Dr. Sharpless's remarks at the NIH Tobacco Regulatory Science Meeting October 21, 2019

Speech | In Person

• Speech by: Norman E. "Ned" Sharpless, MD ; Acting Commissioner of Food and Drugs - Food and Drug Administration

Thank you, Francis [Collins].

It is great to be back at NIH, talking about a topic of almost unmatched importance to the public health: tobacco regulatory science.

As this group is well aware, tobacco research has a history of both challenges and opportunities relating to the advancement of public health.

But I firmly believe we are at a crucial point on this timeline, and the time is now to really make a difference in this area.

Certainly, the opportunity to have an impact in shaping FDA’s work in the area of tobacco policy was an incentive for me when I was presented with the opportunity to serve as the FDA’s Acting Commissioner.

A major focus of my career has been researching and treating cancer, and mitigating the risk factors associated with the disease. 

And when you talk about cancer death and suffering in the U.S., you have to talk about tobacco.

Despite decades of efforts at tobacco control, cigarettes remain the largest preventable cause of cancer in the US. 

Lung cancer, bladder cancer, head and neck cancer, pancreatic cancer, on and on. 

And that does not even begin to mention the role of cigarettes in common, deadly non-malignant conditions like emphysema and coronary artery disease.

So, since I have spent virtually my entire professional life trying to reduce cancer suffering, I welcomed the chance to play a more direct role in helping spur development of the science, research, and regulation of tobacco products.

And one thing working at FDA has taught me is how much we need the work of you people do.  I mean we really need it.

There are so many things the FDA can do, or would like to do, or thinks it should do, but at the end of the day, the FDA has to be driven in its policy making by science and data.

And I can’t tell you how many times, since coming to the FDA, I have been asked to make a regulatory decision, and I have thought “I wish we had better data to tell us what to do here”.

And it seems to me that this has been especially true for decisions related to the FDA’s regulation of tobacco products.

Like many in this room, I have first-hand, patient-level experience with the devastating public health impact of tobacco products.

As an oncologist, I’ve cared for many patients with disease caused by cigarettes.

I vividly recall my very first ever real patient I ever treated as a medical student.

The patient had been admitted to the oncology ward with SVC syndrome; a not uncommon presentation of lung cancer, from which he was dying.

And I recall feeling how unfair it was. 

Here was this middle-aged guy, a great guy, a farmer from eastern N.C., a hard-working fellow who had agreed to let a newbie med student learn by practicing on him. 

I recall asking him if he smoked, and he said “two packs a day all my life”

And for me, the key thing to know about this devastating cancer, is that this disease was virtually unknown prior to the wide availability of cigarettes into American life.

Alton Ochsner, a venerated surgeon who founded the Ochsner clinic in Los Angeles, describes how, in 1919, while a medical student at Washington University, his attending doctor told him to attend an autopsy of someone who had recently died of metastatic lung cancer.

He was told to study this case, since this disease was so rare he’d probably never see another case. 

And he notes that he didn’t see another case for 17 years, until an epidemic ensued; just about 20 years after lots of young men began to take up smoking cigarettes with the start of WWI. 

Today, tobacco-associated lung cancer in the United States kills more Americans than breast, prostate and colon cancer combined. 

Later in my career, the research lab I ran at the Lineberger Cancer Center invented a new type of therapy being developed today for use in patients with small cell lung cancer.

And as NCI Director, I learned a lot about the funding of tobacco control research, and I was a strong proponent of NCI activities in this area, including our work with the FDA on the Tobacco Centers of Regulatory Sciences (TCORS) program.

And this path has led me to where I am now, helping to lead the FDA through a key moment in tobacco regulation, as we are confronted with an almost unbelievably dynamic landscape today.

The Family Smoking Prevention and Tobacco Control Act became law in 2009, but that effort was decades in the making. 

It took years of research and study to get to that point, representing new phase in tobacco control. 

It set the stage for a foundation of scientific research that would be essential to support the regulation of tobacco products.  

Since then, the FDA has taken many actions and, I would argue, made enormous strides in reducing the public health burden caused by tobacco. 

But no doubt, we still have a long road ahead of us.

Cigarette use among both youth and adults is at an all-time low, but more than 30 million Americans still smoke, resulting in more than 480,000 preventable deaths per year.

Which brings me to the focus of this meeting and the topic of my discussion -- the essential research you conduct to build the tobacco regulatory science base that allows FDA to decide the best course of action to protect the public health.

This research enabled landmark actions by the FDA like the 2016 Deeming Rule, which brought e-cigarettes and other products under the TCA.

It also supported our longstanding work on cigarette health warnings.

It also provides the data that are used for making product application decisions.  “Following the science” is a recurring FDA mantra in this regard.

That research is especially important right now, as we need rigorous and reliable data more than ever, to inform our knowledge of the rapidly evolving tobacco marketplace, including developments relating to products like e-cigarettes.

As I said earlier, our jobs as regulators would not be possible without the information provided by the work of tobacco regulatory scientists and researchers like those of you here today. 

For example, through the vital work of the nine Tobacco Centers of Regulatory Science nationwide, we are able to fortify our knowledge base in a variety of areas affecting tobacco regulatory science.

In addition to ongoing research, through the second phase of the TCORS program we have been able to launch a new rapid response program that allows for the exploration of novel, time-sensitive research questions.

The research produced out of this collaboration supports the acquisition of critical knowledge in areas such as chemistry, toxicology, behavior and addiction, marketing and the potential impact of FDA’s regulatory actions.

It’s led to essential research on a variety of topics across the tobacco science spectrum, including, but not limited to:
     *  Studies of the chemical constituents of e-cigarette aerosols;
     *  The toxicological impact of nicotine and flavors across different routes of exposure,
     *  The differences in tobacco use patterns with low nicotine cigarettes as compared with other tobacco products;

As I mentioned, one of the most critical areas we’re currently studying and considering research on is the growing world of novel forms of nicotine delivery. 

We need to better understand, for instance, whether these new delivery vehicles can meet the requirements to be marketed as drugs to help smokers quit, such as nicotine replacement therapy, or potentially as less harmful tobacco products for those adults who still seek to use nicotine.

For that reason, it’s vital that we continue to build our broader knowledge base about the public health impacts of products like e-cigarettes that may be evaluated for sale in either fashion.

To this end, we are supporting and encouraging work in this area.

We recently issued new guidances to encourage the development and study of both new nicotine replacement therapy products and tobacco products, including modified risk tobacco products. 

We also have established a cross-center group to engage with academic researchers and industry looking to study how products such as e-cigarettes may impact the health of currently addicted adult smokers, as well as their use of combustible cigarettes;

And we have funded a number of projects to answer these types of questions.

Another key area of research relates to flavored tobacco products, including e-cigarettes. 

Studies show that these are particularly appealing to youth and are often cited as a reason for youth initiation.

Research into elements of tobacco products, like flavors, and how they affect different populations’ intentions to use tobacco products and overall use patterns, has become a crucial component of our regulatory decisions.

As an agency, we rely on the important work TRSP scientists are doing to build our knowledge base around flavors in tobacco products and other areas of tobacco science where there are knowledge gaps.

For example, our upcoming compliance policy relating to flavors, which CTP Director Mitch Zeller will touch on a bit more in his remarks, is strongly based on the research around flavors and their appeal to youth.

Before I move on, I want to briefly mention two important FDA supported studies that offer you critical resources in your research.

The first of these is the Population Assessment of Tobacco and Health, or PATH Study, which allows scientists to study patterns of use and addiction as well as biomarkers from linked samples to help determine why people start and continue (or discontinue) tobacco use, and how their levels of use affect their health.

We launched this large longitudinal study of tobacco use patterns with the NIH in 2011, and this study has been going strong ever since.

The other study is the National Youth Tobacco Survey (NYTS), which CDC and FDA began in 2011.

This study, as I am sure you have seen, has been very much in the news of late.  

This survey tracks the use of tobacco products among U.S. middle and high school students – including which tobacco products they are most commonly using, how often they are using them, and which flavors they are using.

Data from the NYTS and other sources have shown that since 2014, e-cigarettes have become the most used tobacco product among kids.

And since 2017, we have seen a steady rise in youth use of e-cigarettes, reaching epidemic proportions last year.

Preliminary 2019 NYTS data show that this trend is not reversing.

More than a quarter of high school students reported using e-cigarettes in the past-30 days in the 2019 survey, with the majority users using non-tobacco flavors.

The trends documented by the NYTS have been alarming and have galvanized the FDA into action.

I encourage all of you to take advantage of these two valuable data sets in your work. 

Now I’d like to switch gears a bit and take a few minutes to talk about some of the specifics of the FDA’s review process as it relates to your research on tobacco products. 

When I was NCI Director, I used to complain that we were not funding specific types of studies, particularly comparisons of e-cigarette use in addicted adult smokers, as well as human studies of other novel tobacco products.

And I asked many people in the tobacco control community and at NIH, some of you here today in fact, why we were not doing more of these trials.  I was repeatedly told that the FDA regulatory structure was the problem.

Specifically, I was told this sort of trial would require an Investigational New Drug or IND, and what academic has the time, money and bureaucratic wherewithal to file one of those.

Now, since becoming Acting Commissioner at FDA, as you might imagine, I have had some opportunity to look into this issue.

And I have come to believe that there are some misunderstandings, that even persist today, about FDA’s regulatory structure for tobacco research. 

This area of research is essential to FDA, providing important evidence for our future decision-making, and we want to see these types of studies done. 

And I wanted to make sure this area of confusion is resolved.

As I hope you all know, there are multiple pathways for studies done on tobacco products, some of which may not even require interaction with the FDA.  

Here is a slide showing the relevant features of a drug versus a tobacco product trial.

If it is a drug, a product that is intended for disease mitigation or treatment including the treatment of nicotine addiction, for example, smoking “cessation,” it needs to be studied under an Investigational New Drug process (IND).

That’s probably familiar territory to most of you.

I think less well known, however, is that there is another option for human studies of novel tobacco products, and that is, an Investigational Tobacco Product or ITP.

The goal of an IND is to support a new drug application, the goal of an ITP is to support a tobacco product application. 

These products have different regulatory structures and must meet different standards.

A key thing to understand about an ITP is that it may be considerably less onerous to prepare for an academic researcher than an IND, but it still can be used for many very valuable types of studies.

Our goal at FDA is to help the research community understand which pathway is appropriate for your studies.

To clarify these two pathways a bit more: there may be similar measures used in both ITP and IND studies, for example, addiction measures, appeal, liking, and other areas.

Nicotine replacement therapies, as drug trials under IND, often measure smoking cessation, withdrawal symptoms, and craving.

These sorts of “drug claims” can be measured in an ITP study too, but they have to be secondary or tertiary outcome measures.

The primary outcome measure of an ITP trial cannot be a medical outcome, but can still be one of many outcome measures, for instance, relating to reduced harm or risk of the product.

To give you one important example, academic researchers can study a question such as how access to e-cigarettes affects use of combustible cigarettes by currently addicted adult smokers under an ITP. No IND is needed for this!

In some cases even, the FDA can waive the need for an IND or an ITP altogether, and just provide the researcher with a letter for use when their trial goes to the IRB.

But let me be really clear here, these topics are confusing and the details matter.

If you have questions about how to do your human studies with a nicotine or tobacco product, contact the FDA, specifically the Center for Tobacco Products, for advice early and often.

We look to your research findings for several key things, including to help evaluate:

     *  potential product standards;
     *  whether the marketing of a product would be appropriate for the protection of public health; and
     *  whether a product meets the standard for authorization as a modified risk product, such as whether it will significantly reduce harm and the risk of tobacco-related disease.  
 
I want to briefly mention the modified risk tobacco product application or MRTP, which is for a product that a manufacturer would like to market as reducing risk or reducing harm.

Though this may be less specifically relevant for the research being done by many of you, I mention it because your research may very likely inform the FDA’s evaluation of a product trying to make an MRTP claim. 

The MRTP pathway allows companies to submit applications to FDA for evaluation as to whether a tobacco product may be sold or distributed for use to reduce harm or the risk of tobacco-related disease.

Our reviewers generally must look at whether the applicant has demonstrated that the product – as actually used by consumers – will significantly reduce harm and the risk of tobacco-related disease to individual tobacco users and benefit the health of the population as a whole.

This includes taking into account both users of tobacco products and persons who do not currently use tobacco products.

In making this assessment, the agency must consider whether those who do not use tobacco products, for example children, would start using the product and whether existing tobacco users, who would have otherwise quit, would switch to the modified risk product instead.

If, after reviewing the evidence, we find the data convincing, we can support the company’s modified risk application.

This action does not mean these products are safe or “FDA approved,” just that they can market an MRTP claim.

But MRTP claims are not granted permanently, and if new information should lead FDA to determine that the product no longer is of public health benefit, then the agency could withdraw this authorization.

I predict MRTP claims will become very important in the near future.

And I think it should be obvious to everyone in this room how dispassionate research carried out by top-notch academics will be used by FDA to help to make determinations related to things like individual and public good of a new tobacco product seeking an MRTP claim.

Since I’ve mentioned e-cigarettes several times today, I thought I might close today with a quick update of the ongoing investigation of the e-cigarette related respiratory illnesses.

As Dr. Collins mentioned, FDA has been actively working with CDC and other federal and state partners in this investigation. 

To date, 1,479 lung injury cases associated with vaping have been reported to CDC from 49 states and territories, which tragically have resulted in 33 confirmed deaths.

At this time, FDA and CDC have not identified the cause or causes of the lung injuries in these cases and the only commonality between all cases is that patients report the use of vaping products, including e-cigarettes.

No one compound or ingredient has emerged as the cause of these illnesses to date and it may be that there is more than one cause of this outbreak.

We do know that most cases admit to using THC products, and that THC is present in most (like 80%) of the samples associated with cases and tested by the FDA to date.

As such, we recommend that no one use vaping products that contain THC, esp. ones that are black market, modified etc.

Furthermore, there is no safe tobacco product. All tobacco products, including e-cigarettes, carry a risk.

And since some cases report only using nicotine products (ie no THC), we believe the only way to be certain to avoid this type of lung injury is to not use any vaping or e-cig product.

We are working round the clock with the CDC, DEA and state and local officials to understand more about the specific causes of these illnesses and their relationship to use of vaping products.

As we know more, we will update the public.

I’ll close the way I began, by noting that it is a challenging and fascinating time to be working in the tobacco regulatory science field. 

At the FDA we are continuously working to ensure that decisions made from a tobacco regulatory standpoint are in the best interest of the health of all Americans.

And we need your research to help guide us in that mission.

I want to thank you again for being here and for your work to advance tobacco regulatory science and your role in understanding tobacco and its effects on public health.

I’d like to now hand the microphone over to Mitch Zeller, the Director of FDA’s Center for Tobacco Products.

Thank you again for inviting me to speak today, and I know this will be a good and productive conference.