Modernization Hub

Modernization and Improvement
2016 EIS Conference Langmuir Lecture

2016 EIS Conference Langmuir Lecture


>>I would like to now
introduce our CDC Director, Dr. Tom Frieden who will
introduce our speaker. [ Applause ]>>Thank you very much. And thank you for being here. This is a great event. We have the Langmuir lecture. I think of it as really the keystone event of each year’s EIS Conference. Last year, Jeff Dean challenged
us all to open data more for the public domain. And I think we need to make
more progress in that area. But it’s a good marker
to have set. So I’m really delighted. As you know, Alexander Langmuir
founded the EIS program. We are all in some very
important conceptual and philosophical ways
descendants of Langmuir in the work that we do. The work that says,
we don’t do things because we always
did them that way. We don’t do things
because someone told us to do it that way. We do things because that’s
where the data drives us. Now, I’m also absolutely
delighted to introduce Dr.
Margaret Hamburg as the Langmuir lecture honoree for this 65th annual
EIS Conference. Dr. Hamburg is an
internationally recognized leader. She currently is a
foreign secretary for the National
Academy of Medicine, formerly the Institute
of Medicine. She, as you know, most recently
was Commissioner of the Food and Drug Administration
where at the beginning of her term she set a clear
marker that she was going to further infuse a public health perspective into the Food and Drug Administration,
and she absolutely did that. I can say without a moment’s
hesitation that the interactions between CDC and FDA
are more positive today than they’ve ever
been in the past. And that’s to a great extent because of Dr. Hamburg’s
leadership. And because of that, we’re
able to do a lot more together than we could do as
individual agencies. She was known for
advancing regulatory science, modernizing regulatory pathways,
and increasing the globalization and reach of the agency, most fundamentally
committing to infusing that public health perspective. Before this she was the
founding vice-president and senior scientist at the
Nuclear Threat Initiative, a foundation dedicated to
reducing nuclear, chemical and biological threats. She also was previously
Assistant Secretary for Planning and Evaluation at HHS. And I will say perhaps
most importantly to me, my first boss, as the Commissioner of the New
York City Health Department, a wonderful health department which Peggy led wonderfully
for many years. I have always found her to be
an invaluable source of advice, wisdom, kindness,
intelligence and knowledge. Her title today is “From
Antibiotic Resistance to Zika: Reflections on Working at
the Intersection of Science and Public Health Politics”. Now I will say, Peggy and I have
both worked in New York City at the national level
in the U.S. and globally, and public health is like
politics to a great extent, the art of the possible. This is an intersection that is
both one of the most fascinating and one of the most
frustrating parts of our job. But it’s one that
we can’t ignore. Because as Bill Foege said last
night at international night, every public health decision is at some level a political
decision. And therefore, our role is
to ensure that the likelihood that the right decision
is made is maximized. But a common thread there
is that we need to ensure that the right information
gets to the right people in the right format
at the right time so that the right
decision will be made. Please join me in
welcoming Dr. Hamburg to CDC. [ Applause ]>>So thank you very much. I appreciate that
kind introduction. And it really is a great
pleasure to be here. I’m very honored to be giving
the Alex Langmuir lecture and to participate in what I
understand is the 65th annual EIS Conference. That is an impressive number, so
slightly older than I am today. It’s a wonderful opportunity for
me to recognize the importance of the work that all of you do. And also to reflect a bit on
my career in public health. And I probably won’t get
quite as much into some of the behind-the-scene politics. It might be fun, but I
still want to be discreet. I understand that
the overarching theme of this year’s conference
has been data for action. Starting with Dr.
Frieden’s opening remarks as the conference began I
understand earlier this week, and of course, you know, this is such an appropriate
and essential focus. And it’s one that I know that Alex Langmuir surely
would have approved of. His career was characterized
by his commitment to scientific rigor, strict
standards for data generation and analysis, and the importance
of disseminating and acting on public health information. And as you likely know, his
first great contribution to the fledgling CDC way back
in the late 1940s and early 1950s was to bring new rigor to malaria control activities here in the southern United States, which was then the priority
of the organization. And he insisted that malaria
cases be reported on the basis of positive blood smears,
enabling the program to be built on a foundation of accurate
and meaningful data for action. And so he solved
the malaria problem. And then he went on to define
for the nation and really for the world the
critical need and role for skilled epidemiologists
to respond to public health
threats, great and small. And of course, he began the
now much revered Epidemic Intelligence Service. The EIS program commands a very
special role in public health. And you all belong to a very
special and influential club. I will confess that early in
my career I almost applied. Don’t know if they
would have taken me. But before doing so, I had
the opportunity to meet with the late Carl Tyler,
who I think was then the head of the epidemiology program. I wanted to learn more, and
I inquired about whether if accepted I could do my
training in the northeast because my boyfriend,
now husband, was working in New York. And he wasn’t all
that enthusiastic about moving just anywhere. His response was
not encouraging. Actually he looked me
right in the eye and said that if he had anything
to do with it, if I asked for a
specific region, I would almost certainly
not be assigned to go there. So I guess that they like to
toughen you up in this program. But at least he was honest. So I never made that
special journey from clinician scientist
to epidemiologist. But I’ve always felt a kinship to and a deep appreciation
for your work. I’ll admit that some of my best friends are epidemiologists, wonderful, outstanding members of your ranks. And somewhere along
the arc of my career, I did assimilate the critical
concept that not everything that was important
for health happened in a clinic or a hospital and that populations, as distinguished from patients, were important. When I first became health
Commissioner in New York City, my great Aunt Winnie, who was
sort of like a grandmother to me, was very disturbed that I was throwing
away my medical career to become Commissioner. Why can’t she just
be a real doctor, she complained to my father. He tried to assure her that
I was still a real doctor, but now I had some
eight million patients. She didn’t feel all
that much better. But I came to understand in profound ways what
that really meant. And when years later I moved
on to the role of Commissioner of the Food and Drug
Administration, I gained new insights, just as I also gained several
hundred million more patients. So as I speak with you this
morning, I want to build on the theme of data for
action and address some of the public health challenges
I faced over the course of my career, and some of
those that lie before us. I know that Alex Langmuir
believed in brief, polished presentations, followed by equal
time for discussion. I look forward to our
discussion, but please forgive me that my comments may not
meet Dr. Langmuir’s standards for precision and
scientific rigor. Though perhaps after you’ve had a full week of such presentations, you may be ready for a somewhat
less structured approach and I don’t intend to
show a single slide. I guess that I really have to
begin with a story about data for action that was truly
formative for me in my career, and I dare say for
Tom Frieden as well. I do like to tease him by saying
I gave him his first real job in public health, launching
what has been and will continue to be a brilliant career. He probably would have
done okay without me, but I still do like
to take credit. And this story I think is a
great illustration of a number of things that I want
to talk with you about this morning, and it relates back to the work that Alex Langmuir
did with malaria. In the early 1990s, when I first
became health commissioner, New York City had one of the highest case rates
of TB in the country, in fact, five times
the national average. And New York City
accounted for close to 18% of the nation’s total cases. Notably, case rates had
been increasing since 1979. But somehow this had been barely
addressed as the city grappled with the growing
challenge of HIV AIDS, which though intermittently
intertwined with TB, seemed to overshadow the
threat of TB itself. But a smart enterprising
EIS officer working in the department
noticed this problem and wanted to learn more. He undertook a study
documenting a one month sample of TB cases in New York. He looked at the sputum
and found that the rates of drug resistance
were astoundingly high. Forgive me, Tom, if I don’t
get the numbers quite right. But the data showed
that nearly half of patients previously
treated for TB were resistant
to one or more drugs. And nearly one-third
were resistant to isoniazid and rifampin. Among patients with
first time TB, nearly one-quarter were
resistant to one or more drugs, and about 7% were resistant
to isoniazid and rifampin. It was clear that the treatment
regimens we were routinely using were increasingly
ineffective, and in fact, were likely making things worse. Needless to say, I was
profoundly impressed by this data and
the action needed. I was also impressed
by the young man who did this pivotal study,
Tom Frieden, of course. He was finishing up with
EIS, and I quickly hired him to direct the city’s
tuberculosis control program. Strikingly, before
he took the job on, the position was part-time,
just one reflection of the fact that TB was then viewed,
data notwithstanding, as a declining public
health problem. And a real complacency
had taken hold. With Tom’s new evidence in
hand, we were able to mobilize. The magnitude and urgency
of the problem was clear, and the New York Post
headlines screaming, “Killer TB on the Subway”
helped us as well. But it was a little
less scientific and perhaps a bit
more sensational. Looking back, I think
it’s fair to say that when Tom accepted my job
offer he probably didn’t fully appreciate what he was
getting himself into. That full-time job turned
into a round-the-clock battle against a growing epidemic. But no doubt it was good
preparation for Ebola and Zika and so much more. And it certainly, I
think, affected my thinking about public health, and
I suspect his as well. As we set out, many
were discouraging. Wise people in the world of
public health cautioned me that we’d make little progress
because TB was so associated with poverty in the underserved. If we couldn’t cure
poverty, we couldn’t cure TB. But we’re able to put in place
a well-designed data-driven strategy with a comprehensive
approach, adequate resources and real political backing
from the mayor on down. It took political and
public health leadership. It took an integrated
systems approach that engaged the homeless
shelters and jails and prisons, just as much as the
city’s physicians, clinics and hospitals, so that patients
needing treatment didn’t fall through the cracks. And it took a blueprint
for action that clearly defined priorities,
goals and objectives. And, the specific
responsibilities of the various players involved. And after only a few
years, we were able to see the TB numbers
in the city plunge. In fact I think far more
quickly and dramatically than we had ever
really imagined. Over a five-year
period, I believe, the TB cases dropped
overall by about 46%, and some 86% for
resistant strains. The complacency and
mistaken assumptions that led to the TB resurgence and the
lessons we learned in developing and implementing a
comprehensive treatment and control plan remain
for better or for worse, just as relevant today as they
were more than 20 years ago. And now, after many
years of working at the perilous intersection of
science, medicine, public health and politics, particularly
in New York City and then at the FDA, I’ve had a lot
of opportunity to grapple with difficult problems. And the chance to learn
sometimes by disaster, a lot about how to try and
traverse complex landscapes and sometimes stormy seas. From early on I gained
some important insights, obvious ones, like the fact that not everyone’s
going to like you. I quickly developed a thick skin and a strong stomach,
I would say. I learned to try to
always communicate clearly and honestly, but also to listen, to surround myself
with good people, and to seek out the
expertise needed. Correspondingly to
never be afraid to acknowledge what
I didn’t know. You may have to ask awkward
questions, but you have to get the best information you
need for the decisions at hand. And always, always, always to
use the best available science and evidence to inform
your actions. As I was reflecting
on this meeting and what I might talk about, I came across an article
written several years ago by Harvey Feinberg, a former
dean of the Harvard School of Public Health, and
immediate past president of the National Academy
of medicine, what was formerly known as
the Institute of Medicine. And as Tom mentioned,
I’m now serving part-time as the foreign secretary
for that organization. And so I took a special interest when this article called “The
deadly sins and living virtues of public health”
crossed my desk. It begins with a
more historical, in fact ecclesiastical reference
to the seven deadly sins of lust, sloth, gluttony,
greed, wrath, envy and pride, quoting Pope Gregory the
First in 590 AD as his source, but he quickly moves on to the
modern era using this litany as a foil to suggest there
are also seven deadly sins of public health. He kept three of the original
sins: sloth, greed and gluttony, but he added four more:
ignorance, complacency, timidity and obstinacy. And I suspect that we could all
come up with other candidates to replace or add to the list. But being an optimist at
heart, Harvey suggested that we might also think
about whether there are seven or more living virtues for
public health that can serve as a counterweight
to the deadly sins. He suggested some candidates:
Moderation, Prevention, Preparedness, Empathy,
Science and Service. To that list I’d like
to add Integrity. For me, integrity is such
an essential foundation for everything else. Integrity of leadership,
integrity of systems, integrity of science
and data, of course, and integrity of actions. The late Senator
Kennedy once said that integrity is the
lifeblood of democracy. I think that is true. And I think it’s
also the lifeblood of what we do in public health, what we must stand for
and how we must act. While at FDA I had
many occasions to think hard about
these issues. To be honest, when
I began at the FDA, I did not appreciate
the full dimensions and demands of the job: the vast scope of
the responsibilities, the diversity of highly
engaged stakeholders, the competing priorities, the limited resources, the fish bowl environment
in which FDA works, the complexity of
the science required, and the growing complexity of the products we were
responsible for overseeing, not just the science and
engineering of the products, but also the increasingly
complex and global supply chains that they followed from initial
development and production into our homes and hospitals. As I quickly came to
understand, the FDA is charged with an enormous and
significant task: to promote and protect the
health of the American people and increasingly people
all over the world. It’s a science-based,
data-driven regulatory agency with a public health mission. The responsibilities include
efforts to ensure the safety, effectiveness and quality
of human and animal drugs, vaccines, medical devices,
the safety of the blood supply, oversight of cosmetics
and dietary supplements, as well as the safety
and wholesomeness of the vast majority of
our nation’s food supply, including nutrition related
standards and guidance. And during my tenure,
FDA also took on the regulation
of tobacco products. All-in-all, FDA regulates
products that account for between 20 and 25 cents of
every consumer dollar spent on products in the
United States, and products that people
really rely on in fundamental and often life-saving ways. The agency’s mission also
includes working proactively to foster scientific innovation
that will lead to new, better products and enhance the
safety and benefits of products that are already
in the marketplace. And in addition, FDA is
charged with providing accurate, clear and actionable
information to the public about these products
and their use. It’s been said that
no other agency in the federal government
touches more American lives every day more often than the
FDA in every American home, at every table, in
every medicine chest, in every hospital, pharmacy,
grocery store, doctor’s office, school cafeteria, restaurants and distribution chain along the
way from all around the globe. It is a lot. To again quote the
late Senator Kennedy, one of our nation’s
greatest champions of health, he once said that the FDA is
the most important health agency in America. And I suspect that some of you
in this room are, you know, wondering about that
a bit, you know. Absolutely the CDC plays an
essential and critical role, and you’ve co-opted the tagline:
“Working 24/7 to Protect America from Health and Safety Threats”. But the truth is that
we’re all in it together. And there’s more than
enough work for everyone. And we’re all more effective
when we work together. I think we must also share
a relentless focus on and commitment to the
integrity of our work and all its many aspects. Certainly while I was at the
FDA I was struck by the fact that building and maintaining
trust and confidence in the agency in
our integrity had to be the linchpin
of everything we did. Unfortunately, when I
took over the helm at FDA, public confidence in my
agency had taken a number of serious hits as Congress
and the media had really piled on following a series
of drug safety concerns and foodborne outbreaks. And as the agency
grappled with the impact of decades-long underfunding,
one thing I learned was that when people did
not understand the FDA or its actions, they
often assumed the worst. Only by really explaining
what we do, how we do it and why could we foster that
necessary trust, even in times of conflict or controversy. We worked hard to promote a
culture of greater openness, shaping an agency that took
its leadership role seriously, listened to our stakeholders and
endeavored to foster integrity and clarity in all our
systems, procedures and working relationships,
as well as in our decisions. But earning and maintaining
the trust and confidence of the American people in the FDA must also
be inextricably linked to real integrity in the
science that underlies the work. The public and policy
makers must understand that FDA makes decisions based
on the best available evidence. This is not always easy,
but frankly when trying to navigate complicated
waters buffeted by politics, stakeholder pressures and so
much more, knowing that science and data must be your North
Star, is the only thing that keeps you on course. It may not always endear
you to your colleagues or satisfy adversaries,
of course. Unfortunately for me, I often
had to take visible stands, sometimes at odds with
the Department of Health and Human Services or the
White House or Congress. I certainly did shed
some considerable blood in the halls of Congress. But I didn’t regret it because
the principles were real, as were the implications
for patients, consumers and public health. Plan B was one such example. This was the so-called
“morning-after” pill, which had actually been the
subject of controversy and cries of political intrusion, when
the Bush Administration failed to act. It came back to FDA
while I was there with additional studies done
to support the application to be sold over the counter to
females of child-bearing age. The data and studies met
the criteria for approval, and approval was the FDA’s
unwavering recommendation. However, with other
considerations in mind, the FDA decision was overruled, the intrusion of politics
once again, I’m afraid. But the Secretary of Health and Human Services had
the legal authority to make the final decision. Yet it was an action
with few precedents, and to my mind worrisome
on many levels. At the time, some thought that
I should resign in protest. But my calculus was that I
had to make my position clear, defend it, but stay
on to help the agency through other important
issues and other battles that I knew would come. The good news was
that I was allowed to publicly define the
position of the FDA, and no other science
was produced that counters the scientific
determination the FDA had made. And in fact, the court
decision subsequently led to plan B becoming
available over the counter as we had recommended. But speaking frankly, what
was additionally troubling to me were comments
from the White House that included the observation that FDA should use a
quote/unquote “common sense” criteria for regulatory
decisions. I understood what
they were getting at. But really? Whose common sense? And in this political season, I think the thought is
particularly frightening. [ Applause ] So I dare say that one person’s
common sense standard might be another person’s
poison, and for the FDA, that might in fact be literally. The episode passed, but
it was reminded to me how in so many important areas of
public health it can be easy to say,”just follow the science,” but mightily hard to do. How fragile is the
hold sometimes? And you can see the
slippery slope. Certainly reality
demands flexibility, but we must be honest
about what needs to be done and address it based on data, not what is comfortable or politically desirable
or opportune, and not what the loudest
voice in the room demands. During my career, reproductive
health, sex education, violence prevention and HIV AIDS
have all provided complicated challenges where science
and what really matters for people had to
be the guidepost, but the going has
often been rough. The same is true for issues like
trans fat and sodium reduction or obesity and tobacco
prevention and control. Where the concerns of stakeholders may
be rather different, but the pressures
no less forceful. In this context I want to say a
little about science at the FDA. One of my top priorities as
commissioner was to support and strengthen science,
both within our walls and to engagement with a
broader scientific community. When I first arrived, I
was amazed by the quality of the FDA scientists
and their dedication. But it was also striking how
much more needed to be done to enable them to undertake
their important work. To be honest, many
on the outside, including budget appropriators,
but also some research advocates as well, really think
that science at the FDA is mainly checklist
science, rotely going through the Sunday requirements and standards for
product review. But really it is
just so much more. It requires a real depth of
understanding and breadth of knowledge to assess
whether an intervention works, to assess the risks
and benefits, to evaluate short-term
impact and long-term effects. It requires real skill to
help ensure a streamlined and effective research
and development plan to foster the timely but
scientifically rigorous study of a candidate product and
its translation from bench to bedside or from farm to fork. FDA scientists must truly
understand what it takes to move from a good idea to
a real world product that, yes, will bring
positive benefits to the people who use it, but also that it’s
stable, reproducible, and can be reliably scaled
up, manufactured and used. Strong science-driven regulations also require the ability to respond to changing
situations, new information and
new challenges. We can’t have a
one-size-fits-all approach, but we must always bring the
best possible science to bear. While always fundamental,
this comes into stark relief when confronting
an emerging crisis, such as we recently
dealt with with Ebola and now, of course, with Zika. How do you responsibly move, promising a much needed
product, drugs, vaccines, diagnostics, protective gear,
etcetera, that are still in the earliest stages of
development and testing out to the populations
who desperately need them? And how do you undertake
the necessary research, logistically, ethically and with
appropriate scientific integrity and rigor? I think we’ve learned a lot, but this is an arena
of scientific work, capacity building
and collaboration that still urgently needs
to be developed and refined, and where success will
require that we work in teams across disciplines and sectors, across levels and
agencies of government, and across nations. And in my view, both
the crisis setting and routine needs demand that
we advance regulatory science. The knowledge and tools
necessary for the meaningful and timely review of products
for safety, efficacy, quality and performance
and to inform more efficient product development. We need to combine
greater understanding of the underlying method of
disease and human biology with new technologies
and scientific advances in this effort, including such
important areas of R and D as predictive toxicology,
identification and validation of biomarkers, innovative
clinical trial designs, and bioinformatics including
modeling and data mining. Such efforts can help us
leverage opportunities for innovation and more
quickly close the gap between scientific discovery
and real world products that will make a difference for
people and for public health. Yet it’s a component of our
overall scientific enterprise that has been dangerously
underappreciated, underdeveloped, and underfunded. It isn’t generally
sexy discovery research for NIH to fund. Companies have been reluctant
to take on broad studies which can be expensive,
time consuming or risky when they need to focus on the specific products
they’re developing. But at the end of the day, such regulatory science research
can benefit whole categories of products or domains
of research and serve as the true translational bridge
for an important discovery to a product that
will change lives. And without focused
informed attention to this, the integrity, value and return
on investment of our system for biomedical research,
product development and ongoing product assessment
and oversight for both food and nutrition and
for medical products, will be seriously compromised. And I think this is an
arena where in fact the work of epidemiology also has
a critical role to play. One certainty for FDA is that
it must always be building out its evidence base. But for any given decision,
how much evidence is enough? What kind of evidence? Who collected it? And under what circumstances? What is an acceptable
level of uncertainty? These are all questions that
complicate the job of the FDA. And these same questions, this
same predicament is not lost on those of you in the room,
those working in settings like the CDC or state and
local health departments or in other areas of public
health and medical care. It’s a struggle that we all
share, no matter what aspect of public health
you’re pursuing. Certainly its foundational
to the EIS program that thoughtful investigation,
careful data collection and rigorous statistical
analysis, the scientific process must
underlie problem solving. Anecdotes, wishful thinking
and powerful personal or professional convictions
cannot substitute. And if I want to be snide
I would add polling data or other vested interests. Sometimes we have all
the data that we need, but other factors
get in the way. And certainly plan
B was one example. But unfortunately we don’t
always have all the data that we want or need at the time
the decision has to be made. And sometimes there’s
intrinsic uncertainty. I’m sure that Tom and his team
didn’t have anywhere near the information they wanted when
recommendations about the risks of travel and pregnancy
were being called for in the early days of Zika. In a very different context, we face similar dilemmas
working together on foodborne and other
product-related outbreaks. When to pull the trigger
and initiate a recall? and questions of Is it
too soon or too late? Too aggressive or not
aggressive enough? And on medical product
evaluations at the FDA we always felt
pilloried between two extremes, two speeds of approval,
too fast and too slow. We wanted too much
data or not enough. We accepted too much
risk or not enough. The pendulum historically
tends to swing back and forth, but the main struggle in this
regard that I had to cope with was the perception that FDA
was the barrier to innovation. And I think this was spurred
on by the anti-government, anti-regulatory climate that we
are working in today as well. But many believe that
it was our cumbersome and bureaucratic requirements
that were preventing all kinds of treatments and cures
from flying off the shelves to the patients and public
that needed and wanted them. But believe me, for example, it’s not FDA’s excessive
regulation and unduly demand for data that’s preventing
effective treatment for Alzheimer’s disease
as some have claimed. The problem is gaps
in the science. We don’t adequately understand
the underlying mechanisms of the disease, how
best to target therapies and even how to
diagnose it, particularly in the earliest stages. Nonetheless, the FDA
continues to face calls for lowering regulatory
standards and for other forms of deregulation in order
to advance innovation. But let me stress, especially
in the context of integrity and science, that rigorous
science is not an obstacle to innovation. It’s the foundation
for real innovation. We sometimes forget
that in the race to find new treatments
or intervention. But innovation is only
meaningful if it works. If we rely on sloppy
or inadequate science, we may get new products onto
the market more quickly, but we’ll have no idea
whether they really work, whether their benefits truly outweigh their
risks to patients, or whether they’re better or
worse than existing products. And frankly, in this
era of cost constraints, who’s going to want to
pay for these products? Hovering in the background
of some of these debates
is the considerable and legitimate concern these
days about the reproducibility of scientific research
studies and evidence. In fact, I think if you read the
media you’d think that science in this country was in the midst
of a replication failure crisis, but I think we need
to respond with care. For the FDA, few things matter
more than data integrity and the quality of evidence used
to make regulatory decisions. FDA makes very significant
decisions for people and for society. Moreover, many FDA regulatory
decisions end up in court with challenges to the
evidentiary standards. For these reasons, great
attention is paid to data and its sources and care
taken to review, analyze and compile the available
data with the utmost rigor. One little known
fact about the FDA, and in my view one
real strength, is that the agency
actually requires review of the patient-level data for
clinical studies that are part of a new drug approval
application. This means that you’re
not relying on someone else’s analysis and
presentation of the findings with all the possible
attendant concerns. FDA has a very specific
legal regulatory framework for evidence standards
and decision making. But many of the challenges
that we face are no different than those of you working in
other public health agencies or in academia or elsewhere. Trust and confidence and
the reliability of the data and the level of certainty about
the findings really matters when assessing problems
and making decisions. But stepping back a bit,
several important issues emerge from these discussions
about research replication, data quality and the
presentation of findings. I suspect that some
of these issues may be on your minds as well. First, I do think that we must
guard against the tendency of some to immediately
conflate replication failure with fraud or falsehood,
especially in areas of complicated or
emerging science. Failure to replicate may
have to do with getting some of the basic conditions
and techniques right. It may have to do with
inconsistencies or differences in systems or settings. It may have to do with flaws in
study design or interpretation which raise broader questions
about study findings. Or it may be deliberate fraud. I’m not saying that
any of it is good, least of all data
manipulation or outright fraud. But whatever the cause, we must
continually strive for better, more transparent and
reproducible data. The best way to address
it is to delve more deeply into the scientific
questions at-hand. But I worry that
for some the rush to judgment is intentionally or unintentionally diminishing
the value of evidence. I think that we’re also
increasingly confused about the role of failure. Failure comes with the
scientific process. Hard to imagine a world in
which we could have great breakthroughs and discoveries without some failure
along the way. But our systems aren’t
designed to accept this. Success, not failure,
is rewarded. And so much so that negative
studies are generally not published or shared. And information with great
value for future research or other actions
doesn’t get shared. At FDA, there are
actually legal constraints that prevent information about why a product
did not get approved. It can’t be made available
without the expressed permission of the company who often
doesn’t want to do so. But sadly, what this
really means is that broader research
communities can’t benefit from important insights,
and sometimes later R and D efforts head
down dead ends that could have been avoided
at the expense of money, time and most importantly,
patience and public health. So we’re not building
systems that really serve to advance science in critical
ways and that ultimately help to better deliver that science
in the service of the public. So one last thought
in this domain. We must find ways to more
effectively share data. In some instances,
data sharing will help to verify earlier findings and
will help address the problem of research integrity, both
replicability and credibility. But enhanced data sharing
can also foster additional scientific progress and better
use of existing studies. Important secondary research
questions using existing data can be examined. Or as new scientific
insights emerge, shared clinical databases may
enable the use of data mining to go back and look at critical
questions like subgroups of responders based on a
particular marker or those that are more likely to
suffer serious side effects. Meta analyses of shared
published data done right can elucidate new recognition
of safety concerns, further information about how
well a treatment works and lots and lots of other important
contributions. I’m not naive about the
complexity of data sharing in these undertakings,
from patient consent and privacy issues to developing
the data use tools, standards, analytics and agreements
that are needed. The operational questions
of data control and access, authorship
credit, quality control and financial support needs. This is not a
straightforward task. Nonetheless, it clearly
represents an evolving and important advance in the
conduct of research and one in which we all must participate and make sure that
we do it right. But you are all the
data experts. With the training and experience
the EIS program has provided, few understand better than
you the importance of data, how best to collect,
analyze and act on it. Despite all the uncertainties
in the world around us, one thing for sure is that
your skills will be needed. Public health epidemiologists
will be called on to address persistent
and emerging challenges. You’ll be needed
to study some of the most complex
problems of our day. New analytic tools and approaches will
expand your repertoire, just as the dimensions of the problem before you
will also grow in scope, complexity and likely
urgency as well. You’ll be asked to work
across disciplines, sectors, levels of government,
and across borders. But whatever the setting
and whatever the task, I trust that you will bring to
it both the scientific rigor and the responsiveness that
has long characterized the EIS and that you’ll do
it with integrity. Thank you. [ Applause ]>>Alright. Now is the period for equal time for
discussion, right?>>Alan Block, EIS 1980. I’m a big admirer of you and Tom
for the outstanding job you did on MDRTB in New York City. My question on data for
action relates to multi-drug resistance related
to livestock products. When the question
that’s always asked, what drugs were given
to these livestock? The answer is we
couldn’t find out. The livestock owners
don’t have records, and it’s like we’re
being stonewalled. And I think we may need to have
some input from people outside of the Public Health
Service and, for example.>>Can I just respond
to what is being done? Because I think you raise a set
of critical issues and how best to intervene and
probably the need for intervention on many levels. But real actions are underway
with respect to the use of antibiotics in the
animal husbandry area, the raising of livestock. FDA is in a process of making
it illegal to use antibiotics of importance for human
health, for growth purposes in animal populations. And that’s a very, very
important first step. Secondly, the use of antibiotics
in animal populations is coming under the oversight of
the veterinary community in a way that, as you point
out, it hasn’t been before. As you probably know, antibiotics are delivered
very differently in the farm and animal husbandry context
than in the human context. And there really hasn’t
been adequate information about what’s being used,
by whom and to treat what because it’s combined
in the food. And you could just go into the
store and basically buy it. So that is now being
brought under the oversight of veterinarians so
that we will be able to have much more
definitive information, and hopefully, you know, a much
better sense of what’s going on as we are seeing
the use of antibiotics for growth promotion
being phased out. Importantly also there
are efforts underway to strengthen the ongoing
surveillance of the linkage between use of antibiotics
and animal populations and human populations
and patterns and trends in antibiotic resistance. And that is a coordinated effort
involving CDC, FDA and USDA. It’s an underfunded
domain, and I hope, I don’t know what
happened to some of the recent budget
requests in that area. It’s an area where advancing
science can help us do a better job in terms of
molecular typing so that you can really
track better. Because it’s been
hard to really define in some instances the
relationship between the use of antibiotics in
animal populations and the actual development
of resistance that has affected
human populations. But work is going
on in that area. There’ll need to be more. I think that there is newfound
recognition and attention to this problem, which hopefully
will translate not just into announcements of concern,
as we’ve seen for many years, but also real sustainable
action that targets where changes need to made. But I think there is progress. So let’s go to the
next question.>>My question.>>Do we have time
for everyone please? Let’s go back here.>>Thank you for your
presentation and your frankness. Konrad Hayashi, Division of Preparedness and
Emerging Infections. For many years there
has not been any means of really assuring that food
supplements, vitamins, etcetera, are not just, not harmful, but really provide any
significant benefit. How do you see the
potential for moving forward so that there is any sort
of true data-driven proving of effectiveness for
American consumers?>>Well this is an area where
FDA has an oversight role but limited authorities
in terms of aspects of product regulations
that are seen in domains such as drug review
or medical devices. I would say the American
people believe that dietary supplements
are reviewed by the FDA just as drugs are. But in fact, the law
gives FDA authority, and the law is fairly recent I
would add as well, but authority to do inspections for good
manufacturing practices. And the law requires that serious adverse
events be reported to the company and to the FDA. But certainly we have
seen many, many concerns of dietary supplements ranging from them not actually containing what they purport to contain to containing products
sometimes serious drugs that they don’t list
and shouldn’t have, and the consumer doesn’t
know that they’re getting. In an increasingly
globalized world, many of the dietary supplements
are coming from places where there are many fewer
standards and measures to assure production, quality
and safety of supply chains. And that adds an additional
dimension of concern, and many of the dietary
supplements are coming in whole or in part from outside
the borders. So it is an area where I think
continuing data about the types of concerns and the
impact on people and populations may
lead Congress to take an additional look. In the meantime I think it’s
important for work to continue to be done so that we
have data to work with. And I think the public
does need to understand that there is a different
regulatory framework for dietary supplements. And the assumption that many
have that they are subject to a level of scrutiny, and also, there’s a
lot of belief that, they’re sold in health stores; They must be good for you. So it is something that
has been an important issue for the FDA over many years. It’s an area that has
been quite controversial because there are many
people who feel very strongly that the level of oversight
of dietary supplements as it stands is enough,
or maybe even too much. So it fits into what
I was talking about that the world looks
different for different people. But I think that it is
certainly of concern.>>Thank you.>>Hi. My name is Matt Carter. I’m EIS 1983. I’ve worked for a state health
department for over 30 years. My question is, as you know,
there are many epidemiologists in training in this room. It may not be a surprise
to you to hear that there’s been a number
of times in my career that I’ve been told that epidemiologists should do
the science and turn the science over to the policy makers. And I wonder if you have
a perspective on the role of epidemiologists
as policy makers?>>Well I think, you
know, that it’s very hard to completely tease
out and do the science and the policy in isolation. I’m a great believer that
good policy is informed by the science and
by the scientists who understand that science. And you can’t just pass a
study off that’s been published to a quote/unquote “policy
maker” and expect them to really understand how to put
it in context, how to assess it in terms of the adequacy of that
science for the problem at hand. And also to understand the
context for implementation. So I think that, you know, as you’re doing science
you’re inevitably touching on issues of policy. I think it is important,
and I suspect everyone in their EIS placements have
already been exposed to the fact that much of the scientific
and epidemiologic work is intermittently intertwined
with it’s policy implications. So, you know, I think
they go hand-in-hand. I think the critical thing is
I do not like to see policy that isn’t informed by science
and the data that’s available.>>Thank you.>>David Bell, Division of
Viral Diseases, EIS 1979. First of all, thank you for
such a magnificent talk, so inspiring, touched on so
many topics insightfully, articulately, concisely,
it was just magnificent. My question is a more
general question of Konrad’s. How do you respond to
people who believe sincerely that it should not be,
that FDA should not be able to deny approval
to products based on failure to show efficacy? Safety, they might
well agree with. But the idea that a
product should be prohibited because some expert committee or somebody didn’t
think it was effective. Maybe that should be an
advisory opinion or something? Even these dietary supplements
they do say something like not evaluated by
FDA in minute print. I agree with you people
don’t quite get that. But there are genuine
consumers who really just think that should be advisory, and how do you address? I’m not talking about insurance companies
who won’t pay for them. I’m talking about the average
person who wants to be able to buy a drug or if a
physician orders something.>>I mean it’s a
huge, huge issue, and it certainly is part
of the debate today. You know, there are proposals that FDA should only do
the initial safety studies and then move the product
into the marketplace and let the marketplace
determine whether it actually works. And people should be
informed of the risks. And if they’re willing
to take them, you know, it’s their choice. You know, I do think that
history shows that the role of a regulatory agency like FDA
in assessing safety and efficacy and quality if the
product really matters that if individuals are
willing to take on risks of an unapproved drug or a
drug where the efficacy hasn’t yet been proved, there are
some mechanisms to get access to “compassionate use”
kinds of opportunities. But to move a drug
into the marketplace without really understanding
the risks and benefits to patients has caused
great harm over many years. And the public doesn’t, you
know, you say we’ll take on the risk and if it doesn’t
work and we’re willing to pay. But still, it’s not the case, I’m trying to avoid
sounding patronizing, which is what the FDA
is always accused of. But it is very hard to
actually as an individual or the healthcare provider
make many of these assessments. And you can imagine in
individual cases it’s easy to say okay, the drug may not
provide any measurable benefit, but there are no
other treatments, and it can’t do harm. But if you introduce that
as the standard of practice across the board, you know,
I think you’re opening it up to snake oil salesmen to
harmful products to an era that we know, in fact, not only
didn’t produce health benefits for patients, but also didn’t
encourage scientific advance and innovation. It was really when the FDA was
given new authorities, a little over 50 years ago to actually
have an efficacy standard and a safety standard, that
you saw critical research advance dramatically. You saw the pharmaceutical
industry adopting new standards and practices. And in fact, you saw the
pharmaceutical industry becoming the most admired industry in
the world in the United States because of the standards
and authorities, not most admired in terms of
how they always do business, but I mean the level of quality, the ability to produce
innovative drugs, and the ability to
actually produce things that make a difference
for patients, you know, really did
change dramatically. But it’s not an easy
question to answer because if you’re the
patient with no other options, or the parent of a patient
with no other option, and the drug might help
even if it’s unproven, or you’re in the midst of a
crisis and there’s something. But a drug without proven
benefits isn’t always better than nothing. And you know, you
also see instances where patients don’t
get other treatments that would have benefits,
or harms that weren’t initially
recognized, emerge with broader use.>>Peggy, thanks for a
wonderful presentation.>>I saw you cut
the line there by the way.>>Yeah I know. [laughter] When I got this job Peggy
asked me, are you going to still do the things
I tell you to do? And I thought to
myself, did I ever? But.>>Yeah.>>I actually wanted to follow
on that question one thing, to think a little bit more
philosophically about data, picking up on some of
your comments on science, implementation science, and
the knowledge that’s out there with things like
post-marketing data. We see this issue
commonly in public health where we can see sometimes
an inappropriate deification of the RCT, even where it’s not
the most appropriate methodology for a specific question. And on the other hand, with
rare diseases, for example, the possibility if you could
get actual granular information on what was done to individual
patients you might come up with a reasonable way forward
that would be an appropriate way if we had a collaborative way of getting standardized
information monitored. So the question really is, how
can we think about the standards of evidence and types of
data collection in a way that will advance both the
regulatory approach and clinical and epidemiological care? Not easy. I think a clear
challenge, and yet something that we don’t often
explicitly address. But we think of the errors that
we’ve seen with, for example, estrogens and use of
ecological data that led to an inappropriate
recommendation, but we missed the number of
questions we’re not answering because we’re not looking
at some of the data that might be there
for the analysis.>>Yeah, well I think this
is a time of really thinking in new ways about data and much
less rigidly than we used to, and that doesn’t mean stepping
away from scientific rigor, but it means applying
science to different kinds of data and in new ways. Certainly at the FDA, you know, there’s been a very big push
towards a much more innovative set of clinical trial
designs, much more use of observational data,
historical controls, epidemiologic data, of course
has always been an important part, especially
on the safety side. But, and as electronic health
records and other kinds of databases become available,
also thinking about how to use those in new ways. It’s surprising to me how
many people actually believe, even sometimes CEOs of
pharma and biotech companies, that FDA will not approve a
drug unless there are two RCTs. You know, that is just
simply not the case, but the RCT did develop as, you
know, the gold standard for how to ask and answer
certain questions. But the truth is that the
realities of the world and also advances in understanding enable much
more flexible approaches, and much more emphasis
is now being put on adaptive clinical trial
designs and Bayesian statistics on how to more effectively
use existing databases, either with meta-analyses
or data mining to ask and answer additional questions
to better utilize existing data. And people are thinking
very hard about how to push certain kinds of
clinical trials out much closer to where the patients are
because of the opportunities that electronic health
records can offer. I mean one of the problems
is you start to think about this broader universe of
data and ways of doing things is that the rigor of the initial
data collection becomes even more important, something
that I think all of you in this room probably
understanding profoundly that, you know, if electronic health
records are reflecting very different ways of defining
cases and tracking information, then when you put
it all together to ask really important
questions, it’s actually not going to give
you the answers that you need. But I think this is a time of
great ferment and opportunity in this realm and where people
trained in data science, such as so many of you in
the EIS program, can really help with
new thinking. And, certainly
(I see Anne sitting here) thinking about
vaccine trial designs during the Ebola outbreak, It was hardly as
though, you know, the FDA had the only
perspective and scientific and real world experience to
bring to bear on what kinds of studies could
and should be done to help advance critical
scientific questions so that, in fact, important
actions could be taken if the data supported the use. [ Applause ]

Leave a Reply

Your email address will not be published. Required fields are marked *