful mechanisms to date for particularly smaller companies

and we have multiple diagnostics that are on the market now that came through this mechanism

of funding.

The other recommendation is to expand funding of a clinical trials network and the example

here is the NIH supported ARLG and to insure that the networks work though a common IRB.

The cost of the clinical trials, the logistics of the clinical trials are a big challenge

for the diagnostic companies and the purpose of this recommendation is to simplify that

process for the companies.

Issue statement four is collaboration between diagnostic companies and other stakeholders

is limited and inconsistent, and can sometimes lead to the company not having a good understanding

of the best test to develop.

And so, we thought it would be helpful for the federal government agencies to get together,

and you see them all listed here, and create a list of the most critically needed diagnostics

for combating AMR so that when companies are interested in getting involved in this area,

they have an understanding of where the needs are and they can direct their investment accordingly.

Okay, let's move on to regulatory recommendations.

So, the first statement here is the regulatory approval process for clearance of devices

for modifying and improving existing devices is complex and expensive.

So, here we have a test that's already approved and we want to expand to another clinic use,

or what if you have a respiratory test and there's a new influenza virus and you want

to add that to your test?

How can we simplify that process?

And so, we recommend advancing the FDA regulatory efforts that are currently ongoing for improvements

or updates of existing tests that utilize post-marketing study results and real-world

evidence to promote the development of improved tests.

And so, instead of needing to present all of the data to the FDA prior to approval,

some of that data could be collected once it's in clinical use.

And, as I said, this again is something that the FDA is in the process of implementing

and we think it will be very helpful for companies.

Issue statement number two in this area is the same general concept.

Current regulatory process for new tests, so tests that haven't been approved yet, is

time-consuming and costly and poses a disincentive for test developers.

And so, our additional recommendations here, again, are to enhance the clinical trial network

that, and the key really is functioning with a common IRB because that simplifies the logistics

for the company considerably.

And also for the laboratories that may be participating.

Second is to modify the requirements to simplify the process for obtaining CLIA waivers.

CLIA waiver is the status that's necessary so that a test can be performed out of a clinical

lab, by non-laboratory professionals.

So, you can have a nurse or an MA right in the office, right in the emergency room perform

the test.

And so, that regulatory process has gotten a little more complicated over recent years

and is there a way to simplify that?

An additional recommendation again is to utilize post marketing study results in real world

evidence to facilitate the approval of a new diagnostic.

And then, the complementary structuring of the FDA, CDC, Antimicrobial Resistant Isolate

Bank and the ARLG Virtual Biorepository to increase access for diagnostic companies.

And we hear a lot about that this morning, that these repositories are used by companies

quite extensively and is there a way to facilitate that process more effectively.

And finally, the last issue in the regulatory arena is hospitals are currently not required

to update their microbiology lab.

So, if there's new technologies that are out there, there is no requirement that a laboratory

needs to adopt them; particularly, ones that are proven to, you know, improve outcome or

get an answer to the clinician more rapidly.

And so, our recommendation here is that CLIA requirements that update microbiology laboratories

technologies become a part of the accreditation process.

We already have a very well-established accreditation process for laboratories.

We'd just like to add this to it.

And finally, under behavioral recommendations, as we learned a lot yesterday, clinicians

don't always use diagnostic tests, they don't believe the results, they don't act on them

once the results are available, and so we had several recommendations here.

The first is really evidence-based research that's supported by public and private resources

to actually help us develop a better understanding of the behavior that affects these decisions.

Why aren't diagnostics used?

We don't really understand what's behind this and really the goal is to identify drivers

that prevent adoption.

And also, this is something that is ongoing and is the inclusion of experts in clinical

use of diagnostics onto clinical guideline committees.

And so, that they can bring their expertise and perspective on diagnostics into the guidelines.

Third is clinician education on the use and interoperation of diagnostic tests.

And finally, the development of tools and mechanisms that improve a clinician's ability

to make decisions in the ambulatory setting.

And one of the things that we talked about in our working group was, you know, envision

everybody connected into an EMR so that the doc sees the patient, puts in an order, orders

a test, the test result is done, sent to the pharmacy, and the pharmacy doesn't even release

the antibiotic unless the test is appropriate.

It's either positive for flu, they would release an antiviral, if it's not, they would not.

And, you know, with all the EMR efforts out there, can we start integrating them in ways

that actually help clinicians.

So, that was the extent of what we had on the diagnostic side.

I'm going to turn things over to Dr. John Rex, who will talk about incentives for therapeutics.

>> John Rex: Thank you.

Next slide please.

Actually that's me, I did that.

[laughter]

It was happening by magic -- I was watching Angie there, and she said and it happened.

[laughter]

Here we go.

So, again, across the four categories, the first one is the economics, and you'll have

noted that our one topline recommendation out of the therapeutics group is for an economic

attack on the problem.

And the fundamental, underlying issue statement is that the return on investment for developing

new antibiotics is unpredictable because of antibiotic resistance and related restrictions

on use of new agents.

And this is a recurring issue that is actually going to go to all four of them and it's the

reason why the one recommendation of this group focuses on this topic.

There's been a huge amount of work in this area to be leveraged, drive AB, the work of

the Duke-Margolis Group and a way to summarize it is the four bullet points on this slide.

The first is something that Joe Larsen said, loudly, that you need a combination of general

and targeted incentives to introduce a more predictable ORI including push and pull.

You can't just do part of it, it's a balanced ecosystem.

So, on the push side, we need to continue to do what we're doing by providing push incentives

across all phases of discovery and development.

We're doing this.

There's a significant amount of money going into it; could be increased, but there's definitely

money going in.

We must, must, must adopt some form of a de-linkage model as a pull incentive.

There are a number of models for this now floating around and we feel like CMS and the

treasury need to think seriously about this and to think about value metrics for antibiotics

and diagnostics.

The required size of a de-linked market entry ward, options for plausible models including

de-linkage and to do this in consultation with FDA, CEC, public health experts and the

international community.

I'd say this conversation is happening globally, there's a lot to be tapped into here and there's

clearly, the tools exist.

What we know need to do is actually do it.

On R&D, there are a pair of issue statements that work together.

The first is that while it's easy to kill bacteria with steam and fire and bleach, killing

bacteria without also harming the patient is difficult.

And the second is that a paradox about antibiotic development, which is that we'd like to have

studies showing the utility of a new antibiotic against resistive bacteria, but that means

that you've actually got to have people who are infected with the resistant bacteria,

which is not a happy place to be.

So, we're actually quite constrained in the nature of the clinical trials that we can

do routinely, particularly as we invent one or two new drugs, it makes it harder and harder.

And actually it's also good for the patient.

It's good that's it's hard to do this.

To be able to do these studies so, the things that we need to do to bring this together,

shown on this slide.

We need to strengthen the funding for existing mechanisms for innovation R&D picking up from

the previous slide.

FDA needs to continue its excellent work on thinking about refined guidance documents

with a particular emphasis on expanding the guidance on narrow spectrum agents for unmedical

need.

This has been a real focus of the last years' worth of work and I want to complement them

on that.

We just have more to do.

And finally, we need to think about ways to make clinical trials more efficient and less

costly and clinical trial networks based on common master protocols facilitated by BARDA

and NIH could accelerate phase two and phase three programs.

For agents that have adequate spectrum to treat an entire syndrome and that's a topic

that you're going to see appearing over the next year or so.

Regulatory front, there are two issues here, and I've kind of already said them.

Issue statement number one in the document is read out, it's difficult for manufacturers

to develop clear and specific data for any new drug efficiency and infections caused

by highly resistant bacteria.

Let me emphasize again that that's a good thing that it's hard to do that because when

that's easy to do, somebody's dying.

We want that to be hard to do.

The other issue statement is that it's hard to enroll the number of patients needed to

show efficiency of a narrow spectrum antibiotic because of the low rate of infections caused

by specific pathogens.

There are few narrow spectrum cases like staph aureus and gonorrhea where it's not that hard.

But the ones that we really care, the gram negative bacteria, it is quite difficult to

do this.

And again, it's a good thing, but we also want those drugs.

So, the corresponding recommendations are, first is one that has to do with changing

the way we think about this problem.

Via its regular [unintelligible] interactions, the FDA is changing the normative view on

what is an acceptable program.

We've now all clearly stated in public that an acceptable program for a new drug, well

we just saw one get approved, the Vabomere approval, which is a UTI study and an open

label study against some resistant pathogens.

And that's normative.

That's all we're going to get in the future.

We've got to live with that.

And then, CMS treasury under the relevant US government agencies need to look at that

set of data and say, well that's all I'm actually going to have, and that's how I have to think

about this going forward.

And here I point it work by Ramanan, where you're going to see some papers on HTA approaches

beginning to appear in the literature that come out of drive AB.

Talking about all the stuff we can leverage in the universe.

Finally, last slide, behavioral.

The issue statement here is this is not a negative one.

Stewardship activities are appropriately limit the use of current and new antibiotics.

Therefore, novel antibiotics have a low financial ROI from the perspective of the developers.

I'm actually ending where I started.

And the action here is the continued efforts by CMS and treasury, and actually the entire

community to insure that solutions to this problem incorporate incentives and simultaneously

support stewardship.

And I should also say, I left off access on that slide.

So, those are the things that need to be brought together to make the entire ecosystem work.

Thanks.

And next, it's over to Randy Singer.

>> Randall Singer: Okay, great.

We're going to shift now over to the animal health side and I'm just going to start generally

by acknowledging that the ways in which we're using antibiotics in animal agriculture.

It's changing rapidly.

It's changing dramatically.

That's both within the US and globally.

There is a consorted effort, a focus on stewardship, on appropriate antibiotic use in animal agriculture

and this entails then that we emphasize how we're going to replace some of these antibiotic

uses that have been in place for many years with other approaches for maintaining animal

health and how we're going to use the antibiotics that we do have as appropriately and responsibly

as possible.

And as we talk about the shift that we'll seeing and how we maintain animal health,

we need to be cognizant of the fact that the entire cost of these interventions that we'll

be discussing are typically born by the producer.

They're -- this is why we really are talking incentives in a different way than on the

human health side.

How do we get some of these interventions utilized when they represent an actual cost

to the end user?

So, I'll start then, for my section on the incentives for vaccines, and I want to acknowledge

the hard work of Liz Wagstrom, Cyril Gay, and Brian McCluskey, who really did a lot

of the heavy lifting in this section.

In animal health, vaccines have been used for decades, many decades, as a cornerstone

of disease prevention.

As we discuss their relevance with antibiotic use and resistance, it's important to remember

that the challenge we have in animal agriculture is that we're not just trying to control pathogens

that cause disease to animals, but also pathogens that may be transmitted through the food chain

and impact human health.

They may have absolutely no relevance to animal health.

So, we have this duality in the kinds of pathogens we're trying to prevent.

When we talk about the ways in which we use antibiotics, we are trying to either reduce

the bacteria; infections that would result in the use of an antibiotic, but we're also

talking about trying to eliminate the viral infections that might, in animal systems result

in a secondary bacterial infection that then require the antibiotic.

So, it's not just that viral infections are being treated inappropriately, it's that in

animal agriculture many of the viral infections result in secondary bacterial infections.

Again, we're also trying to reduce pathogens.

You can take a salmonella, a campel abactor [spelled phonetically] presence on a farm,

rarely causing any disease in the animal population, but we're trying to reduce those, as well.

So, within the economic piece, we really had one major issue statement, and it comes down

to the notion that for many antibiotics, the cost of purchasing and administering vaccines

can outweigh the cost of purchasing and administering antibiotics.

And so, there is a major incentive here.

There has to be a way to reduce the costs of these vaccines that reduce both bacterial

and viral disease impact on animal populations, so that we can reduce the need for antibiotics.

There has to be a way to make the use of these vaccines cost effective.

When we talk return on investment, we're often talking about how it impacts that producer.

Within research and development, we have three major issue statements.

The first is related to the limited funding that is available for some of the basic research

we still need on the immune systems of some of our key animal species.

Remember, we are dealing with many animal species, not just one, and their immune systems

are highly variable across species.

So, some of the research that is needed to be able to develop next generation vaccines,

adjuvants, and the administration tools is in desperate need of funding.

So, our two recommendations.

First, that we need funding to support the basic research of immune systems across these

species and I know, again, we are asking for money.

We need incentives that is related to funding and I think what we've heard throughout this

meeting and past PACCARB meetings, is that on the animal health side, the agencies are

severely underfunded for this one health issue.

And this aspect of the basics of the immune system is another key aspect of being able

to develop an intervention to reduce the need for antibiotics.

Related to that is sufficient funding for, as Dr. Shryock commented, the innovation institute,

which again would house many of the activities that we're discussing including a way to incorporate

vaccines into an overall health management program.

A second issue statement is related to the vaccine delivery systems for mass vaccination.

Many of these are not optimized for some of the specific animal pathogen production scenarios.

Some of the vaccines that we use injectable and that could be also into the egg, not just

into the animal, but we have many vaccines as well that are aerosolized so a spray vaccine,

they may be water, they use a water system for distribution and the ways in which many

of these pathogen delivery systems are developed aren't necessarily optimized.

We do need research in that area, so we're asking again for funding provided through

this innovation institute that is dedicated to supporting improved vaccine delivery in

animal production.

We are hoping that this would be a shared funding across agencies.

We talk one health, we really need to see the government agencies work together that

includes an emphasis on the animal side given that the end is a benefit to the human health

sector.

A third issue statement relates to something that Dr. Kester already mentioned, which is

the epidemiologic data are currently insufficient about the use of antibiotics for infections

caused by pathogens that are currently or potentially preventable through vaccination.

We desperately need studies that can estimate how much antibiotic use could be eliminated

through the use of vaccines, including the use of viral vaccines.

This includes field studies, it includes models, but it needs to be able to demonstrate the

effectiveness of these vaccines, a benefit to animal health, a return on investment for

the end user, and then, quantify how much antibiotic might we be able to eliminate out

of that production system.

On the regulatory front, there is a single-issue statement and it relates to that the processes,

the regulatory processes prevent a flexible approach and rapid approval of vaccine strain

updates in vaccine development.

For the animal agricultural sector, the vaccines are approved through the USDA's Center for

Veterinary Biologics and there are some hurdles when you want to change out the strains that

are incorporated into the vaccines.

So, we, through our recommendation, want to see a process evaluation by the USDA Center

for Veterinary Biologics to improve the speed of approval of these new strains into the

commercial vaccines.

And finally, the single-issue statement for the behavioral component, this is so critical.

It's really challenging for the producers and for the veterinarians to integrate new

vaccines and new vaccine strategies into their overall health management programs, while

balancing productivity, animal welfare and that return on investment.

So, we need education.

We need training on how do we assess the effectiveness of this disease prevention programs that balance

these various components including welfare through improvements in veterinary and animal

science curricula, continuing education, funding for training programs; again, all about how

do we adopt these vaccines, make it affordable for the end user, the producer, while maintaining

the productivity and welfare of their animal system.

And with that, I'll pass it to Dr. Davies for diagnostics.

>> Peter Davies: Thanks Randy.

And I'd just like to thank all the members of the working group who helped us out on

this issue.

First of all, just generally, a lot of the issues that were, Angie discussed on the human

side reflected pretty much equally or even more so on the animal side.

Just to outline the scope of the activities we had here, certainly we recognize the role

of the companion animal sector with respect to contribution to the AMR picture, but the

scope of the working group here was focused very much on the food animal populations rather

than companion animal populations.

Just to put the diagnostic situation in perspective, on the food animal scenarios, diagnoses overridingly

a population activity.

So, we're looking at outbreaks of diseases in population.

Certainly individual animal diagnosis and treatment is an important part of it, but

particularly in the larger and intensive populations, therapeutic decision making is often based

on both diagnostics conducted on samples of populations and on therapeutic decisions that

might be applied to populations.

So, we have a very different context for applying diagnostics.

Just to move onto our first issue statement, and again, this reflects on the human side

a dearth of clinical outcomes studies, I think in all aspects of therapeutic decision making

and antibiotic treatment.

Sorry.

And particularly, well, including the use of diagnostics.

So, our first recommendation here, well the issue statement [unintelligible], is that

we need show that the use of diagnostic tests can prevent or particularly or quickly protect

the emergence of antibiotic resistant bacteria and it's cost effective.

And the recommendation, as you can see there on side of that, is through the innovation

institute that's being proposed both funding, and perhaps even as importantly potentially

coordination of clinical outcome studies that include a fairly broad spectrum of animal

health and welfare outcomes, resistance emergence, and importantly, impact on cost of production,

because technologies tend to be taken up very quickly in the animal industries with financial

benefits demonstrable.

And it's important that all aspects of the economic impact of proposed approaches is

taken into account.

And I think within each of the food animal industries, obviously there's a need for prioritization

to really be able to decide which of particular disease issues that are, could most beneficially

be addressed by clinical outcome studies.

Because in all species, really, a lot of therapeutic decisions are associated with a relatively

small number of relatively well characterized disease conditions.

The second issue statement we have is, arrived at, that the use of diagnostic testing could

be limited by the expense that is incurred.

I think we should point out here that in the U.S., we have a -- we are very privileged

to have a very high level of veterinary diagnostic infrastructure, largely through our state

veterinary diagnostic laboratories and also the federal laboratories that coordinate and

support them.

The other point on cost of testing is particularly in the context of population testing.

The cost of the individual test is not necessarily that high in relation to the cost of the therapeutic

decision that's being made, which could be involving large costs of animal health negative

outcomes.

So, that balance is a little bit different than at a population level, the individual

test cost is perhaps not as important as in other settings.

So, our recommendation with respect this issue statement is, really, the need to insure ongoing

financial support for the veterinary diagnostic infrastructure that we have in the country

that performs all of the animal diagnostic testing, but also, specifically including

susceptibility testing for animal pathogens.

Okay, moving on to our R&D recommendations, and here I think we, the duality that Randy

spoke of with respect to issues in animal health and issues for potential human health

link to food animal populations and the food supply system is very clear because we couldn't

be focusing diagnostics on priority animal pathogens, but we know that in most cases

the importance on our particularly foodborne pathogens are often occurring in those populations

when they're very health animals with no disease associated with it.

So, we need to look at both sides of the picture there.

Our first issue statement again, reflecting the situation in human medicine is that there's

very few tests that rapidly identify pathogens or provide reputable susceptibility tests

in food animal medicines.

Our recommendation here, again, is investment in research on diagnostics that can rapidly

identify pathogens in food animals and provide rapid susceptibility results directly from

the clinical specimens in the field setting, understanding that in many cases these decisions

are made not in very remote situations.

So, it's not just, really, waiting for diagnostic processing time in a laboratory, but you have

sample transport delays that can be considerable in some areas.

The context of what is rapid then can be very variable for animals where you are making

immediate therapeutic decision in a remote situation to sometimes -- which could be quite

longer in some population settings if the decision is really related to a population

level treatment.

So, what is sufficiently rapid in the veterinary setting is, I think, highly variable depending

on the context that people are facing.

Randy mentioned before the sort of imbalance between the resources available on the human

and animal side, and I think that this is an area where in looking at rapid testing

and new technologies, for diagnostics that we might expect that there'd be more rapid

progress on the human side, and so our recommendation here is to be aware and looking for investment

in translational research that able to adopt new technological platforms and diagnostics

developed for humans into the animal setting because it's likely that they will be highly

transferable and that we're looking at generally bacteria that are closely related, often.

So, there's a lot of potential perhaps for technology transfer from the human to the

animal sector.

The next issue statement relates more specifically to the foodborne disease scenario and the

issue statement here is novel diagnostics are needed to advance process control in the

harvest and post-harvest sectors.

Here, meaning the post-farm sectors of the food supply chain, to reduce exposure risk

to the human population.

So, one of the successes, I think, that we've had regulatory wise over the last 20 years

or so, is that we've had a measurable reduction in the incidents of foodborne diseases for

most of our major bacterial pathogens that are associated at least with terrestrial animals

and a lot of that has been driven by greater focus on carcass hygiene and introduction

of microbiological standards for carcasses.

That happened in 1996 with federal regulation.

We're still using that at a culture-based method, so I think in line with new opportunities

here, we're recommending that there should be support for research to develop culture

independent methods of detecting microbial contamination of carcasses and meats as a

tool for improved process control.

And I think it's keen to point out here, that testing on an individual carcass in animal

disposition approach is probably never going to be economically feasible.

But we could apply the diagnostics to improve processes and under processes at a better

throughout the food supply chain.

The third issue statement we have here is additional information needed on antimicrobial

susceptible testing for key animal pathogens, including validated, clinical breakpoints.

So, we do have a process that's been going on for many years through CLSI to establish

breakpoints for testing of animal pathogens, but it's an incomplete process.

So, we still have, through lack of research investment in many cases, many important animal

pathogens where we either do not have breakpoints that have been established or in other cases

the human breakpoints for the same or related pathogens are just translated into the veterinary

sector.

So, here, we're recommending that research grants for generation and integration of additional

data that's necessary for that process to progress to establish test methods, quality

control range data, all the things they do for a priority animal pathogens for which

there's currently no breakpoints available or for where human breakpoints will do.

So, obviously the value of the antimicrobial susceptibility testing would promote people

to do is dependent on the reliability to translate those breakpoints into a clinical setting.

Moving on to the regulatory recommendations, we can be brief here.

Even though both FDA and USDA have some oversight of animal diagnostic tests, it's largely related

to labeling safety and they're adequately represented.

And the market for veterinary diagnostics is essentially a market-driven one.

As I mentioned before, successful technology tends to be adopted fairly quickly, so the

market is alive there.

So, we don't see any regulatory issues that are probably impacting the development of

diagnostic tests.

The final consideration is the behavioral recommendations, and we had some wonderful

material yesterday related to behavior and therapeutic decision making and prescribing.

I think this is an area again, where we can say that's fairly new on the human medicine

side and it is novel on the animal side.

So, I think our issue statement written is that there's negligible evidence based data

about how veterinarians incorporate diagnostic testing's into making decisions to employ

antibiotic therapy and I think we can extend that further, just to the whole practice of

prescribing.

So, here we're recommending support for research into therapeutic decision-making behavior

in veterinary medicine, including the use of susceptibility testing and potential for

rapid diagnostics.

And secondly, again, and similar to the human recommendations, opportunities for better

educational programs for veterinarians on use and interpretation of diagnostic tests,

stronger curricula and continuing education programs linked to antibiotic stewardship.

Thank you.

And with that, I'll pass back to Tom.

>> Thomas Shryock: All right, we're in the homestretch here.

This is the incentives for alternatives.

You noticed earlier on that we had used the word anti-infectives, now we're changing it

a little bit and calling it alternatives.

And so, I'd like to define, really quickly, what we mean by the word for this particular

presentation.

And here we're talking about non-antibiotic disease interventions.

They're administered to food animals regardless of whether intended for disease prevention

control or treatment.

They're not necessarily interchangeable with or substitutes for antibiotic products.

So, keep that in mind as we go through the next few slides here.

So, our economic considerations in issue one, basically is very similar to what Joe Larsen

was talking about from BARDA.

Funding is lacking to generate a sufficient pool, high quality alternative candidates

in the early and middle stages of R&D.

So, our three recommendations, along the line here to address this would be not only to

fund the innovation institute to get things going, but to basically look at maybe some

user fees to supplement or replace agency funding that might be initially used to get

that off the ground.

The second recommendation here is to use that innovation institute as yet another tool to

encourage CBER funding, which was mentioned by Angie and others, and private sector investment

activities.

Getting the support of that institute for additional, extra funding to advance these

early stage candidates to the point where then in number three recommendation here,

the technology transfer pathways can be facilitated from those early to mid-stage candidates for

acquisition by companies that have a little more breath in interest and ability to carry

them across the regulatory and developmental pipelines and into the marketplace.

Our R&D recommendations, here we have two issue statements.

The first one that we'll talk about here is that small companies, government agencies,

independent investors that don't really have available resources, and mostly in terms of

personnel, to conduct the key activities that are needed to de-risk the alternatives as

they move from the early stages toward the middle stages.

So, things like proof of concept, early safety studies, even some manufacturing studies,

for example.

So, the recommendation here would be that the innovation institute can provide support

services really in the way of connecting the innovators across the sectors to get those

services that they need to advance their candidates in the R&D sector.

And then, aligned with that is that the specific solutions that could be outlined in the national

policies to be developed, really can be used to include what kind of contract research

organizations?

What kind of connectivity might the innovation institute have to blend the resources to the

needs, the needs to the resources to get those early stage candidates moved along?

And then, our second issue statement here has to do a little bit more with the idea

that having information on the effectiveness and the efficacy of these alternative products

could be combined with data that's collected in an actual field production setting so that

you can begin to compare what is actually happening across different farm sectors.

So, to expedite that, the R&D recommendation here would be either outright grants or connectivity

to funding sources to actually get that work done with a caveat that the data generated

would be entered into a larger data pool for larger evaluation, maybe a big data type of

evaluation.

So, the innovation institute could help with advancing RFPs, for which proposals could

be submitted and the funding obtained, or just outright grant funding.

Our regulatory considerations then would be two-fold with issue statements.

The first would be, lots of times the early stage developers, just two, three, four, five

people in a company, don't really know who to turn to, whether it's USDA, it's CVM, it's

somewhere else, perhaps maybe even EPA.

So, how do you get to the right people in the right way in the shortest amount of time?

So, one of the points of contact could be through the innovation institute.

So, thinking of it as a clearing house or a one-stop shop could provide that connectivity.

So, this could supplement, not to replace or be redundant to the existing programs,

the USDA and CVM already have, but just make sure those connections and the communication

are more readily accessible for those who are basically the resource constraint to get

that information.

A second issue here is while there may be standardized guidance with antibiotics in

mind, or other vender and medicinal products, often times with these alternatives there

may be a need for flexibility in how the guidance documents could be interpreted or adapted

so that the developers could actually meet the evidentiary requirements of the regulatory

agencies.

So, the recommendation here is to really provide the resources to the regulatory authorities

to enable them to keep abreast of the latest technologies so that they can be conversant

with and even suggest alternative studies and approaches and data evaluation, such that

the sponsors then can generate the data that meets those requirements for approval in a

more easy fashion rather than relying on a specific guidance that may not be quite appropriate

for the innovation at hand.

And then, our last topic here on behavioral recommendations has to do with a very early

stage of candidates.

And this would be that researchers sometimes lack the business value awareness and the

process of patenting novel technologies.

So, the recommendation here would be that maybe there's a need through the innovation

institute to bring that to light to those developers, researchers and others who maybe

just don't know, or haven't thought through the implications of the timing or other things

like that.

A second possibility would be some sort of patent application fee reimbursement or post-patent

award or something like that to encourage developers or innovators at that very early

stage so the technology is not lost for lack of coverage.

A very important point for those who wish to acquire technology transfer later on.

Our second issue statement here is related to one we talked a little bit about in the

R&D that the effectiveness of alternatives, because they lack trust in their effectiveness

and their safety.

So, having those studies done enables the behavior to be altered such that there's more

trust in the product.

There's more confidence going forward that this would be an appropriate tool to use to

prevent, control or treat a disease.

So, that really wraps up the behavioral aspects.

And it also concludes the working group recommendations in this report.

So, with that I will end and turn it back to our chairs, Marty and Lonnie

>> Martin Blaser: Thank you, co-chairs.

I think we can see that the committee has done very thorough work with much detail and

much depth.

I think it's a really remarkable body of work.

For more infomation >> PACCARB 7th Public Meeting Day 2, Pt 4: REPORT OUT: Working Group Activity - Duration: 1:10:44.

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Praise in Public and Criticize in Private - Duration: 2:29.

Hello, this is Mikel with Tiny Frog Technologies.

I want to talk a little bit about - as a business owner - I'd like to talk a little bit outside

the realm of creating websites, more about things that I've done in building my business.

I started the company in 2003 so it's been quite awhile and over the course of 13 years

now I've worked with many employees, contractors, clients, vendors, suppliers, and so forth and so on.

And when I started my business, someone had given me this kind of idea or principle to

run a business by that I have continued to use and it's been super-effective - it's called

praise in public, criticize in private.

So I really I found that having worked in companies in the past when I get praised in

public it tends to give me a really good feeling.

I found when I've been criticized in public it tends to give me a really bad feeling.

I've found when I have been criticized or someone's giving me recommendations about

how to improve in a private setting it's much easier for me to take from an ego perspective,

and much easier for me to accept.

So I really applied that principle to how I work with people in my business from every area.

Once again employees, contractors, clients, prospective clients, vendors, suppliers, so

forth and so on.

And I've found it works really well.

So if someone does something that's really good, it's easy to kind of glaze over that,

or not pay attention to it, or not acknowledge it.

But anytime I get positive feedback from a client, for example, about one of the people

that I work with - I really go out of my way to acknowledge that person and make sure that

they realize that they've been acknowledged.

Acknowledged from me and my client.

And on the other side of the fence - once again criticizing in private I found that

in pointing out areas where people need to improve in private I found that it's a much

more effective tactic than doing it in a public setting which is really demeaning and mean.

So I just want to mention that I think this is a really important principle to use when

you're working with anyone.

Thank you this is Mikel with Tiny Frog Technologies.

For more infomation >> Praise in Public and Criticize in Private - Duration: 2:29.

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PACCARB 7th Public Meeting Day 2, Pt 5: Council Discussion and Vote, Public Comments and Adjourn - Duration: 24:46.

>> Martin Blaser: Before we go on to our council discussion,

I just want to make a thanks to the staff of PACCARB, who have really enabled all this

work.

I want to thank Bruce, who served for a good half of this process before he left the federal

government.

Our -- Jomana Musmar, who has led it since Bruce, and even before.

Laura Gottschalk, MacKenzie Robertson, Tiffany Archuleta -- I well, and others.

So thank you to the staff.

Now it is time for the council to --

[applause]

And now it is time for the council to have public discussion.

Each of you has seen this report in its draft along the way.

You've seen it maybe too many times.

But now is an opportunity to speak in public about your thoughts.

Councilors.

Just so that there is some discussion, I would just like to say that I am in very high agreement

with this report, and we were very -- it was difficult to come up with the top 10, because

there were so many of value.

And I'd like to propose an eleventh.

It will not go into the report as number 11, but just for the purpose of public announcement,

and that has to do with human therapeutics, item 3.2, page 18, sections 3.2 and 3.3.

It's about the development of narrow spectrum antibiotics.

This is a little future oriented.

It's not necessarily for the current round of antibiotic resistant organisms.

But it's an attempt to lower the ecological damage of antibiotics on our microbiomes.

And I'm predicting that the future of antibiotic development will include more and more of

narrow spectrum, once we have adequate diagnostics that will enable us to find these organisms.

And so in our report, we asked for the continued development and refinement of such of these

and to improve the regulatory pathway, and to have further ways to make the development

of narrow spectrum antibiotics more feasible and bring it to the market sooner.

Dr. Laxminarayan.

>> Ramanan Laxminarayan: Thanks, Marty.

So again, I'd like to echo what you said about you know, this having been a long process

but included a lot of people who are not here today, and I think we can be quite happy with

what has emerged from the process.

Just three points.

One is, for those seeing it for the first time, you're probably wondering this looks

like a lot of money.

There's many parts which call for innovation institutes, for, you know, rewards and mechanisms

and so forth, and whether all of this will actually come to pass.

I think that the way to read this would be to sort of see perhaps that there are things

that could happen in the more immediate term, such as for instance, the clinical trials

network, which could lower the cost of drug development.

That could happen very soon.

You know, regulatory pathways that were optimized and, you know, as we've already seen, already

happening to some extent you know, at FDA.

Now these are things that could happen right away without the need for the big bucks, which

will undoubtedly be necessary.

So I don't think, you know, those seeing it for the first time should be worried as, you

know, as this being a very expensive proposition that will never see the light of day.

It does not have to be adopted in its entirety.

It can be adopted in a sequential manner, you know, with starting with the things that

are the most feasible to do.

I think the second point here to make is that I'm not, I mean, I'm aware of these processes

in other countries, and you know we've been involved in this process in the European side

as well with IMI.

This may be the first process that has actually looked at human and animal use simultaneously

anywhere in the world.

So, I think it has a lot of merit from having that cross talk as part of the discussion.

And I think it will be important for us to at this stage, not lose sight of it, and have

these split off into separate allocations.

I think it's as important to get money for vaccines for animals as it is for humans,

and I think the way in which we advocate it will be important.

And I think the third part of it is really in terms of time length, which these obviously

are things which will take a very long period of time, so hopefully our co-chairs will be

advocating for this report very strongly with the powers that be to make sure that it goes

into practice as soon as possible.

Thank you.

>> Martin Blaser: Thank you for your comments.

I'd like to call on Alicia Cole, who is on the phone.

Alisha, can you hear us?

>> Alicia Cole: Yes, I can.

Yes, I can.

Thank you.

>> Martin Blaser: The floor is yours.

>> Alicia Cole: Thank you.

I wanted to commend my fellow committee members for the report, and for all the hard work

that everyone has done.

I just had one comment on -- Angie, there was a section on point number three where

you talked about funding of diagnostic outcome studies.

And I noticed throughout some of our bullet points we call out various federal agencies,

and it's probably just an oversight, but I think we need to also include the V.A.

Especially where we talk about outcome studies, because the V.A. is the largest integrated

health system in the U.S.

They've got 1700 [unintelligible], and so where we're looking at outcomes and other

point of care studies, I think they should be included.

I think they bring a strong voice to the table.

They're having great success, and I think we need to incorporate them in a very specific

called-out way and not just implied.

So I'd like to make that recommendation.

Thank you.

>> Angela Caliendo: So just a question -- clarification, Alisha.

Are you talking about the V.A. funding these studies, or the V.A. being funded for these

studies?

>> Alicia Cole: Being funded for these studies.

>> Angela Caliendo: Okay, so the organizations that we listed

were those that would actually provide the funding.

>> Alicia Cole: Okay.

>> Martin Blaser: And so the V.A. could be a recipient, and

as you point out, is a very good, large scale way to test ideas and products.

>> Alicia Cole: Absolutely.

Thank you for the clarification.

>> Martin Blaser: Thank you.

I call on Dr. Jungman.

>> Elizabeth Jungman: Thank you.

So echoing the thanks for the work, and I know that I in particular had a lot of comments

on many of the drafts, and so I appreciate the really collegial discussion about that

and appreciate that.

I was just kind of picking up on Ramanan's point.

The, you know, full funding of this report is, of these recommendations, is highly unlikely,

and there's a really, you know, a near future fiscal environment.

But even if it was in any circumstance where we are talking about using tax payer dollars

to fund private company activities, that's a big deal.

And accepting that the economic challenges here are really daunting, I think that's something

that, you know, we just have to take really seriously.

And so, you know, we need to really clearly identify what it is we're trying to incentivize,

and our basis for believing that that incentive works, and our rational for believing that

that investment will have more of an impact on spurring development than other options.

And so, you know, this report does that I think at a very high level.

And the next step, you know, for people who are taking this report and moving it forward

will be to, you know, to identify, you know, really some of the details here.

Like what are the specific vaccines that we want to pull out of the incentive structure?

You know, why don't we think that the market is adequate to, you know, reward a diagnostic

to couple with any given antibiotic?

Or you know, how exactly do market entry rewards work?

And so you know, this is, it's already 46 recommendations.

There's only so much you can do in a report, but just to sort of flag the next steps.

And so you know, I think one way to look at this report is it's a fairly high level -- I

mean there's a lot of detail, but still within any of these, for folks who've been involved

with discussions in any of these areas for a long time, it's a fairly high level, you

know, menu of options of things that could spur development.

And it will start I think as a good starting point for the difficult work to come for making

the case for any individual intervention.

So just a -- just adding that layer on.

Thanks.

>> Martin Blaser: And remember, our charge as scientists, as

practitioners in this realm is to come up with the most scientifically sound and feasible

ways to move forward in this idea.

We will rely on our colleagues on Capitol Hill to allocate the funds, and our colleagues

in the federal government to utilize the funds.

I was very pleased by a number of the reports in the last two days where the presenter said,

"Well we, considering PACCARB's recommendations, we have done the following."

So I'm hopeful that we will get a similar response in years to come.

Are there further comments?

So therefore I think it's time, Jomana, for us to take a vote.

>> Jomana Musmar: Sure.

Thank you Dr. Blaser, and thank you to our chairs for working with us on the development

of this report.

It's been a long time coming, and we've come to this day.

So in compliance with the Federal Advisory Committee Act, all deliberations of FACA advisory

committee seeking to reach consensus on advice to be given to the department are to occur

in a public meeting , such as this one, and consensus requires a quorum, which equals

half of the number of voting members plus one.

For the advisory council, for this one, a minimum of eight votes are required for the

passage of this report to the Secretary of Health and Human Services, Tom Pins [sic].

I will call on our voting members for their decision on the current version as it stands

right now on our website.

And for the record, please state either yay or nay when your name is called.

I'll start to my left with our first voting member, Martin Blaser.

>> Martin Blaser: Yay.

>> Jomana Musmar: Mike Apley, are you on the line with us?

>> Mike Apley: I am, and I vote yay.

>> Jomana Musmar: Thank you, Mike.

Helen Boucher?

>> Helen Boucher: Yay.

>> Jomana Musmar: Angie Caliendo?

>> Angela Caliendo: Yay.

>> Jomana Musmar: Alicia Cole, are you with us on the line still?

>> Alicia Cole: Yes, I am.

Yay.

>> Jomana Musmar: Thank you.

Sara Cosgrove?

>> Sara Cosgrove: Yay.

>> Jomana Musmar: Thank you.

Peter Davies?

>> Peter Davies: Yay.

>> Jomana Musmar: Thank you.

Lonnie King?

>> Lonnie King: Yay.

Yay.

>> Jomana Musmar: Thank you.

Kent Kester?

>> Kent Kester: Yay.

>> Jomana Musmar: Ramanan Laxminarayan?

>> Ramanan Laxminarayan: Yay.

>> Jomana Musmar: Thank you.

Aileen Marty?

>> Aileen Marty: Yay.

>> Jomana Musmar: Thank you.

John Rex?

>> John Rex: Yay.

>> Jomana Musmar: >> Tom Shryock?

>> Tom Shryock: Yay.

>> Jomana Musmar: In both senses of the meaning.

[laughter]

Randy Singer?

>> Randall Singer: Yay.

>> Jomana Musmar: And Bob Weinstein?

>> Robert Weinstein: Yay.

>> Jomana Musmar: Thank you.

The report passes through a unanimous vote.

>> Martin Blaser: Thank you, council, for all the work that

has gone into this.

I'm so -- I'd say we're all so indebted to our co-chairs for this process, to Dr. Weinstein

and Dr. Kester, to the co-chairs of the working groups, to all the working groups.

An enormous amount of work.

We have a product that we can bring forward into the realm of consideration.

And that's our job, and shortly we're going to start working on stewardship.

So you can take a deep breath for a few minutes and then we will begin again, but I just want

to thank everybody for a terrific job that's well done, and I'm pleased that we were able

to -- for us all to agree.

Good, good.

So, now it is time in this meeting for our public comment.

And as in the past, we will listen to any public comment.

Priority has been given to members of the public that have registered online.

We ask the commenters to limit their comments to two minutes or less.

As a reminder, this is not a question and answer period, only an opportunity to voice

public opinion.

All members of the public are encouraged to send in their full comments by emailing carb@hhs.gov.

And public comments emailed to the CARB mailbox by the deadline indicated in the federal register

and website are available at the registration desk.

So, I'd like to call on our first commenter today.

We have four people who have registered.

First commenter is Louis Mendelson from AllerQuest LLC.

Mr. Mendelson.

>> Louis Mendelson: Thank you very much to PACCARB for the opportunity

to present my comments.

I have been in the practice of allergy and immunology since 1972.

I've been involved with penicillin allergy research since that time.

I'm also from the same school as many of you, that it's better to put your seat belt on

before the accident, and not after the car accident.

AllerQuest is a small company owned by myself and two other allergists and a biochemist.

We formed this in 2005 when the previous manufacturer of PRE-PEN, the only penicillin skin testing

approved by the FDA, stopped production, and no other company would bring it back to market.

Therefore, no one would be able to test for penicillin allergy again.

Since bringing back PRE-PEN to the market in 2009, we have been working to improve the

product by expanding the panel of penicillin reagents in this test kit to identify even

more people who carry IGE antibodies against what are more penicillin determinatives.

Such tests are critical to antibiotic stewardship, understanding, and stemming antibiotic resistance.

Of course, while 30 million people are labeled as penicillin allergic, 90 percent or more

of these can currently take penicillin without risk of severe reactions.

Without penicillin skin testing, millions of patients are needlessly diverted to broad

spectrum alternatives, such as vancomycin or [unintelligible], which are associated

with a higher degree of infection [unintelligible], as well as a higher risk of clinical complications

along the hospital stage.

Recognizing these costs, the Center for Disease Control in 2016 issued a fact sheet for all

health care providers advising, "The use of broad spectrum antibiotics in patients labeled

as penicillin allergic is associated with higher health care cost, increase of antibiotic

resistance, and sub-optimal antibiotic therapy.

And encourage penicillin skin testing as a reliable and useful method for evaluating

IGE penicillin allergy."

A great number of public health institutions are joining CDC in recognizing the important

role that thorough penicillin evaluation can play in antibiotic stewardship.

The American Academy of Asthma Allergy and Immunology issued its first position statement

in 10 years to address the topic, strongly encouraging, when indicated, indicated from

the history, more widespread and routine performance of penicillin skin testing to reduce cost

of care, enhance patient safety --

>> Martin Blaser: Your time is just about up.

>> Louis Mendelson: Okay.

And improve outcome of care.

Penicillin allergy evaluation has been supported by the American Board of Internal Medicine,

the Infectious Disease Society, the Working College of Allergy and Immunology, and the

Society of Healthcare and Immunology.

We hope this analysis will provide awareness to healthcare providers that penicillin allergy

testing has potential impact on stemming antibiotic resistance.

I thank you very much for allowing me to say this.

>> Martin Blaser: Thank you.

I'd now like to call on Steven Roach from Food Animal Concerns Trust.

Mr. Roach.

>> Steven Roach: Yeah, I'd like to take us back to this morning's

discussion about prevention control.

So and again, as always I talk about animal agriculture.

So infection prevention in animal agriculture from our perspective is primarily related

to farm management practices that lead to the -- to disease.

In both cattle and swine production, co-mingling animals from different sources is still a

problem that is often addressed with routine antibiotics.

Most feedlot cattle receive macrolide antibiotics to address health problems created by inappropriate

diets.

We need practices that are associated with illnesses in both cattle and swine.

The poultry industry has made some changes by cleaning up their hatcheries, which has

resulted in them no longer needing to reuse antibiotics in the hatchery cases.

In many cases, economics drive these choices.

And many of these practices are based on access to inexpensive antibiotics to address consequences.

So when we talk about prevention, we also have to think about -- highly about economics

and animal agriculture.

In terms of federal agencies, there are several issues that I would like the council to take

into consideration.

First, there is no federal authority for on-farm food safety for meat and poultry.

FDA has authority over feed and drugs, but there is no authority for addressing human

pathogens on farms, either resistant or not.

So even if we have a multi-drug resistant outbreaks associated with animal products

traced back to the farm, is dependent on farms voluntarily allowing public health officials

access.

And there is no authority to require farms to take steps to control risks.

And the other thing that's a related issue is that we have no system in place to collect

actionable data on antibiotic use or resistant bacteria on farm.

Several council members are funded by FDA to develop systems to collect antibiotic use

data, but it is unclear whether these efforts will be sustained over the long run.

So these are short term grants.

USDA has some data collection programs, but I ask the council to explore whether the quality

of data collected by these USDA programs is adequate to identify problems and solutions.

Dr. Craig at CDC described CDC's efforts to create a system to detect, respond, prevent,

and innovate in human medicine.

I would say in animal agriculture, detection is rudimentary and the other three are nonexistent.

And a final comment is that Dr. Flynn mentioned lack of resources for some of these programs

within the FDA, but the agency has not requested the new -- in its budget request these new

resources.

So we do have a problem where, I'm kind of disturbed to see agencies saying we don't

have the resources, but if they're not requested, it's much harder to get Congress to actually

provide the resources.

So we really need the agencies to ask.

Thank you.

>> Martin Blaser: Thank you for your comment.

I now call on Amanda Jessick [spelled phonetically] from the Infectious Disease Society of America.

She does not seem to be here.

So I now call on Kevin Kavanagh, Health Watch USA.

Mr. Kavanagh, Dr. Kavanagh.

>> Kevin Kavanagh: Well, thank you very much.

As a recipient of bone morphogenetic protein to my neck, I feel the FDA's embracing of

an effort to increase the speed of approval for device drug hybrids raises significant

safety concerns.

In addition, I was concerned regarding AHRQ's presentation on chlorohexidine, especially

in light of the integrity issues which have been raised regarding the reduced MRSA study.

This was also a subject of a recent Reuter's investigative report by Deborah Nelson, which

centered on conflicts of interest and on FDA warnings against this type of chlorohexidine

use.

On the Health Watch USA website, there's a YouTube presentation by Matthias Mievault

[spelled phonetically], who raises serious concerns about research integrity problems,

including the recent meta-analysis, which is performed by the World Health Organization

for their current recommendations regarding surgical antisepsis using chlorohexidine.

And of course, you'll all remember the NQF chlorohexidine Charles Denim [spelled phonetically]

debacle.

All of this I feel is starting to form a pattern, which I feel needs careful evaluation, and

is also of significant concern.

Finally, it would be very interesting to have a world map which designates countries having

over the counter antibiotic sales, and to determine what percentage of the world's population

currently can obtain an antibiotic without a prescription.

Thank you.

>> Martin Blaser: Thank you.

Does anyone have any further comments?

Yes, please.

Please identify yourself.

>> Lisa McGiffert I'm Lisa McGiffert with Consumer's Union,

and a couple of comments about the report, even though I know you've already voted on

it, but as expressed by Elizabeth Jungman, Consumer's Union is also concerned with the

use of taxpayer money for private enterprise as envisioned by this report.

I'd like to also talk about post market studies.

Numerous recommendations to speed through FDA approval of devices and diagnostic tests

with a post market study.

These studies often don't start for years after the device is out there and they have

three to five years before reporting results, which could lead to many patients being harmed

or misdiagnosed without coming to the attention of the FDA.

So I recommend that we -- that you look into specifying that these studies begin immediately.

That is, in exchange for putting untested products on the market due to logistical problems,

like responding to a rare bacteria, the companies and healthcare providers using these untested

products should be required to sign an agreement to submit data regarding its use and results

as soon as it starts, and for that data to be looked at as you go along as far as the

results to make sure that patients aren't harmed and that they're actually working.

Thank you.

>> Martin Blaser: Thank you.

Do we have any further comments?

So that closes the period of public comment.

Now we go back to the council and ask does anyone have any final comments to make?

Hearing none, this meeting is adjourned.

Our next meeting is planned for January 24 to 25, 2018.

Please visit our website for all updates, including the final report from this council

from this meeting.

Thank you.

For more infomation >> PACCARB 7th Public Meeting Day 2, Pt 5: Council Discussion and Vote, Public Comments and Adjourn - Duration: 24:46.

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[NEWS]Boris Johnson wants PM to deliver public sector pay rise – funded by layoffs - Duration: 3:25.

Boris Johnson wants PM to deliver public sector pay rise – funded by layoffs

BORIS Johnson has called on Theresa May to give five million state employees a good wage rise – but pay for it by cutting their number.

The government should also act to increase the poorest private sector workers' wages, the Foreign Secretary said.

Boris Johnson has called on Theresa May to give five million state employees a good wage rise – but pay for it by cutting their number.

The Foreign Secretary has said the current minimum wage of £7. 50 an hour - rising to £9 by 2020 - is not enough.

The current minimum wage of £7. 50 an hour - rising to £9 by 2020 - is "not enough", he insisted.

The two controversial declarations will be seen as another challenge to the PM's authority, as pay levels are outside of his Foreign Office brief.

In an interview ahead of the Tories' annual conference on Sunday, Boris told The Sun: "I want people to be paid more. "People get up unbelievably early and they work unbelievably hard, they deserve to be properly paid.

Quizzed how he would come up with the billions needed to break the current 1% wage rise freeze, Mr Johnson suggested cutting the number of state-employed staff. He said: "You can pay people more, but shrink your wages bill.

"I'll be honest with you. I do think you can always find ways of reducing expenditure on things that are not necessary. "Any minister who tells you you can't find savings, it is not true.

The government can also "help people" laid off in any new public sector cull into jobs in the flourishing private sector, Boris added. He said: "There has been a huge expansion in the private sector jobs in the UK economy since 2010.

Chancellor Philip Hammond is under massive pressure to end the seven year-long austerity pay cap and award inflation-linked rises to state workers such as teachers, nurses and soldiers in his Budget in November.

In an interview ahead of the Tories' annual conference on Sunday, Boris told The Sun that he was 'people to be paid more'.

Mr Johnson also issued a warning to the Tory party not to shift to the left in a bid to win back some of Socialist Labour boss Jeremy Corbyn's cult popularity.

On the current level of the minimum wage, Boris said: "We brought in a National Living Wage.

"I think that is the right thing to do but it is obviously not enough, and I would of course see people getting decently rewarded for their hard work. I really believe in that.".

Mr Johnson also issued a warning to the Tory party not to shift to the left in a bid to win back some of Socialist Labour boss Jeremy Corbyn's cult popularity.

  Theresa May forces Boris Johnson and Philip Hammond to team up over Brexit.

Instead, he called on Conservatives to be "more courageous" about making the argument for the free market, engage "mano a mano" in the fight, and "find new ways of invigorating people about our ideas".

Boris added: "It would be a mistake for us to go chasing after Corbyn down some leftist cul de sac. "He is bathing in this orgiastic adulation from Corbynistas who are conspiring in this myth that he won the election.

"Young people don't have to go back to the 1970s. You don't have to time travel, you just have to travel round the world – Venezuela.".

The way to tackle Mr Corbyn's assault on capitalism is to "make markets work better for people", he also insisted. Boris added: "We need to be courageous about making our arguments.

"We have got to be engaged mano a mano with all this left wing nonsense which has been peddled again and we have got to find new ways of invigorating people about our ideas".

For more infomation >> [NEWS]Boris Johnson wants PM to deliver public sector pay rise – funded by layoffs - Duration: 3:25.

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Celebrity New : International sportsman 'defended two gay men' in public brawl - Duration: 3:23.

International sportsman 'defended two gay men' in public brawl

An England cricketer who has been arrested after an alleged brawl was defending two gay men, it has been claimed.

Ben Stokes, 26, was taken in by police in the early hours of Monday morning after the incident, and will not be considered for selection for England until further notice.

But according to Piers Morgan, Stokes was responding to homophobic taunts thrown by two men at two others in Clifton, a suburb of Bristol.

The chat show host, who is friends with several high-profile cricket players, has reported that Stokes "intervened to help two gay guys who were being abused by yobs, one of whom was armed with a bottle.

"Stokes has told friends he was incensed by the homophobic taunts, then saw the bottle being raised & decided to defend himself.

Morgan, who visited a gay club last month despite making repeated hateful statements about non-binary, genderfluid and transgender people, said Stokes obviously regrets what happened. But, Morgan added, Stokes view was: They started it, I finished it. I was protecting those guys..

The TV presenter said police were aware of Stokes version of events and are now trying to find the two gay men, to corroborate what hes said.

Morgan added: Stokes has told friends: The guy had a bottle in his hand & was threatening us, was I supposed to wait until he smashed it in my face?. A 27-year-old was also taken to hospital with facial injuries.

The BBC has reported that the cricket star – one of Englands best players – was fragile and devastated. He has since been released under investigation after being arrested on suspicion of causing actual bodily harm.

The player, who is Englands vice-captain, has a broken finger and has apologised to the England and Wales Cricket Board.

A spokesman for Avon and Somerset Police said: "The disorder which occurred on Queens Road, Clifton, at around 2. 35am on Monday continues to be investigated by officers, according to the Bristol Post.