FOOD AND DRUG ADMINISTRATION












                        Thursday, April 22, 2004


                               8:00 a.m.




             Advisors and Consultants Staff Conference Room

                           5630 Fishers Lane

                          Rockville, Maryland





         Kenneth I. Shine, M.D., Chair

         Jan. N. Johannessen, Ph.D., Executive Secretary




         Gail H. Cassell, Ph.D.

         Josephine Grima, Ph.D., Consumer Representative

         Susan Harlander, Ph.D.

         Cato T. Laurencin, M.D., Ph.D.

         Cecil B. Pickett, Ph.D.

         F. Xavier Pi-Sunyer, M.D., M.P.H.

         Jose C. Principe, Ph.D.

         Jim E. Riviere, D.V.M., Ph.D.

         Allen D. Roses, M.D.

         Katherine M.J. Swanson, Ph.D.

         John L. Thomas, Ph.D.




         Lester M. Crawford, D.V.M., Ph.D.,

         Norris E. Alderson, Ph.D.




         Daniel A. Casciano, Ph.D.

         David W. Feigel, Jr., M.D., M.P.H.

         Kathy Carbone, M.D.

         John Marzilli

         Robert E. Brackett, Ph.D.

         Steven Galson, M.D., M.P.H.



                            C O N T E N T S


      Call to Order, Kenneth I. Shine, M.D., Chair,              5


      Welcome and Opening Remarks,

        Lester M. Crawford, D.V.M., Ph.D., Acting

          Commissioner of Food and Drugs                         9


      Overview of the FDA Initiative on Obesity,

        Robert E. Brackett, Ph.D., CFSAN, FDA                   19


      Obesity - Therapeutics, David G. Orloff, M.D.,

        CDER, FDA                                               27


      Obesity - Research, David W.K. Acheson, M.D.,

        CFSAN, FDA                                              47


      Highlights of the Obesity Working Group Report,

        Alan Rulis, Ph.D., CFSAN, FDA                           76


      Questions and Discussion with the

        Board/Presenters                                        96


      Update on ORA Peer Review Process,

        John R. Marzilli, Deputy Associate

        Commissioner for Regulatory Affairs, FDA               129


        John J. Specchio, Ph.D., ORA Science Advisor           135


      Open Public Hearing:


        Arthur Frank, M.D., George Washington University       150

        Elizabeth Jacobson, Ph.D., AdvaMed                     158

        Richard Atkinson, M.D., American

          Obesity Association                                  170


      Introduction to Critical Path, Janet Woodcock,

        M.D., Acting Deputy Commissioner for

        Operations, FDA                                        175


      Perspective on Anti-Infectives and Vaccines,

        Gail H. Cassell, Ph.D., Eli Lilly and Company          220


      Perspective on Chronic Disease Therapies,

        Robert M. Califf, M.D., Duke University                241



                            C O N T E N T S


      Drug Formulation and Development, and Tissue

        Engineering Issues, Robert S. Langer, Sc.D., MIT       268


      Overview of Opportunities - Drugs, Robert Temple,

        M.D., CDER, FDA                                        298


      Overview of Opportunities - Devices, Larry G.

        Kessler, Sc.D., CDRH, FDA                              324


      Overview of Opportunities - Biologics,

        Jesse Goodman, M.D., M.P.H., CBER, FDA                 339


      Questions and Discussion with Board -

        Recommendations                                        363




  1                      P R O C E E D I N G S


  2                          Call to Order


  3             DR. SHINE:  Good morning, ladies and


  4   gentlemen.  We will come to order.  Welcome to this


  5   meeting of the FDA Science Board Advisory


  6   Committee.  I am Ken Shine.  Mark McClellan, when


  7   he was Commissioner, asked me if I would chair this


  8   committee then he split!


  9             [Laughter]


 10             I was a little anxious because our


 11   colleague, Dr. Crawford, who is the Acting


 12   Commissioner, was scheduled perhaps to be in Japan


 13   but it turns out that he is able to be here so I


 14   don't feel quite so deserted.  But we are pleased


 15   to be able to welcome you to this meeting which


 16   will be focused on two major and extremely


 17   important issues for all of us, the issues relating


 18   to the epidemic of obesity, which is a worldwide


 19   epidemic of extraordinary proportions in terms of


 20   all of the implications of that epidemic; and then


 21   an examination of the Critical Path in terms of the


 22   necessity to find ways to bring new products to




  1   market in a timely and cost effective way.


  2             We have a very distinguished advisory


  3   committee and before we ask Dr. Crawford to make


  4   his introductory comments, perhaps we could go


  5   around, starting with Dr. Pickett, and ask you to


  6   identify yourself and then just a sentence or so


  7   about your area of interest or perspective that you


  8   bring to the committee so that folks have a sense


  9   of your approach to things.  Dr. Pickett?


 10             DR. PICKETT:  Yes, good morning.  I am


 11   Cecil Pickett.  I am President of Research and


 12   Development for the Schering-Plough Corporation,


 13   which is the pharmaceutical arm of Schering-Plough.


 14   I obviously have a fundamental interest in drug


 15   discovery and drug development and how we can bring


 16   innovative new therapies to patients.


 17             DR. PRINCIPE:  Good morning.  My name is


 18   Jose Principe.  I am Distinguished Professor of


 19   Electrical and Biomedical Engineering at the


 20   University of Florida, and my expertise resides in


 21   electrical systems and machine and learning


 22   algorithms.




  1             DR. RIVIERE:  Hello.  I am Jim Riviere.  I


  2   am Distinguished Professor of Pharmacology, North


  3   Carolina State University, and have expertise in


  4   pharmacology and toxicology.


  5             DR. GRIMA:  Hi. My name is Josephine


  6   Grima.  I am the Director of Research and


  7   Legislative Affairs for the National Marfan


  8   Foundation, and I am the consumer representative.


  9             DR. THOMAS:  Good morning.  I am John


 10   Thomas, Vice President, retired, and Professor


 11   Emeritus of Pharmacology and Toxicology, University


 12   of Texas Health Science Center at San Antonio.


 13             DR. SWANSON:  Good morning.  I am Katie


 14   Swanson.  I am with the President of KMJ Swanson


 15   Food Safety, a food safety consulting firm.


 16             DR. LAURENCIN:  I am Cato Laurencin.  I am


 17   a Lillian Pratt Distinguished Professor and Chair


 18   of Orthopaedic Surgery, and university professor at


 19   the University of Virginia.  My areas of expertise


 20   are biomaterials, tissue engineering and


 21   nanotechnology.


 22             DR. PI-SUNYER:  I am Xavier Pi-Sunyer.  I




  1   am Professor of Medicine at Columbia University


  2   College of Physicians and Surgeons, and I am


  3   Director of the Division of Endocrinology and the


  4   Obesity Research Center at St. Lukes Roosevelt


  5   Hospital.  My area of interest is diabetes and


  6   obesity.


  7             DR. HARLANDER:  Hello.  My name is Susan


  8   Harlander.  I am president of my consulting firm,


  9   called BIOrational Consultants.  My background is


 10   in food science and nutrition and I work primarily


 11   in the areas of genetically modified foods and


 12   drugs.


 13             DR. ROSES:  I am Allen Roses.  I am Senior


 14   Vice President in Genetics Research,


 15   GlaxoSmithKline.  I spent 27 years at Duke and the


 16   final 20 of those I was Chairman of Neurology.  My


 17   expertise is in neurology and genetics, medicine


 18   and a variety of other.


 19             DR. SHINE:  Thank you.  Have I missed


 20   anybody on the committee?  We will be hearing from


 21   some of our colleagues at the FDA shortly.  I am


 22   Ken Shine.  I serve currently as the Executive Vice




  1   Chancellor of Health Affairs at the University of


  2   Texas System, after two terms at the Institute of


  3   Medicine.  I am interested in health policy.  As a


  4   cardiologist, I also recommend the food for


  5   breakfast--


  6             [Laughter]


  7             --and hope that in the interest of


  8   controlling obesity we will all have heart healthy


  9   lunches.  So, we will see!


 10             I think we are very fortunate that Les


 11   Crawford can serve as the interim Commissioner.  I


 12   have known Dr. Crawford for many years and his


 13   leadership in this organization has been manifest


 14   over and over again.  He brings wonderful


 15   experience and perspective and we will ask him to


 16   make a few remarks.  Les?


 17                   Welcome and Opening Remarks


 18             DR. CRAWFORD:  Well, thanks very much, Dr.


 19   Shine, and thank you very much for agreeing to be


 20   chairman.  It is one of the lasting legacies of the


 21   great Mark McClellan that you are here.  You cannot


 22   be replaced until he comes back--




  1             [Laughter]


  2             --it is almost like a biblical thing.


  3             DR. SHINE:  Now I am worried!


  4             DR. CRAWFORD:  In any case, I want to


  5   welcome you as the chairman and also we have four


  6   new members, all of whom I have known before except


  7   Dr. Allen Roses, and I am particularly grateful for


  8   you to agree to serve on this committee.  We expect


  9   great things from you and you will have a fun time.


 10   I think your particular area of expertise is very


 11   much needed by the committee and I hope it is an


 12   enjoyable and fruitful thing for you.


 13             I have known Dr. Susan Harlander for a


 14   long time, and she was been nominated for this


 15   committee and turned us down one time before but


 16   she can run but she can't hide.  She is right here


 17   today, and thank you for that.


 18             Xavier Pi-Sunyer and I served on the same


 19   committee, another committee which met only one


 20   day, Dr. Pi-Sunyer, and went away, some ten years


 21   ago.  This one is enduring.  So, thank you also.


 22             Gail Cassell--I think Gail is not here yet




  1   but she is coming.  Also, she is very well


  2   recommended because she comes from the University


  3   of Alabama, Birmingham.  She and I speak the same


  4   language and communicate often.  So, we are


  5   grateful to her also.


  6             We have had, as I mentioned earlier, the


  7   transfer actually of Mark McClellan to the Center


  8   for Medicare and Medicaid Services.  That is a blow


  9   for us but it is a strengthening of our Department


 10   of Health and Human Services, which is our umbrella


 11   organization under Tommy Thompson.  So, Dr.


 12   McClellan is still available to us and we see him


 13   fleetingly but he is very much interested in what


 14   is happening here, and we will continue to stay in


 15   touch throughout this administration and beyond.


 16             We remain focused on his strategic plan


 17   that has now become our strategic plan and also on


 18   the five goals where were developed during that


 19   time, which were shared and worked out to some


 20   extent in concert with this committee.  Those have


 21   stood the test of time.  All the work is not


 22   completed but we believe those benchmarks that were




  1   established by the committee or commission on the


  2   strategic plan which meets monthly in order to do a


  3   check of how well we are doing--we think all of


  4   that work will be accomplished within this


  5   presidential administration.  At that time we will


  6   put a ribbon around it, put it in a box and serve


  7   it up to the American people.  I think it is a job


  8   already well done but a job not quite completed.


  9             We are focusing on our mission of


 10   protecting and advancing public health.  We face


 11   many new challenges and opportunities.  We are


 12   proceeding with your help through the most


 13   difficult part, which is bringing science to bear


 14   on the regulatory process.


 15             This session of the FDA Science Advisory


 16   Board is scheduled, actually, at a very opportune


 17   time.  The agency has undertaken a number of major


 18   new initiatives, two of which you will be hearing


 19   about in much greater detail during the remainder


 20   of the day.


 21             On March 12 of last year Secretary


 22   Thompson released a new FDA report outlining the




  1   agency's strategy for combating the major public


  2   health problem of obesity, actually initiated it on


  3   March 12 of last year and received a report from


  4   FDA this year.  In point of fact, three different


  5   agencies, under the leadership of Secretary


  6   Thompson, did major initiatives on obesity.  These


  7   were six-month programs to bring together the


  8   expertise in the National Institutes of Health, the


  9   Centers for Disease Control and the Food and Drug


 10   Administration.


 11             During the time that those three


 12   committees were working on the problem of obesity,


 13   from its very fundamental scientific rationale all


 14   the way up to ameliorative steps, the estimated


 15   number of deaths from obesity-related diseases in


 16   the United States increased from 300,000 per year


 17   to 400,000 per year.  A major path-breaking paper


 18   by Dr. Julie Gerberding and others at the Centers


 19   for Disease Control and Prevention have estimated


 20   that obesity is going to overtake smoking as the


 21   leading cause of death in the United States by the


 22   end of this decade.




  1             These are chilling figures.  It is a


  2   horrible disease, a complex of diseases that is


  3   lurching out of control.  FDA, through the


  4   authorities it has under the Nutrition, Labeling


  5   and Education Act, must do something.  Dr. Bob


  6   Brackett is going to detail that for you.  He came


  7   in as Director of the Center for Food Safety and


  8   Applied Nutrition in the middle of the obesity


  9   initiative but his expertise and leadership are


 10   very much part and parcel of our accomplishing of


 11   this mission.  He will talk about the other people


 12   from his Center and elsewhere who were on the


 13   committee, but it is a great accomplishment for FDA


 14   and I am very pleased that you are going to hear


 15   about it in depth from Dr. Brackett himself.


 16             The second major thing is the Critical


 17   Path initiative which was developed in the last


 18   stages of Dr. McClellan's tenure here.  It has


 19   stood the test of introduction; it has not stood


 20   the test of time yet.  But with your help we will


 21   get the Critical Path from the research laboratory


 22   to the bedside, to the pharmacy, to the hospital




  1   and all other places where we need to be sure that


  2   FDA is not an impediment to the development and


  3   introduction of new drugs and other modalities of


  4   therapy, and also fine-tuning our procedures so


  5   that we actually encourage by efficiency the


  6   development of much needed drugs in much needed


  7   areas.


  8             One of the things that you will hear about


  9   today is a publication, on a regular basis, of


 10   Critical Path opportunities that we will list to


 11   the public, to the industry that we serve, and also


 12   to all other stakeholders about what we think are


 13   the opportunities for new development that FDA


 14   would like to work with sponsors on, work with


 15   research institutions on and anybody and everybody


 16   else.  This is something new for FDA and I think we


 17   are ready for it, but you will also have some


 18   targets of opportunity this morning to help shape


 19   and develop that critical initiative.  I believe it


 20   will be with us for a long time.  We have had some


 21   similar kinds of things in the past that we have


 22   come up with, but this one has a system to it and




  1   we believe, if we do it right, it will be enduring


  2   and it will mark a new era for the Food and Drug


  3   Administration.  So, your critical attendance to


  4   that is very much solicited.  Dr. Woodcock will be


  5   talking about that.


  6             At this point I would like to turn the


  7   floor back over to Ken Shine, with many thanks once


  8   again for his leadership on this committee.  I am


  9   looking forward to the day, as I hope all of you


 10   are.  Thank you.


 11             DR. SHINE:  Thank you very much, Dr.


 12   Crawford.  One of the responsibilities of this


 13   committee is to be the final judges in the FDA


 14   scientific achievement awards program.  Those


 15   awards apparently will be given in another month or


 16   so, but I think one of the parts of our activities


 17   has been the opportunity to look at the quality of


 18   the science.  I had a great deal of difficulty in


 19   choosing in many categories the more outstanding of


 20   the proposal because the science was so good.  I


 21   think that is an area that has been extremely


 22   encouraging to the committee.




  1             We do have some other business we have to


  2   undertake before we begin the program, and Jan


  3   Johannessen is going to take care of that.


  4             DR. JOHANNESSEN:  Thank you, Dr. Shine.


  5   The following announcement addresses the issue of


  6   conflict of interest with respect to this meeting,


  7   and is made part of the public record to preclude


  8   even the appearance of such at the meeting.


  9             The Food and Drug Administration has


 10   prepared general matters waivers for Drs. Shine,


 11   Principe, Pickett, Grima, Riviere, Laurencin,


 12   Swanson, Thomas, Roses, Pi-Sunyer, Cassell,


 13   Harlander and one of the guest speakers, Dr.


 14   Califf.  A copy of the waiver statements may be


 15   obtained by submitting a written request to our


 16   Freedom of Information office.  The waivers permit


 17   them to participate in the committee's discussion


 18   of FDA's obesity working group report and Critical


 19   Path initiative.


 20             Topics of today's meeting are of broad


 21   applicability and, unlike issues before a committee


 22   in which a particular product is discussed, issues




  1   of broader applicability involve many industrial


  2   sponsors and academic institutions.  The


  3   participating committee members have been screened


  4   for their financial interests as they may apply to


  5   these general topics at hand.  Because general


  6   topics impact so many institutions, it is not


  7   practical to recite all the potential conflicts of


  8   interest as they apply to each participant.  The


  9   FDA acknowledges that there may be potential


 10   conflicts of interest but, because of the general


 11   nature of the discussion before the committee,


 12   these potential conflicts are mitigated.


 13             We have open public comments scheduled for


 14   eleven o'clock.  I would just remind everyone to


 15   turn your microphones on when you speak so that the


 16   transcriber can pick everything up.  Thank you.


 17             DR. SHINE:  Thank you very much, Jan.  I


 18   think we are prepared now to go to our program.  I


 19   would just make a couple of observations.  This is


 20   a very dense program and we are going to have to,


 21   on the one hand, hold our speakers to the time that


 22   is allotted to them and, at the same time, I would




  1   urge you to make notes and recognize that if they


  2   use their full allotted time we are not going to be


  3   able to question them at that time but, rather, we


  4   have a specific period at 10:15 for a period of


  5   questions.  So, if there are issues where you


  6   really need clarification in order to understand


  7   what is being proposed, then by all means we ought


  8   to do that.  On the other hand, we are going to


  9   have to move expeditiously through the


 10   presentations if we are going to get today's work


 11   done.


 12             We are pleased that the overview for the


 13   FDA initiative on obesity, as you have heard, will


 14   be provided by Dr. Robert Brackett and we invite


 15   him to proceed.


 16            Overview of the FDA Initiative on Obesity


 17             DR. BRACKETT:  Thank you, Dr. Shine.


 18             [Slide]


 19             Good morning, everybody.  I am Bob


 20   Brackett and what I am going to do is give a very


 21   brief overview of sort of the major points of the


 22   obesity initiative, and then following me the next




  1   three speakers will actually get into some of the


  2   more final details that were part of the


  3   initiative, as well as some of the summary of the


  4   report.


  5             [Slide]


  6             I think the background for why we did this


  7   is pretty much apparent to most people in that


  8   people have sort of rediscovered that obesity in


  9   this country and worldwide is, in fact, of epidemic


 10   proportions in that in the United States overweight


 11   and obese people have increased risks of many other


 12   chronic diseases that are relating to the deaths


 13   that Dr. Crawford mentioned, including heart


 14   disease, diabetes and certain types of cancer.


 15   Also, as Dr. Crawford mentioned, it is enough so


 16   that there are significant deaths, to the point


 17   where that is competing with tobacco as a public


 18   health problem.  So, it is something that we do


 19   need to address within FDA, something that we have


 20   partnered on with other entities within Health and


 21   Human Services.  In fact, this is sort of a


 22   nationwide program where it takes the participation




  1   and the partnership of many different groups.  That


  2   is one of the things we have attempted to do and


  3   will attempt to do.


  4             [Slide]


  5             One thing that is lost, in addition to the


  6   400,000 deaths that are estimated related to


  7   obesity, is the economic cost of obesity to this


  8   country.  That is estimated at 117 billion dollars


  9   per year.  So, that has a major impact on the


 10   health costs in this country and does drive the


 11   cost for everybody.  So, it is something that we


 12   all need to participate in trying to eliminate.


 13             [Slide]


 14             The obesity working group was actually


 15   created in 2003, in August, by Dr. McClellan when


 16   he was here.  At that time Dr. Crawford was the


 17   chair and my predecessor, Joe Levitt, was the


 18   deputy chair at that time.


 19             [Slide]


 20             They were given a very simple charge, and


 21   that was to prepare a report that outlines an


 22   action plan that would cover the critical




  1   dimensions of the obesity problem that FDA could


  2   participate in with the other agencies as well.


  3             [Slide]


  4             During that time the group was very


  5   active.  From 2003 to 2004--that is not much time


  6   to do all of the activities that they had to and


  7   they were very, very active.  It was on a fast


  8   track.  The obesity working group met eight times


  9   during that short period of time.  They received


 10   briefings from a number of different invited


 11   experts from the Department of Health and Human


 12   Services, as well as and including Centers for


 13   Disease Control and NIH.  We did hold one public


 14   meeting and one workshop; two round table


 15   discussions; and also solicited from the public


 16   many different comments on our obesity related


 17   issues by docket submissions.  So, in fact, we did


 18   try to absorb as much information to put in this


 19   report as we possibly could, and then tried to


 20   synthesize all of what was provided and provide the


 21   report that was required.


 22             [Slide]




  1             This is just a copy of the report, and


  2   this has been submitted.  It is called "Calories


  3   Count" and it is the report of the working group on


  4   obesity.  What the report actually does is to


  5   provide a range of both short- and long-term


  6   recommendations to address this epidemic.


  7             An important part is that we did try to


  8   base all of these recommendations on known


  9   scientific facts.  So, it did take some teasing


 10   apart of what was thought to be contributing to


 11   obesity versus what is known from a nutritional


 12   standpoint.  The one thing it also attempted to do,


 13   and did, is address the multiple facets that


 14   contribute to the obesity problem, particularly


 15   those that are under FDA's purview.


 16             [Slide]


 17             Some of the recommendation highlights that


 18   were given from it are, first of all, developing


 19   appropriate and effective consumer messages to aid


 20   consumers in making wiser dietary choices.  That


 21   was one of the most important things, that is, to


 22   actually get consumers to understand that they are




  1   in control of their weight problems, and to


  2   establish educational strategies and partnerships


  3   to support these appropriate methods to teach


  4   people, and particularly children with regard to


  5   childhood obesity, how they can lead better lives


  6   through better nutrition.  So, this is getting back


  7   to some really fundamental issues that needed to be


  8   addressed to the American people.


  9             [Slide]


 10             It also involved pursuing improvements to


 11   the labeling of packaged foods with respect to


 12   caloric and other nutritional information, that is,


 13   giving the consumers the information they need to


 14   make the judgments that we were trying to educate


 15   them about.


 16             Then, encouraging and enlisting


 17   restaurants in voluntary, collaborative efforts to


 18   combat obesity and then also provide nutritional


 19   content information to consumers at the point of


 20   sale.  Since many of the meals are eaten away from


 21   the home, this was particularly important.


 22             [Slide]




  1             It also recommended facilitating the


  2   development of new therapeutics that could be used


  3   in the treatment of obesity, and then,


  4   coincidentally, designing and collaborating with


  5   others--and that "others" is very broad--effective


  6   research in the fight against obesity.  So, it was


  7   really trying to encompass the whole scope of


  8   activities that could be done.  Again, the


  9   important part was really involving the


 10   stakeholders continuously throughout these various


 11   processes.  We had to not be dictating what this


 12   was but it was actually a very participatory


 13   process.


 14             [Slide]


 15             The conclusions, in summary were, as many


 16   of us already know, that the problem of obesity in


 17   America really has no single cause.  There is no


 18   one thing that you could point to; it is really the


 19   result of a variety of different factors that when


 20   they act together over time--and this includes the


 21   genetic component for consumers and environmental


 22   factors--do contribute to increasing obesity and,




  1   consequently, there also is no single solution to


  2   this problem in that the current trends will only


  3   be reversed if you have well-coordinated,


  4   complementary efforts from virtually all sectors of


  5   society to combat this.


  6             [Slide]


  7             The other thing, and the part that we


  8   needed to particularly emphasize to consumers, is


  9   that the obesity epidemic is not going to be solved


 10   quickly, neither will their individual weight


 11   problems be solved quickly.  Any long-lasting


 12   reversal of the phenomenon will itself be a


 13   long-term process.  We took a long time to get to


 14   this point and it is going to take some time to


 15   reverse it.


 16             [Slide]


 17             Just to give you a little bit of update


 18   about the obesity working group, Dr. Rulis, who


 19   will be speaking this morning as well, has been


 20   engaging in a national policy dialogue of what


 21   things can and could be done with regard to


 22   obesity, especially FDA's participation.  Dr.




  1   Orloff, who will also be following up, has dealt a


  2   lot with the therapeutics aspects of obesity and,


  3   of course, the research component, which will be


  4   discussed by Dr. Acheson, can provide more details


  5   on where the research sort of would be heading in


  6   the future.


  7             With that, I will end and, again, leave


  8   some of the details to the speakers that follow,


  9   and with them you will get a lot more of the


 10   nitty-gritty of what the obesity working group has


 11   accomplished in the last year.


 12             DR. SHINE:  Thank you, Dr. Brackett.  Why


 13   don't we proceed then to hear from David G. Orloff,


 14   who is the Director of the Division of Metabolic


 15   and Endocrine Drugs in the Center for Drug


 16   Evaluation and Research, to talk about therapeutics


 17   involved in obesity?


 18                      Obesity - Therapeutics


 19             DR. ORLOFF:  Good morning.  Thank you very


 20   much.


 21             [Slide]


 22             What I am going to use my time on to do




  1   today is to give you a brief overview of what the


  2   therapeutics subgroup which largely consisted of


  3   members of the Division of Metabolic and Endocrine


  4   Drug Products--myself, Dr. Eric Colman and Dr.


  5   Patricia Beaston--reported to the overall obesity


  6   working group according to our charge from Dr.


  7   McClellan and the original charge to the group


  8   itself.


  9             Specifically, I will give you a sense and


 10   an understanding, I hope, of where we are today in


 11   our regulatory stance; how we got here; and what


 12   our plans are for the immediate future as we


 13   participate in this enterprise to address this


 14   public health problem.


 15             [Slide]


 16             Let me start with two quotes which


 17   actually are cited by Dr. Bray, who is a leader in


 18   this field, in a recent paper that is actually


 19   included in a volume edited by Dr. Pi-Sunyer who is


 20   with us.


 21             The first is that sudden death is more


 22   common in those who are naturally fat than lean. 




  1   This sounds like a contemporary summary statement


  2   from a modern epidemiologic study.


  3             The second, which is a bit older sounding


  4   but perhaps more broadly conclusive in a sense,


  5   reads that corpulency, when in an extraordinary


  6   degree, may be reckoned a disease, as it in some


  7   measure obstructs the free exercise of the animal


  8   functions, and has a tendency to shorten life by


  9   paving the way to dangerous distempers.


 10             Well, as the title of this slide suggests,


 11   these are actually not new observations.  The first


 12   is a quote from Hippocrates and the second is a


 13   quote from Dr. Fleming of the Edinborough School,


 14   writing in 1760.


 15             [Slide]


 16             Today we call these risks associated with


 17   obesity co-morbidities.  While they are certainly


 18   better enumerated and their pathophysiology better


 19   understood, as I have suggested, this is not a new


 20   problem.  As you can see and as everyone is aware


 21   around the table, these co-morbidities run the


 22   gamut from cardiovascular disease and all of its




  1   manifestations through the big problem of metabolic


  2   syndrome and burgeoning epidemic or existing


  3   epidemic of type 2 diabetes, to increased risk for


  4   a variety of malignancies and a whole host of


  5   psychological disorders, including depression and


  6   eating disorders.


  7             One of the reasons I start with this slide


  8   is because, frankly, the drug side of FDA has been,


  9   for lack of a better term, accused in the past of


 10   being somewhat insensitive to the magnitude of this


 11   problem as reflected in all of these risks, and I


 12   want to assure everyone that we fully understand


 13   the overall metabolic and health consequences of


 14   obesity and it drives our interest in ongoing


 15   active participation in this initiative.


 16             [Slide]


 17             So, with that, Dr. McClellan gave us


 18   really two charges that asked us to address the


 19   problem, we believe, from two different sides.  The


 20   first was to assess the real or perceived barriers


 21   to development of new or enhanced therapeutics.


 22   Then, as I said, coming at it from the other side,




  1   to make recommendations on ways to encourage


  2   development of new or enhanced therapeutics.


  3             We took this as a call, on the one hand,


  4   to make sure, as always, that we were well informed


  5   and up to date in our understanding of obesity and


  6   its risks, but also that we really ought to be


  7   revisiting our FDA guidance to industry on


  8   development of drugs for obesity.  Needless to say,


  9   FDA guidance to industry is supposed to represent


 10   current thinking and I think it is worth at least


 11   considering that 1996 is retreating into the past


 12   and we ought to make sure that that is still our


 13   current thinking.


 14             So, we have an open comment period on that


 15   document that is closing in a few weeks.  We have


 16   already had face-to-face dialogue with the American


 17   Obesity Association of PhRMA, of which Dr. Crawford


 18   was president, and we will be convening an advisory


 19   committee later this year to discuss potential


 20   changes to our guidance.


 21             [Slide]


 22             The harsh reality of the state of medical




  1   therapeutics is really where we start.  The fact is


  2   that although there are a number of drugs on the


  3   market for the treatment of obesity, current


  4   therapies are really not the panacea or in any way


  5   miracle drugs.  They generally induce only modest


  6   degrees of weight loss.  Weight maintenance is


  7   really a central problem in addressing this public


  8   health issue.


  9             It is important to understand, with regard


 10   to the state of the evidence, that we have limited


 11   data available on the impact of drug-associated


 12   weight loss on morbid outcomes.  The Xendos trial


 13   with Orlistat in obese patients at risk for type 2


 14   diabetes is one recent example of a finding that


 15   touches or that addresses the effects of weight


 16   loss on that significant outcome.  But we really


 17   have no mortality data and we think that that is a


 18   big hole.  I think everybody agrees that that is a


 19   big hole in our understanding.


 20             [Slide]


 21             But having said that, opportunities


 22   abound.  This is a list of the potential targets




  1   and mechanistic approaches to the treatment of


  2   obesity that are really under development and


  3   consideration and research, and the list grows


  4   daily with an increasing understanding by those


  5   involved in the scientific side of this enterprise,


  6   with increasing understanding not only of the


  7   physiology of weight maintenance and of energy


  8   economy in general, but also the pathophysiology of


  9   obesity.


 10             [Slide]


 11             Let me tell you where we see the path


 12   forward to safe and effective obesity drugs from


 13   the standpoint of the Center for Drugs.  To do so,


 14   I need to tell you a little bit about the modern


 15   history of obesity therapeutics; to talk to you


 16   about standards of evidence for approval of drugs


 17   prior to our 1996 guidance; and the transformation


 18   in medical perception of obesity to the way it is


 19   looked at today that led ultimately to the


 20   development of our standards and rationale in our


 21   1996 guidance.  There are multiple areas for


 22   discussion.  I will really touch mostly on just one




  1   of them.


  2             These, if you will, constitute some of the


  3   barriers which Dr. McClellan asked us to address,


  4   as well as a number of unanswered questions that,


  5   in our mind, constitute barriers as well, although


  6   perhaps not barriers in the same way as regulatory


  7   barriers.


  8             With regard to the modern history, as I


  9   think most people realize, it is a checkered one.


 10   It has been fraught with ill-conceived mechanistic


 11   approaches, unscrupulous investigators and


 12   practitioners and a lot of bad luck along the way,


 13   if nothing else.


 14             [Slide]


 15             It begins in the 1880s with the use of


 16   thyroid extract and drug-induced hyperthyroidism as


 17   a path to weight loss with its attendant risks,


 18   into the 1930s with dinitrophenol which,


 19   incidentally, continues to rear its head even today


 20   and which, as many of you realize, is one of the


 21   poster children in the FDA chamber of horrors that


 22   led ultimately to the passage of the 1938 Food,




  1   Drug and Cosmetic Act, along with the elixir of


  2   sulfinamide tragedy, to amphetamines which really


  3   came to market in the mid-1930s and, as I will say


  4   in a few minutes, dominated the scene with regard


  5   to obesity therapeutics over the last half century


  6   and their problems related to addiction and CNS and


  7   cardiac toxicity.


  8             The late 1960s marked really the end of


  9   the Rainbow pill problem which had begun some 20 or


 10   25 years before.  These were medical regimens which


 11   included fixed-dose combinations of digitalis and


 12   thyroid hormone but, in the collective, included


 13   the addition of thiazide and other diuretics,


 14   purgatives as well as amphetamines.  It was that


 15   lethal combination of digitalis and thiazides with


 16   hypokalemia and accentuated digitalis toxicity that


 17   led to numerous tragedies and ultimately to


 18   regulatory action against this enterprise.


 19             The 1970s saw a mini epidemic in primary


 20   pulmonary hypertension, mostly in Europe, related


 21   to Aminorex and I think people are aware of the


 22   unfortunate case of Redux and the unexpected, but




  1   in some cases, frankly malignant cardiac


  2   valvulopathy that resulted from the use of those


  3   drugs.


  4             I think it is worth pointing out, and


  5   everyone should realize, that in terms of a barrier


  6   that this history, on the one hand definitely


  7   tempers our approach from a regulatory standpoint


  8   to the development of therapeutics in this area,


  9   but I also think that it has affected in the past,


 10   and continues to affect, the overall integrity of


 11   the anti-obesity enterprise and it is something, if


 12   you will, that from a public relations standpoint


 13   needs to be dealt with.


 14             [Slide]


 15             This is a list of the centrally-acting


 16   anorexigens approved after 1938.  I put it up


 17   really to show you that the last 50 years is the


 18   half century of amphetamine congeners in obesity


 19   research and therapeutics.


 20             Two drugs on this list, mazindol and


 21   sibutramine, are not amphetamines per se but I


 22   think all these drugs are stimulant anorexigens and




  1   they have all been marketed as controlled


  2   substances.  All, except for sibutramine, as I will


  3   explain in a moment, were approved and labeled for


  4   only short-term use.


  5             [Slide]


  6             So, what were the standards of evidence


  7   that we had to support the use of these drugs prior


  8   to 1996?  As I said, all of the drugs approved


  9   prior to that time, and so labeled for treatment of


 10   obesity were for short-term use.  The trials that


 11   supported the efficacy and safety of these products


 12   were up to 12 weeks in duration and were limited in


 13   size with 200-400 patients.  There were obviously


 14   concerns about abuse and addiction potential that I


 15   mentioned a moment ago with these products and, as


 16   I said, they were labeled for short-term use,


 17   really dating back to the late 1960s and early


 18   1970s.


 19             Their efficacy was modest and, as you will


 20   see in a moment, not really all that different from


 21   what we have today, with the mean loss of


 22   approximately 5 kg for placebo and a range of




  1   placebo-subtracted means across multiple studies of


  2   1-10 kg.


  3             [Slide]


  4             Although this is an age list epidemic and


  5   the observations of its association with chronic


  6   morbid and mortal conditions, you know, goes back


  7   to the ancients, nevertheless, it took a sort of


  8   reexamination to lead to a transformation in the


  9   way this disease was perceived and in the way that


 10   it ought to be treated.  As I said, today it is


 11   looked at as a chronic condition associated with


 12   metabolic derangements and conferring the risk for


 13   long-term morbid and mortal sequelae.


 14             As I said, there is a big problem with the


 15   high rate of weight regain following


 16   discontinuation of drugs, and there is a


 17   recognition that maintenance of healthy weight is


 18   critical to reduction in risk for


 19   obesity-associated adverse outcomes as opposed to


 20   cycling of weight.


 21             [Slide]


 22             With this recognition or this casting in a




  1   metabolic light, in 1992 the obesity drugs were


  2   transferred to Endocrine and Metabolic, and in


  3   1995, before my time, an advisory committee was


  4   held to discuss this evolution and a disease model,


  5   the standards for lifelong treatment algorithms


  6   with these drugs, and discussion of clinical trial


  7   design and evidentiary standards.


  8             [Slide]


  9             In 1996 a draft guidance was issued.  The


 10   cardinal features of that draft guidance include


 11   the patient populations which are to be targeted,


 12   which include those patients who have significant


 13   obesity and who are at high risk for sequelae.


 14   This is in keeping with the NIH evidence-based


 15   treatment guidelines which were issued in that same


 16   time frame.


 17             The duration of Phase 3 trials which we


 18   have adhered to up until now include a first year


 19   of placebo-controlled investigation to provide


 20   proof or principle of efficacy, followed by an


 21   open-label year, in the second year, to provide


 22   further information on durable efficacy and safety




  1   in long-term use.  This harkens back to the


  2   historical bad luck to which I referred and,


  3   frankly, to the absence of outcomes data with


  4   existing drugs and to the fact that we are not


  5   requiring any outcomes data for establishing the


  6   balance of risk and benefit for these products.


  7             [Slide]


  8             With regard to the efficacy criteria, it


  9   is notable that the FDA's efficacy standard is less


 10   rigorous than the European one.  We require either


 11   a demonstration of a mean placebo-subtracted weight


 12   loss greater than or equal to five percent of


 13   baseline body weight, or that the proportion of


 14   subjects who lose greater than or equal to five


 15   percent of their baseline body weight is greater in


 16   the drug than the placebo group.  The EMEA, as you


 17   can see, has ten percent cutoffs for both those


 18   criteria.


 19             [Slide]


 20             Three drugs have been approved for


 21   long-term treatment under the current guidelines.


 22   The first, dexfenfluramine, was withdrawn less than




  1   18 months after its approval, as I mentioned


  2   earlier, related to unexpected cardiac


  3   valvulopathy.  Sibutramine, a centrally-acting


  4   anorexigen, and Orlistat, a non-absorbed intestinal


  5   lipase inhibitor, remain on the market.  These are


  6   indicated for long-term use.  As I said before,


  7   their efficacy over the loan haul, over the one to


  8   two years of exposure in the clinical trials, is


  9   about along the lines of the earlier products


 10   approved for short-term use.


 11             [Slide]


 12             With regard to barriers, as I said, I will


 13   mention just one, and this relates to the safety


 14   exposures that have been required of sponsors


 15   working in this area.  The FDA has stated a minimum


 16   of 1,500 patients for one year should be exposed to


 17   these products prior to submission of an NDA, and


 18   that 200-500 patients complete a second year to get


 19   an understanding of durable efficacy and safety.


 20             Those who have held that this might be too


 21   rigorous have evoked the International Conference


 22   on Harmonization E1A document on the development of




  1   drugs for long-term treatment of


  2   non-life-threatening conditions which cite 300-600


  3   patients for 6 months and 100 for 1 year.  They


  4   cite also 1,500 patients total in all of the


  5   studies, including Phase I.


  6             [Slide]


  7             But that document also explains that


  8   longer and larger exposures are readily


  9   rationalized and perhaps necessary if the benefit


 10   of the drug is noted or expected to be small,


 11   experienced only by a fraction of treated patients


 12   and of uncertain magnitude as in reliance on a


 13   surrogate, such as weight loss.


 14             I think this characterizes the state of


 15   the evidence and the state of the efficacy with


 16   these products and it is really our rationale


 17   behind requiring larger exposures.  Also, I think


 18   we all understand, as has been said many times


 19   today, that the magnitude of this epidemic is such


 20   that the anticipated target populations in


 21   open-market use is absolutely astronomical and it


 22   is our responsibility to be as sure as we can be




  1   that drugs are going to be safe and effective when


  2   they go out into these millions and millions of


  3   patients.


  4             [Slide]


  5             With regard to therapeutic gaps and


  6   unanswered questions, one of the issues that really


  7   we believe bears further investigation is


  8   head-to-head comparisons of approved agents.  This


  9   is an issue that comes up in a lot of different


 10   fields of medical therapeutics and is certainly one


 11   in which I think patients and physicians are


 12   under-served by the pharmaceutical and clinical


 13   investigational communities as a means of providing


 14   evidence for individualized, rational choices in


 15   treatment.


 16             [Slide]


 17             Long-term safety and efficacy of older


 18   drugs also needs better understanding, particularly


 19   phentermine.


 20             [Slide]


 21             I show you this slide of drug use data


 22   from 1991-2002 to demonstrate that throughout these




  1   last 12-plus years phentermine leads the pack with


  2   regard to U.S. prescriptions.  These were projected


  3   prescriptions for 2002 but I think they were borne


  4   out, and also projected for 2003.  Phentermine


  5   prescriptions are double those for sibutramine and


  6   Orlistat, yet, this is a drug that is approved only


  7   for short-term use.  It is likely that in this


  8   context it is being used for long-term use and we


  9   really are poorly informed as to its long-term


 10   safety and efficacy.


 11             [Slide]


 12             Studies of combination therapy, in order


 13   that we can better label these drugs, are also


 14   necessary and, parenthetically, studies of drug


 15   cycling which I believe are commonplace in


 16   therapeutic interventions in obesity--more


 17   information is required for purposes of drug


 18   labeling.   Finally, the "Holy Grail" that is the


 19   question that we all yearn for an answer about, and


 20   that is, do the drugs that we are going to use in


 21   this area, both today's and tomorrow's, confer


 22   long-term individual and population reductions in




  1   morbid and mortal sequelae of obesity?


  2             [Slide]


  3             Finally, or actually next to finally, I


  4   want to read you another quote, and this is from J.


  5   Diamond, writing an interesting piece that he


  6   published in Nature last year.  The piece is really


  7   about the worldwide epidemic of type 2 diabetes,


  8   diabetes and obesity that humans generally,


  9   although some more than others, are programmed as a


 10   result of energy economy genes in the aggregate to


 11   develop when food is overly abundant.  That is


 12   obviously why we are here today.  In discussing


 13   this problem he states that an epidemic of a


 14   genetic disease waxes because of a rise in


 15   environmental risk factors, and then wanes when the


 16   number of susceptible potential victims falls, but


 17   only because of the preferential deaths of those


 18   who are genetically more susceptible.


 19             This is a sobering concept and that is why


 20   I wanted to bring it to our attention.  However


 21   long obesity has been a problem, it is clear that


 22   we are still on the waxing side of this story. 




  1   When the obesity and type 2 diabetes epidemics


  2   begin to wane we want it to be because of the


  3   success of our interventions and not because of a


  4   culling of the susceptibles.


  5             [Slide]


  6             In conclusion, from the standpoint of the


  7   therapeutic subgroup the magnitude of the obesity


  8   epidemic, its contribution to chronic disease, its


  9   costs to individuals and society, and the absence


 10   of broadly effective therapeutics constitute a call


 11   to action by the collective medical community,


 12   including FDA, and we are certainly committed in


 13   that regard.


 14             Resolution of issues around real or


 15   perceived barriers to development is paramount to


 16   advancing the field of obesity therapeutics, though


 17   we want to emphasize that this must be without


 18   sacrificing the overall quality of the obesity


 19   armamentarium.


 20             With that, diet and exercise remain the


 21   mainstays of prevention and treatment of obesity;


 22   drugs are adjunctive to hygienic measures.  They




  1   were yesterday, they are today and they will be


  2   tomorrow we believe.


  3             Precedent with older as well as newer


  4   drugs, reliance on weight loss alone as a measure


  5   of health effects of these products directs a


  6   cautious, measured approach in obesity


  7   therapeutics.  Questions, among others, of


  8   comparative efficacy and safety, long-term clinical


  9   outcomes of treatment and effects of combination


 10   therapy regimens must be addressed sooner rather


 11   than later.  Thank you very much.


 12             DR. SHINE:  Thank you very much.  I think


 13   we will go ahead and have Dr. Acheson make his


 14   presentation and then it looks like we may have a


 15   few minutes before the break to inquire about both


 16   of these presentations.


 17             David Acheson is Director of Food Safety


 18   and Security Staff in the Center for Food Safety


 19   and Applied Nutrition, and he is going to discuss


 20   issues related to obesity and research.


 21                        Obesity - Research


 22             DR. ACHESON:  Good morning and thank you,




  1   Dr. Shine, for that introduction.


  2             [Slide]


  3             What I am proposing to do over the next


  4   few minutes is really to describe the process that


  5   the obesity subgroup of the FDA obesity work group


  6   underwent to begin to address the issue of obesity


  7   research.  This clearly is an enormous area and so


  8   I want to begin with really just a focus on what


  9   the overall approach was for this.  One of the


 10   mandates for the obesity work group was to identify


 11   the applied basic research needs that include the


 12   development of healthier foods, as well as a better


 13   understanding of consumer behavior and motivation.


 14             [Slide]


 15             The overall approach that we took here was


 16   really to begin with focusing on research topics


 17   that were mission-relevant to FDA.  When we began


 18   to think about research in the context of obesity,


 19   clearly, there is an enormous amount of research


 20   going on and we needed to focus it down and target


 21   it towards FDA relevant issues.


 22             The approach that we took to try to do




  1   this was to think through and to document current


  2   and relevant research that was related to these


  3   mission-relevant topics, and I am going to go


  4   through some of those, and based on that, then to


  5   identify knowledge gaps.  Essentially, my


  6   presentation is set up to look at some of the


  7   research issues and subsequent knowledge gaps.


  8             [Slide]


  9             As we discussed this, we really tried to


 10   narrow this down and came up with three principal


 11   areas.  The first was in relation to labeling and I


 12   would say this is probably one of the largest areas


 13   that we discussed.  The labeling was broken down


 14   into labeling in relation to restaurants and


 15   labeling in relation to the Nutrition Facts Panel.


 16             We also considered translational research,


 17   and where I am going there is in relation to some


 18   of the translation between the basic science and


 19   the mission-relevant issues for FDA.  We identified


 20   three areas there that are of potential relevance:


 21   the first, neonatal imprinting; second, "omics",


 22   essentially genomics, proteomics and metabolomics;




  1   and, thirdly, the impact of caloric restriction and


  2   what research there was going on in FDA and other


  3   areas that was related to that.


  4             The third point was just to consider the


  5   other areas.  You just heard from Dr. Orloff


  6   extensive discussion about drugs in relation to


  7   obesity.  But we also wanted to consider drugs and


  8   devices, food additives and dietary supplements


  9   and, essentially, those areas were largely excluded


 10   from our consideration because they weren't mission


 11   relevant research for FDA.  I am not saying that


 12   they are not relevant to the quest of tackling the


 13   obesity problem but, as you will see, my


 14   presentation doesn't cover those in any great


 15   detail and the explanation is really that the


 16   research in those areas is not relevant to the


 17   mission of FDA.


 18             [Slide]


 19             So, to focus firstly on the labeling


 20   research, the current research and some research


 21   that was undertaken once the obesity work group was


 22   established worked through the root of focus




  1   groups.  One of the areas that was addressed was


  2   restaurant labeling and to determine consumer


  3   reactions to menus that include caloric information


  4   and, essentially, to ask the question whether, if


  5   you provide caloric information on a menu, it makes


  6   a difference to consumers' choice.


  7             The second area in relation to the food


  8   label was to consider consumer reactions to the


  9   nutrition facts panel.  Obviously, there is a


 10   limited amount of information you can get on a


 11   facts panel, but what are the critical elements


 12   that one needs to get on?  Some of the areas that


 13   were addressed there were the issue of calories of


 14   the daily value, what did the consumers understand


 15   by that; what the impact would be of eliminating


 16   the calories from the fat section of the nutrition


 17   facts panel; and then to consider what the impact


 18   would be on adding more information on


 19   multi-serving packages to show the actual calories


 20   and the percent daily value in the package.


 21             Where we were going there was essentially


 22   that if you look at items that are typically




  1   consumed in a single serving, such as a muffin, it


  2   may be labeled in such a way that it is considered


  3   that a muffin is two servings and not many of us


  4   going to consume just half a muffin and put it on


  5   the side for consuming later.  So, it was more


  6   logical to think through the total amount of


  7   calories of the serving.


  8             Obviously, the third point was to consider


  9   messages and to determine what is the most


 10   effective message for conveying these nutritional


 11   issues.


 12             [Slide]


 13             As part of this, FDA has been involved in


 14   the development of a social sciences model to help


 15   determine the factors that influence dietary and


 16   weight management.  That has really involved three


 17   areas  The first is the review of literature to try


 18   to identify factors that affect food behavior and


 19   to catalog existing data; the second, to develop a


 20   quantitative model really to get at what an


 21   individual's decisions are affecting weight.  This


 22   works into physical activity and choice of food and




  1   that, obviously, involves attitudes, behaviors and


  2   environmental factors.  Then, to get into the issue


  3   of cost benefit analysis and the role of food


  4   labeling regulation and the development of policy.


  5             [Slide]


  6             Some of the consumer perceptions and


  7   attitudes--and this is just a brief summary--are


  8   listed on this slide.  Some of the things that we


  9   learned from this brief study of the research


 10   environment was the perception of overweight versus


 11   obesity and the fact that, in fact, most or many


 12   consumers don't consider overweight as a "problem"


 13   and indicate that it is of little consequence to


 14   consumers.  It is different with obesity, but just


 15   simply being overweight is not a significant


 16   consequence.


 17             Secondly, the perception of a person's


 18   weight and typically adults and teenagers


 19   mis-perceive their weight.  Men tend to


 20   underestimate their weight and healthy, underweight


 21   women tend to overestimate their weight.  Also,


 22   parents misjudge the weight of their children and




  1   will often determine that their children are at


  2   healthy weight where, in fact, they may be a little


  3   overweight.


  4             The third point is what consumers'


  5   perception is of their diet, and there is a


  6   tendency to think that generally you are eating a


  7   more healthy diet than you actually are.  If you


  8   analyze the content of the diet, the perception


  9   certainly is that you are eating better than, in


 10   fact, you are eating.


 11             Some of the recent focus groups have


 12   really tried to target parents and children.


 13   Obviously, part of our thinking here was the


 14   research in relation to product obesity and trying


 15   to work on that angle of it.


 16             The second point there is the perception


 17   of obesity, which I have alluded to, in terms of


 18   access for information and the perceived barriers


 19   and the motivating factors that will allow people


 20   to alter these perceptions.


 21             The conclusion of all of this was that


 22   there is emphasis on incremental change.  I think




  1   as you have already heard, nothing is going to


  2   happen here quickly.  Also, we have to be cautious


  3   of over-saturation of consumers.  They obviously


  4   want to receive health information but we have to


  5   do this in a targeted, judged and careful way.


  6   Finally, the focus on child education, I think, was


  7   a very clear message as an area of research in


  8   relation to this whole consumer aspect that has to


  9   be considered as an important focus.


 10             [Slide]


 11             The knowledge gaps: the first knowledge


 12   gap that comes out of this is information used to


 13   facilitate consumers' weight management decisions.


 14   There is a very clear need for research in this in


 15   both a qualitative and quantitative fashion.  I


 16   have just summarized three points there.  Firstly,


 17   the consumer reaction to the food label.  I have


 18   gone over some of the issues there, but what are


 19   the advantages of highlighting the calories, or


 20   listing the quantitative amounts of nutrients in


 21   multi-size packages?  Our initial focus groups


 22   indicated that these are important areas.  What we




  1   need now is to take this into quantitative research


  2   to really document the impact that we might get


  3   from some of these changes.


  4             The second point, the consumer reaction to


  5   and the effectiveness of restaurant nutrition


  6   information.  Does it make a difference if we list


  7   the information about the calories, the fat, the


  8   sodium next to the items on the menu list when you


  9   go to a fast-food environment?


 10             Finally, the consumer's dietary behavior


 11   and attitudes toward weight management, which


 12   obviously encompasses what I have already talked


 13   about but gets into the area of physical activity


 14   as well.


 15             [Slide]


 16             The second knowledge gap is the


 17   relationship between obesity and food consumption


 18   patterns.  Where we are going there is essentially


 19   the relationship between obesity and the frequency


 20   of foods consumed in different locations.  The


 21   target there is to examine the impact of consuming


 22   food in the home environment versus the fast-food




  1   environment versus a restaurant environment, and


  2   does it make a difference in terms of the frequency


  3   and the types of foods that are consumed in those


  4   environments?


  5             Also, we recognize that there is an


  6   important impact of both socioeconomic status in


  7   this as well as ethnic background, and there is a


  8   very clear need to generate data in relation to


  9   both of those issues.


 10             Finally in this second knowledge gap are


 11   the factors that actually contribute to overeating.


 12   Obviously, those are encompassed with many of the


 13   things I have already discussed, but what is the


 14   role of the super-size portion in all of this, and


 15   that really needs to be investigated.  I am just


 16   using that as an example of factors that would


 17   contribute to overeating.


 18             [Slide]


 19             The second area is in relation to


 20   formulation research, and really what this was


 21   addressing was what do we know about the factors


 22   that will drive reformulation to develop healthier




  1   foods?  The questions that were posed there were


  2   whether current regulations offer a barrier or an


  3   incentive to the production of healthier foods.


  4   The research that is currently ongoing there is


  5   that there are currently discussions with key


  6   industry personnel, and this is being done through


  7   a third-party contractor, so that we can get some


  8   insight into the barrier and regulatory hurdles


  9   that may be present that could impact product


 10   reformulation to develop healthier food.


 11             The third bullet there gets into the


 12   issues focused on manufacturers--what they can put


 13   on the label; what claims they can make; possible


 14   changes in regulations that would facilitate


 15   healthier foods; and what incentives we may be able


 16   to put in place, as a regulatory agency, that would


 17   encourage the development of healthier foods.


 18             [Slide]


 19             So, the third knowledge gap in relation to


 20   this product reformulation is where do we need to


 21   go?  What do we need to do?  We really need to


 22   further explore these barriers.  As I said, there




  1   is research that is going to give some pointers but


  2   the three key areas there are, firstly, do


  3   incentives, e.g., label prominence, impact industry


  4   on the development of healthier foods.  What is


  5   going to drive them to do that?  Do the barriers,


  6   e.g., regulatory hurdles, have an impact on the


  7   development of healthier foods?  We really need to


  8   understand that, understand what those hurdles are


  9   and, if possible, see what we can do to get around


 10   them.  Obviously, the third point there, once we


 11   have tried to balance the incentives and the


 12   hurdles, is how can these be addressed.


 13             [Slide]


 14             The next area in relation to drugs,


 15   devices, food additives and dietary supplements--as


 16   I mentioned, this was not a primary focus for the


 17   reasons that I have already given.


 18             [Slide]


 19             However, we did identify one knowledge gap


 20   here that we thought was important.  That was the


 21   potential for FDA-regulated products to be


 22   unintentionally contributing to the obesity




  1   problem.  The two points there were to consider


  2   whether weight gain may be an unintended and


  3   unrecognized complication of certain medications.


  4   Obviously, there are examples of that.  A research


  5   gap here or a research need is that this has not


  6   been consistently measured.  It has not been


  7   consistently evaluated, and we need to consider


  8   whether this should be an adverse effect that has


  9   to be taken into account in the approval of a drug.


 10             So the sub-bullets there are that, first


 11   of all, we have to determine if this is a problem.


 12   We identified it as a knowledge gap, and I


 13   emphasize knowledge gap.  We have to figure out


 14   whether it is a problem that needs to be addressed.


 15             Then, obviously, the corollary of that is


 16   to develop animal models to study the long-term


 17   effects on weight management and medications.


 18   Obviously, animal models can go in many other


 19   directions too but the issue of unintended


 20   consequences of a drug that is taken for a


 21   completely unrelated reason could be tested through


 22   appropriate animal models.




  1             [Slide]


  2             Finally, there is the basic science


  3   component of this.  I mentioned the three areas:


  4   Neonatal imprinting, and where we were going there


  5   was to try to get a better understanding of the


  6   impact of developmental programming, particularly


  7   during early development so, obviously, fetal


  8   exposure, neonatal exposure, infant exposure when


  9   these metabolic pathways are being


 10   established--does what mommy eats when she is


 11   pregnant, does what the neonate is fed or the young


 12   infant fed, what is the impact of that on


 13   subsequent development of obesity?  Part of our


 14   thinking on neonatal imprinting was the impact of


 15   infant formula often on childhood obesity and


 16   subsequent adult obesity.  Certainly, an area there


 17   that is of interest is the push towards different


 18   types of formula, without really I think major


 19   consideration on the impact of the obesity issue in


 20   relation to new formulas.


 21             The second area is obviously the "omics"


 22   issue to identify susceptibilities.  This is really




  1   getting at linking genetic susceptibilities.


  2   Obviously, this goes beyond just the susceptibility


  3   to obesity but the susceptibility of obese people


  4   to develop other problems such as type 2 diabetes.


  5   A clear area there is through genomics and


  6   subsequently proteomics and then metabolomics to


  7   really get a better handle on how that all fits


  8   together.


  9             Finally, the effects of caloric


 10   restriction, and over the last ten years NCTR has


 11   placed some emphasis on this.  They have been


 12   working on that and have been looking at the effect


 13   of caloric restriction, and this is in relation to


 14   free radical formation, malignant tumor rates and


 15   "less than ad lib" feeding on rapid weight


 16   reduction.  so, there is also a need there in terms


 17   of further research.


 18             [Slide]


 19             The fifth knowledge gap relates to this


 20   area of translational research, and we felt that it


 21   was essential that FDA use basic research to drive


 22   and develop regulatory policies.  This is obviously




  1   going to be especially with NIH but also many or


  2   the other stakeholders.


  3             Just as a small aside there, I was


  4   recently at a meeting at NIH where I presented some


  5   of what we have been doing and, interestingly,


  6   while there was a lot of discussion about the basic


  7   metabolic pathways and many of the potential drug


  8   therapies that Dr. Orloff discussed were raised,


  9   the group really was beginning to focus on that


 10   obviously a lot of this is about calories, and to


 11   get a better understanding of caloric management


 12   and some of the "social" sciences around food


 13   intake.


 14             But the knowledge gaps here include


 15   obviously the area of getting a better


 16   understanding of developmental imprinting, the use


 17   of "omics" and the development of animal models for


 18   the effects of diet, drug therapy and long-term


 19   weight maintenance.  So, there are some common


 20   themes there.


 21             [Slide]


 22             To conclude, obviously, calories are a




  1   critical element and the research that we were


  2   focused on was really how can we, having taken that


  3   basic premise that calories are what this is all


  4   about--how can we focus our research to get at


  5   that.  Probably the most critical element of all of


  6   this is understanding consumers.  We need to


  7   understand food labeling and how the consumers


  8   react to it; their eating habits and their weight


  9   management.  When we have a better understanding of


 10   that, we can then use food labels, education


 11   programs or whatever to try to move in the right


 12   direction.


 13             The third point there is the development


 14   of healthier foods.  I have already discussed that


 15   obviously in the context of what can we do as a


 16   regulatory agency to encourage healthier food


 17   development, and then, finally, the input from


 18   basic research in the development of regulatory


 19   policy which is always an underpinning, the good


 20   science has to be there first to move forward.


 21   Thank you very much.


 22             DR. SHINE:  Thank you very much.  We have




  1   an opportunity now, before our break, to engage our


  2   three speakers on any issues that the committee


  3   would like to raise.  What kinds of questions or


  4   issues would you like to inquire about?  Xavier?


  5             DR. PI-SUNYER:  I would just like to ask


  6   Dr. Orloff--I agree with him completely about the


  7   need to do studies of combination therapy to look


  8   at either the safety or the efficacy of combination


  9   drugs, but as he knows and I know, the drug


 10   companies only want to test their own drug and not


 11   a combination because of the expense of doing that.


 12   So, how would he propose that this get done?


 13             DR. ORLOFF:  Well, the first thing is that


 14   this is a problem obviously, as you point out,


 15   during the patent life of drugs.  I suppose, to


 16   some extent, the community would have to give


 17   thought to really how large and long the


 18   combination therapy trials might actually have to


 19   be.  Again, I am just thinking off the top of my


 20   head here but it occurs to me that if the long-term


 21   safety and efficacy of the individual products has


 22   been established as a basis on which they have been




  1   approved by the FDA, then that principle stands


  2   and, obviously, on a case-by-case basis this would


  3   have to be considered but it seems reasonable to


  4   think that we might be able to prove principle of


  5   efficacy and acceptable safety of combinations,


  6   perhaps not to the standards of directing labeling


  7   but certainly to a standards that would provide


  8   some guidance to physicians in this field, thus,


  9   standards for publication in peer-reviewed journals


 10   which, for better or for worse, is not always the


 11   same as standards for labeling.  So, that is one


 12   possibility.


 13             FDA cannot force drug companies to do


 14   trials with drugs other than their own unless, I


 15   suppose, there was some clear-cut rationale, for


 16   example, that the combination of drug with another


 17   was such that it spared toxicity of the proprietary


 18   drug and FDA stated that they would be really


 19   unwilling to approve--and this would be precedent


 20   setting--the proprietary drug at its optimal


 21   effective dose but would consider approving it in


 22   combination with another product which was still




  1   effective, the two together, but where the toxicity


  2   was spared.  Those are just a few thoughts.


  3             DR. SHINE:  Dr. Orloff, just to follow-up


  4   on another element here, you quite appropriately


  5   showed that obesity is a chronic illness and that


  6   it is likely that one might have to think about it


  7   much like hypertension in that it may require


  8   lifetime treatment.  What do we know about the


  9   capacity to select individuals who, in fact, might


 10   be most effectively treated with drugs long term in


 11   terms of either their behavioral characteristics or


 12   their genetic characteristics?  That is, could one


 13   stratify the obese population into categories where


 14   it would make more sense to make major efforts with


 15   drug therapy as opposed to other kinds of


 16   approaches?


 17             DR. ORLOFF:  I don't think we have that


 18   information available to us.  I am certainly not


 19   the expert to give the definitive answer but what


 20   you have touched on is clearly a problem that is


 21   active in all areas of medical therapeutics, and it


 22   is the great hope for obesity, as well as you




  1   suggested for hypertension and other sort of risk


  2   factor modification approaches to disease


  3   prevention, that we would be better up-front at


  4   identifying patients, on the one hand, who are at


  5   greatest risk for the sequelae--and we are better


  6   and better at doing that for cardiovascular disease


  7   risk based on biomarkers and such--but, on the


  8   other hand, are likely to benefit most from the


  9   drug from the standpoint of, for example,


 10   pharmacogenomic directed responsiveness.  I don't


 11   know if anybody else around the table--Dr.


 12   Pi-Sunyer, if you have any thoughts on where the


 13   state of the science is there.


 14             DR. PI-SUNYER:  No, I think that is a very


 15   good point but I think we are not there in terms of


 16   knowledge that we can select people who we know


 17   will get a better effect or are less likely to have


 18   safety problems with a drug than others.


 19             DR. SHINE:  I am fascinated by the


 20   implications of the fat gene argument made by Jerry


 21   Diamond and a number of other people, including the


 22   Rockefeller people, and the question again of




  1   whether over some period of time we could identify


  2   targets that are more likely to be responsive than


  3   others.


  4             Both of you touched on this, but in terms


  5   of the science one of the biggest gaps we have is


  6   the research on behavior and how and in what way we


  7   can influence behavior.  We know that for a whole


  8   variety of other addictions the only way that one


  9   is usually successful in dealing with tobacco or


 10   alcohol, or whatever, is total cessation.


 11   Unfortunately, that doesn't work for obesity.


 12             DR. ORLOFF:  Yes, I think it is an


 13   interesting point that overall poor or less than


 14   satisfactory outcomes in obesity treatment, even in


 15   patients who remain on drugs, is a combination


 16   likely of at least two factors.  One is perhaps


 17   that in truth the efficacy of the drug wanes but


 18   probably more than likely because the behavioral


 19   components that determine the ultimate success of


 20   the intervention are, you know, that the patient


 21   falls off the wagon, if you will.  I talked about


 22   the concept of drug cycling, which I gather is




  1   utilized by a number of obesity docs.  The degree


  2   to which it is successful after the first couple of


  3   cycles I think is in question.


  4             DR. SHINE:  Dr. Swanson?


  5             DR. SWANSON:  This is a question for Dr.


  6   Acheson.  Building on the behavioral issue, we all


  7   know that part of the issue is that calories count


  8   but it is an intake-output balance that is


  9   necessary.  Was the consideration of how to


 10   motivate people to expend more energy or some kind


 11   of a link between X number of calories--to eat this


 12   thing that contains X number of calories you would


 13   need to expend so many steps?  Or, was that out of


 14   scope because it is kind of out of FDA's purview?


 15             DR. ACHESON:  Well, it certainly was


 16   discussed, Dr. Swanson.  The issue of caloric


 17   balance is obviously input-output.  Unfortunately


 18   FDA can't regulate exercise.  If we could, maybe we


 19   would solve the problem.  But what we did there, we


 20   had a number of presentations from people who are


 21   involved in that.


 22             For example, the VA has a program that




  1   they are just initiating called "Move" in which


  2   they are essentially identifying their obese at


  3   various points through their healthcare system and


  4   enrolling them, as much as possible, in some kind


  5   of exercise and weight management program.  So,


  6   they are trying to tackle it from both sides.  Our


  7   approach was, well, what can we do on a label, etc.


  8   that is going to have an impact, and that is half


  9   the story.  You are right, it is not just


 10   understanding caloric intake; it is also output.


 11   So, we didn't ignore it.  We need to partner with


 12   people to try to get that piece across.


 13             DR. SWANSON:  I just think that,


 14   considered from a prevention aspect, rather than


 15   targeting obese or overweight people and this is


 16   what you need to get the pounds off, another


 17   approach that I really haven't seen is how do you


 18   prevent the pounds from going on, and you can have


 19   the super-size meal if you walk to a certain


 20   restaurant versus driving.


 21             DR. ACHESON:  I totally agree and that is


 22   part of understanding consumer behavior.  There is




  1   no question that that is important.  Also, I think


  2   let's try and get in there and prevent the problem


  3   before it ever starts.


  4             DR. SHINE:  Let me follow-up on that.  The


  5   experience with tobacco is that you can do


  6   substantial amounts of public education.  You can


  7   probably change the overall attitudes of a subject


  8   but, in fact, much of the progress made in tobacco


  9   was related to taxing tobacco; to changing the


 10   environment in which people could smoke, and so


 11   forth.  In the case of obesity, clearly there is no


 12   population that is at greater risk than children


 13   where, on the one hand as Dr. Swanson points out,


 14   physical exercise--gym is often gone from the


 15   curriculum but, on the other hand, they are being


 16   exposed to a substantial amount of fast foods.


 17             I was impressed by the way in which in


 18   your focus groups you identified that consumers


 19   like to get the information about a group of foods


 20   that they would likely eat together, the burger


 21   example of the combination of fries, Cokes, and so


 22   on and so forth.  My question is whether an




  1   appropriate target would be schools and school


  2   administrators around the combination of what kids


  3   are eating in school to try to educate them and


  4   their parents as to what the risks are in having


  5   access to what in many institutions is just awful.


  6   Now, some school districts are clearly making an


  7   attempt to modify that but changing the environment


  8   by virtue of changing what is available to kids


  9   might be a very important strategy here, and there


 10   the FDA might be able to come up with some labeling


 11   activities, similar to the way in which you have


 12   grouped the information about burgers, in a way


 13   that would be useful to administrators and PTAs.


 14             DR. ACHESON:  I agree with you.  It does


 15   focus on the product population which is possibly


 16   the primary target here.  I think that is one


 17   avenue to pursue.  Obviously, schools have many


 18   things that they have to deal with and think about,


 19   and this would just be one component of managing a


 20   child's life, so to speak, to try to control their


 21   diet.


 22             That speaks also to developing educational




  1   programs to help parents understand the importance


  2   of caloric balance for their children.  Maybe that


  3   could be done through the schools as well,


  4   potentially working with the school lunch program,


  5   for example, to try to think about healthier foods


  6   in that context.  So, I agree with you.  It is


  7   certainly an avenue that one should consider.


  8             DR. SHINE:  What I am arguing about is not


  9   just about the education; it is actually changing


 10   the environment in a substantial way.  Dr. Roses?


 11             DR. ROSES:  I was also going to make the


 12   point about the only reason that we eat is so we


 13   can burn the calories, and if you are only


 14   measuring one side of the equation as part of the


 15   studies that are done and as part of the advice we


 16   give we may be just dealing with, one might say, a


 17   minor part of the problem.


 18             I was pleased to hear that there is now an


 19   acceptability that we are genetically different and


 20   we have different susceptibilities, and some of us


 21   will gain weight on different calories and others


 22   won't.  But I think, rather than be in the second




  1   point about "omics" as if there were some magic in


  2   applying techniques to biological problems, there


  3   is some evidence already that we can stratify


  4   populations by their genetic polymorphisms.  For


  5   instance, this room could be stratified by your


  6   blood types.  However, just in the beginning state,


  7   the science called pharmacogenetics is applying


  8   that to responders versus non-responders the


  9   extremes of a drug trial.


 10             With our experience with a recent


 11   candidate, in a very small study which is in the


 12   public domain and I can show it if you like in a


 13   single slide, we were able to put stratifying


 14   markers in a very simple way on people who were the


 15   big responders and people who could not respond and


 16   people who, by the way, had a difference in weight


 17   gain if they gained weight on the drug.


 18             The third part has to do with head-to-head


 19   trials.  Head-to-head trials take the average group


 20   of patients and they test them against a drug.  But


 21   in the world of stratification comparing one third


 22   that might respond that might respond in this group




  1   with the one third that might respond in this group


  2   is not really head-to-head, and it is now possible


  3   to stratify people by their metabolic enzymes, by


  4   their markers, by a variety of other things so that


  5   we can truly do, if you are interested in making


  6   that a gold standard, head-to-head trials that at


  7   least have some common denominators.


  8             DR. SHINE:  Any comments?  If not, I am


  9   going to take the chair's prerogative and go to a


 10   break.  We are going to have an opportunity after


 11   the next speaker to have a continued discussion,


 12   and I presume you will be available for further


 13   conversation.  Let's go ahead and take a break.  We


 14   will reconvene at 9:45.  Thank you.


 15             [Brief recess]


 16             DR. SHINE:  We will come back to our


 17   discussion after the next presentation.  We are


 18   pleased that Alan Rulis, Senior Advisor for Special


 19   Projects in the Center for Food Safety and Applied


 20   Nutrition, will tell us about the highlights of the


 21   obesity working group report.  Alan?


 22          Highlights of the Obesity Working Group Report




  1             DR. RULIS:  Thank you, Chairman.


  2             [Slide]


  3             I am Alan Rulis.  I am currently Senior


  4   Advisor for Special Projects in the Center for Food


  5   Safety and Applied Nutrition.  I have been involved


  6   with the obesity working group writing team and


  7   throughout the process of putting that report


  8   together.


  9             To summarize very briefly, the report


 10   recommends a number of thrusts in several different


 11   areas that you are all aware of now, in particular


 12   the food label and in particular there calories,


 13   serving size, claims and so forth, even the issue


 14   of carbohydrates.  We have recommendations in the


 15   report about enforcement against products with


 16   misleading weight loss claims and, as you have


 17   heard this morning, there are sections that deal


 18   with therapeutics and research.


 19             [Slide]


 20             What I would like to focus on in my


 21   presentation is a couple of other areas that are


 22   extremely important to the success of FDA's efforts




  1   to stem the tide of obesity.  They relate to


  2   education and restaurants, under the rubric of


  3   trying to find means by which we can get around the


  4   table the people involved in these issues, not just


  5   the agency but stakeholders, educators, industry,


  6   consumer groups, and so forth, to discuss next


  7   steps and to move forward, to make some sort of


  8   forward progress.


  9             In that regard, the report does recommend


 10   in fact that the FDA use a third-party facilitator


 11   as a convener to essentially create a national


 12   dialogue on obesity.  So, what I would like to


 13   cover in my remarks this morning are some slides


 14   that relate to development of that national


 15   dialogue by means of a facilitator to get the


 16   discussion going.


 17             I looked over my slides and realized that


 18   25 of my 30 slides are really questions.  Of the


 19   last 12, 9 of them are questions to the Board.  So,


 20   my slides will be primarily in that vein, looking


 21   forward to your insights, comments, recommendations


 22   and feedback to us.




  1             As I said, the report does in fact


  2   recommend that FDA work through a facilitator to


  3   provide a forum for stakeholders to seek a


  4   consensus-based approach that addresses two


  5   specific aspects of obesity in the United States,


  6   in particular, developing options for providing


  7   voluntary nutrition information for foods consumed


  8   away from home, for example in the restaurant


  9   setting and, secondly, education to combat product


 10   obesity.


 11             The reasons are quite obvious.  We know


 12   that Americans now spend about 46 percent of their


 13   food budget on food eaten outside the home, as our


 14   report states.  We also know that body weight and


 15   trends towards obesity that begin at puberty or in


 16   adolescence are often propagated through adulthood


 17   and are very difficult to reverse.  So, we think


 18   that those are two prime areas for establishing a


 19   dialogue.


 20             [Slide]


 21             With respect to foods eaten away from


 22   home, we imagined putting together a contract for a




  1   facilitator to start the dialogue and we imagined


  2   having the facilitator address the following


  3   questions:  What nutrition information would be the


  4   most helpful for consumers to have before ordering


  5   food in a restaurant?


  6             [Slide]


  7             What are the best options for providing


  8   nutrition information in a restaurant setting?  We


  9   have had many discussions with the restaurant


 10   industry throughout the course of the obesity


 11   working group's efforts focused on this question.


 12   It is a complicated question because the restaurant


 13   industry is very diverse.  There are quick service


 14   restaurants where people walk in and get their meal


 15   right away and there are others where there are


 16   white tablecloths and meals are prepared to order,


 17   and there are a lot of specific changes that are


 18   made to menu items by the cook.  It is very


 19   difficult to say that there is one set of best


 20   options, of course.


 21             [Slide]


 22             Should nutrition information be listed for




  1   all menu items or just some items?  What are the


  2   practical considerations there?  If we do have


  3   restaurants put information on some menu items,


  4   then what criteria should determine which items


  5   should have nutrition information listed?  We have,


  6   as a matter of fact, a very interesting menu right


  7   now in the agency from a major chain restaurant


  8   that has caloric information next to all of the


  9   menu items and it is very interesting, very


 10   remarkable to look at because you are not used to


 11   seeing it but it can be done and it is there.


 12             [Slide]


 13             When providing nutrition information in


 14   the restaurant setting, what consideration should


 15   be given to the differences between chain and


 16   non-chain restaurants?  Of course, that relates to


 17   the whole question of the diversity of that segment


 18   of the industry.


 19             [Slide]


 20             How should restaurants tailor the kinds of


 21   nutrition information presented based on expected


 22   clientele?  You can imagine the need there to focus




  1   the kinds of information that is presented to the


  2   type of restaurant and the clientele that frequent


  3   that restaurant.


  4             [Slide]


  5             Number six, should nutrition information


  6   be presented in context, for example, as a percent


  7   of daily value, comparing for example to a 2,000


  8   calorie per day diet or, for example, comparing to


  9   other menu items?  This is something that I think


 10   many consumers would find very helpful, the notion


 11   that when you walk into a restaurant and order an


 12   item off the menu, you have some sense of whether


 13   consuming that item is going to comprise 20 percent


 14   or 80 percent or 150 percent of your normal daily


 15   caloric intake.  That sort of feel for what that


 16   meal represents would be extremely helpful we think


 17   to restaurant patrons.


 18             [Slide]


 19             Number seven, how should FDA proceed to


 20   encourage restaurants to participate in a voluntary


 21   pilot program to test various options?  In the


 22   obesity working group report we say as part of the




  1   recommendations that we would like to see a pilot


  2   study conducted that would get into the question,


  3   in specific terms, about how such nutrition


  4   information, caloric information for example, could


  5   be placed at the point of sale for consumers to


  6   use, and we envision the restaurant industry coming


  7   with ideas about this.  We don't envision the FDA


  8   funding and creating such a pilot study out of thin


  9   air.  This is the kind of thing that would need to


 10   be done around the table, in communication with the


 11   industry and, thus, again the idea of a third-party


 12   facilitator.


 13             [Slide]


 14             Number eight, how can industry and Food


 15   and Drug Administration measure the effectiveness


 16   of providing nutrition information to consumers in


 17   restaurants?  One of the things we learned in our


 18   deliberations in the obesity working group is that


 19   information itself doesn't really necessarily


 20   answer the concern; that imparting information to


 21   people can be done but it is not necessarily


 22   absorbed and, once absorbed, it does not




  1   necessarily change behavior.  So, I think a


  2   pertinent question that we would pose to our


  3   third-party facilitator would be to get at the


  4   answer to this question.


  5             [Slide]


  6             On the subject of pediatric


  7   nutrition/obesity education, we have similar


  8   questions that we would like a facilitator to help


  9   us address.  On what age groups is it most


 10   appropriate for Food and Drug Administration to


 11   focus education efforts?  This is a sociological


 12   question as much as a pharmacodynamic one.


 13             [Slide]


 14             What are the most appropriate settings,


 15   for example school or home, health settings, social


 16   organizations or clubs, for such educational


 17   efforts?  Again, those of us who were on the


 18   obesity working group are well aware that there are


 19   many groups which have spent years working on these


 20   kinds of issues and know a lot about imparting


 21   information to children, to families and the


 22   pitfalls of trying to create an awareness about




  1   such subjects as obesity and then to change


  2   behavior.  It is very complicated.  It is almost an


  3   art form.  It is something that I think many of us


  4   at the agency are feeling like we really do need to


  5   have a participatory discussion about and, again,


  6   is another reason for having a third-party


  7   facilitator bring in people with different areas of


  8   expertise to get around this question.


  9             [Slide]


 10             Another question on the pediatric


 11   nutrition/obesity education issue is how important


 12   is it for education efforts to be conducted using


 13   mass media, for example television, radio and


 14   print?  When I think of adolescents today, they are


 15   wired, they are electronic, they are not reading


 16   newspapers; they are plugged in and they can be


 17   reached very effectively in many ways through the


 18   Internet, through the media, through the various


 19   things that they are tuned into constantly.  So, we


 20   need to be contemporaneous here.  We can't be


 21   thinking in terms of 20th century communication


 22   tools.




  1             [Slide]


  2             Over what time period should an education


  3   effort be extended to achieve optimal impact and


  4   lasting effects?  Another thing we learned in our


  5   deliberations in the group was that education is


  6   really not a short-term phenomenon.  It is possible


  7   to generate messages, to send them out and, you


  8   know, clean the dust off your hands and walk away


  9   and affect absolutely nothing.  What has to happen


 10   is that there needs to be a long-term effort that


 11   is continuous, that is reinforced and that has


 12   mid-course corrections to make it more effective.


 13             [Slide]


 14             What types of messages are the most


 15   effective, and in which age groups, for educating


 16   children about nutrition and health?  Again, this


 17   ties back into the question of prevention, the


 18   notion that if we can prevent adolescents or young


 19   people from starting on a path of being overweight


 20   we have done a whale of a lot more than we can do


 21   by worrying about how to get people who are


 22   currently overweight as adults to lose some weight.




  1   That is also important but it is extremely


  2   important to realize that once that pattern is set


  3   it is very hard to reverse.


  4             [Slide]


  5             To what extent should education and/or


  6   other types of messages be tailored to different


  7   ethnic and/or socioeconomic groups?  This is


  8   another issue we heard strong signals on in our


  9   facilitated discussions during the course of our


 10   obesity working group.  We are a heterogeneous


 11   nation, extremely so and becoming more so.  We have


 12   large numbers of immigrants coming to our country


 13   from different cultures where eating patterns and


 14   signals about what is right to eat and what is


 15   appropriate to eat, what is appropriate to feed


 16   your family are very, very different.  Even those


 17   of us who have been here a number of generations


 18   across our country have very different views about


 19   how we eat and what is appropriate.  So, we need to


 20   be able to tailor our efforts and I think our


 21   facilitator needs to be able to help us to do that.


 22             [Slide]




  1             Then, what are the effective means that we


  2   might be able to find for partnering in the public


  3   and private sectors to develop and deliver obesity


  4   education?  The Department of Health and Human


  5   Services has published a proposal in the Federal


  6   Register, last summer, that invited comments and


  7   suggestions on how to create public/private


  8   partnerships on a number of health issues that face


  9   the country, and this is one of them.  We are I


 10   think open to the question.  We would put the


 11   question to our third-party facilitator.  Let's get


 12   to the essential factors that help us partner with


 13   those stakeholder segments out there, the industry


 14   segment and the consumer segment and the citizen


 15   segment of our country, to get everybody around the


 16   table to chew on this issue.


 17             It is not simple because the FDA, as a


 18   regulatory agency, needs to be careful about how it


 19   does those things so it does not present either the


 20   appearance or the actuality of favoritism to any


 21   one company over other companies, and so forth.


 22   But we also do see the value of partnering.  A lot




  1   can be done that isn't regulatory in the


  2   traditional sense.  Talking to and working with


  3   effective partners on the outside can be extremely


  4   effective, and we would like our facilitator to


  5   help us uncover effective examples that are


  6   currently operating, and there are some.  We, at


  7   the FDA, are very familiar with the "Fight Back"


  8   campaign that was addressing the issue of microbial


  9   contamination of food and that is a very effective


 10   program that has educated a lot of people and


 11   prevented a lot of illness in this country.  It is


 12   a nice example of how that can work.  There are


 13   undoubtedly many others and we want to find out


 14   what they are, learn about what makes them


 15   successful and then adopt the aspects of them that


 16   make them successful to the programs that we would


 17   generate.


 18             [Slide]


 19             That brings me then to my last dozen


 20   slides or so on which there are still nine more


 21   questions, and these are really questions that go


 22   to the Board, and you have all seen them in your




  1   materials and I hope you have given them some


  2   thought.  They are focused on the two prongs of the


  3   issue as I have presented them here, namely, the


  4   scope of work that we would present to our


  5   contractor or third-party facilitator relating to


  6   food eaten away from home, and work on pediatric


  7   obesity education.


  8             Chairman, I would I guess defer to you in


  9   terms of how you want to proceed.  I can go through


 10   these questions quickly if you would like me to


 11   just to remind folks of what they are, and then we


 12   can kind of revisit them.


 13             DR. SHINE:  Why don't you go through them?


 14             DR. RULIS:  Okay.


 15             [Slide]


 16             Number one, are FDA's proposed questions


 17   and issues likely to provide appropriate


 18   information to proceed with a pilot program with


 19   restaurants?  In other words, are we asking the


 20   right questions here?  Are we missing something


 21   obvious?  We really need your thoughtful input and


 22   your recommendations about that.  If we haven't hit




  1   the target right on the head, then can you think of


  2   some other questions or issues that should be


  3   addressed and that we should have our facilitator


  4   focus on?


  5             [Slide]


  6             Secondly, what kind of evaluation is


  7   appropriate to assess the effectiveness of a pilot


  8   program?  As I mentioned, we wanted to get together


  9   and have the restaurant industry create some sort


 10   of program by which this can occur.  I should say


 11   very quickly that these programs are already going


 12   on out there.  You know, McDonalds and other


 13   companies have been in the news recently about


 14   programs that they are putting together to move the


 15   country in the right direction in terms of


 16   increased physical activity and wise food choices.


 17   So, we are well aware of that.  We want to engage


 18   with them on something specific in this context and


 19   so how do you evaluate the effectiveness of such a


 20   program?  I think we need your help on that.


 21             [Slide]


 22             What advice would you have for a




  1   facilitator?  If we were to go forward and contract


  2   out this work, what advice would you have for a


  3   facilitator concerning the basis for evaluating


  4   recommendations on providing nutrition information


  5   in a restaurant setting?  Again, are we targeting


  6   this right?  Have we asked the right questions or


  7   are we missing something obvious?


  8             [Slide]


  9             Fourth, what research would be helpful for


 10   a facilitator to know about to help them provide


 11   the best guidance to the agency on this subject?


 12   Again, you all, on the Board, have many different


 13   areas of research that you are familiar with.


 14   Perhaps you are aware of some that could be of


 15   value for us to hear about on the record today that


 16   could help us focus this in the right direction.


 17             [Slide]


 18             Fifth, in view of the materials that you


 19   have been provided, is there any other advice or


 20   information you believe is important to give the


 21   FDA on this issue?


 22             [Slide]




  1             That also goes for the pediatric obesity


  2   issues as well, and I will go through those


  3   questions briefly.  Are FDA's proposed questions


  4   and issues likely to provide appropriate


  5   information to guide the development of useful and


  6   understandable nutrition/obesity education efforts?


  7             I will tell you why I put


  8   nutrition/obesity on this slide.  In our


  9   discussions with people who have been doing this


 10   for years, they say one of the things you don't do


 11   when you talk to adolescents about obesity is use


 12   the word "obesity."  As I say, it is an art form


 13   and children are extremely interested in knowing


 14   how to live healthy lives, and they are very


 15   conscious of their bodies, their body weights and


 16   their physical appearance, and they very definitely


 17   want to be healthy.  But if you come at them with


 18   information that talks about obesity, it is a


 19   turnoff.  These are things that are sort of the


 20   subtleties of this issue that we have to get around


 21   and understand.


 22             [Slide]




  1             What research would be helpful for a


  2   facilitator to know about?  Again, this is the same


  3   as in the other aspect, to provide the best


  4   guidance to the agency on this subject.


  5             [Slide]


  6             What other questions should FDA be asking


  7   a facilitator to explore in order to help the


  8   agency develop effective educational strategies?


  9             [Slide]


 10             In view of the materials you have been


 11   provided, is there any other advice or information


 12   you believe is important to give FDA on this issue?


 13             [Slide]


 14             Let me finish by saying just two things


 15   here.  I have a couple of quotes.  One is from Dr.


 16   Crawford: "We're going back to basics, designing a


 17   comprehensive effort to attack obesity through an


 18   aggressive, science-based, consumer-friendly


 19   program with the simple message that 'Calories


 20   Count.'"  That really in a sentence summarizes what


 21   it is all about on that subject.


 22             [Slide]




  1             Our Secretary, Tommy Thompson:  "Counting


  2   calories is critical for people trying to achieve


  3   and maintain a healthy weight.  This new report


  4   highlights FDA's overall strategy for getting


  5   consumers accurate, helpful information that allows


  6   them to make wise food choices at home, at


  7   supermarkets and in restaurants.  Taking small


  8   steps to eat a more balanced diet and to stay


  9   physically active can go a long way to reversing


 10   the epidemic of obesity that harms far too many


 11   Americans."


 12             I think we are at a point where we have


 13   written the report and we have delivered the


 14   report.  The report has recommendations and we now


 15   want to move forward with those recommendations to


 16   take the next steps.  What I have described by way


 17   of third-party facilitated national dialogue on


 18   these two main issues about restaurants and


 19   pediatric obesity are concrete first steps that I


 20   think we can take beyond just delivering a report.


 21   We look forward to your feedback on these questions


 22   and your good guidance to the agency.  That is my




  1   presentation.  Thank you.


  2        Questions and Discussion with the Board/Presenters


  3             DR. SHINE:  Thank you very much, Dr.


  4   Rulis.  I know there are a couple of questions that


  5   we were going to come back to with our first two


  6   speakers, and we will do that at the end of this


  7   session, but I would like to focus over the next


  8   few minutes on the challenge from Dr. Rulis with


  9   regard to commenting on the charge to the


 10   facilitator.  I gather he is not asking us the


 11   answer to those questions.  He is asking us are


 12   those the right questions and are there other


 13   questions or other approaches that would be


 14   important for FDA to undertake.  We also have a


 15   written copy of these questions.  Jim, why don't


 16   you go ahead?


 17             DR. RIVIERE:  I just have one comment.


 18   Focus groups seems to be the primary mechanism that


 19   you are going to ask this facilitator to address


 20   these questions, and just that there be a lot of


 21   concern about the makeup of those focus groups.  It


 22   seems trivial, but even from personal experience




  1   with focus groups, people who will go to focus


  2   groups, there is a selection process in that area,


  3   especially for some of the questions on teens--and


  4   I still have two teenagers.  One has a problem in


  5   this area and the other one doesn't.  You know,


  6   same environment; obviously different genetics--but


  7   the point really is in looking at who would


  8   participate in this and how you would get them to


  9   participate because otherwise your results are


 10   going to be strongly biased to people who may not


 11   even have a problem to begin with.  And I agree, if


 12   you say it is an obesity focus group you are not


 13   going to get the right target population you want,


 14   but just to try to look at some clinical trial


 15   sampling protocols to make sure you have a


 16   representative group.


 17             DR. RULIS:  Thank you.  Let me just add in


 18   response, if I might, that in the course of our


 19   deliberations we did have the opportunity to do


 20   some focus groups and we did them, and they


 21   contributed to the report.  But we were all very


 22   much aware that, yes, indeed, they are not really




  1   research; they are focus groups, and that what


  2   needs to happen is research that has a much broader


  3   and deeper sort of foundation and a long-term


  4   lasting effect.  So, yes, thank you.  I think it is


  5   a very important point and we need to keep that


  6   very clearly in front of us.


  7             DR. SHINE:  Susan?


  8             DR. HARLANDER:  When you mentioned that


  9   you were going to get a third-party facilitator


 10   involved, I am assuming that that is going to go


 11   way beyond consumer-based focus groups.  My


 12   understanding is that that facilitator would also


 13   be engaging the other stakeholders, like the


 14   restaurant industry or the food industry--


 15             DR. RULIS:  Very definitely.


 16             DR. HARLANDER:  --and I think it is


 17   critically important to involve stakeholders


 18   because food companies and restaurants understand


 19   their consumer base and they do a tremendous amount


 20   of proprietary research internally that they might


 21   be quite willing to share with you under certain


 22   circumstances.  So, I think industry involvement is




  1   critical.


  2             Personally, I tend to believe that the


  3   market is going to sort itself out on this issue.


  4   You already see that certain restaurants, if they


  5   perceive that their consumers are interested in


  6   more healthy alternatives, are including them on


  7   the menu already.  So, you know, I think that they


  8   can bring a tremendous amount of knowledge to what


  9   you are trying to do.  I guess my understanding is


 10   we are going way beyond consumers and will involve


 11   the affected industry as well.  That is true?


 12             DR. RULIS:  Yes, thank you.


 13             DR. SHINE:  Susan, given your background


 14   in food science, what is your general reaction to


 15   the set of questions that have been raised?  Are


 16   these the right questions, do you think?


 17             DR. HARLANDER:  Well, there is one


 18   critical question that I would add.  I would agree


 19   with all the questions that you have but I think


 20   one key area is that all of this information that


 21   will be provided is not free, and nowhere in the


 22   research that I have reviewed prior to this do we




  1   ask consumers if they are willing to pay for


  2   additional information.  If we are going to expect


  3   the food industry to change their labels, we have


  4   to understand that that is not free.  You know, it


  5   costs money to make all those changes, particularly


  6   if analytical work is going to be required.  The


  7   same will be true for restaurants.  They are not


  8   typically giving that kind of information to


  9   consumers so either they are going to have to use


 10   some sort of software package that is going to


 11   predict this, which they haven't typically used in


 12   the past, or they are going to have to do


 13   analytical--they are going to have concerns about


 14   liability.


 15             So, I think one question I would add is if


 16   there are costs associated with that, are consumers


 17   willing to pay.  I just spoke with one gentleman


 18   and we talked about, you know, maybe consumers


 19   would be willing to pay more for a smaller bag of


 20   French fries than for a larger bag of French fries.


 21   If those costs were there, would that influence


 22   what consumers would buy?  Because I think that




  1   kind of information would be very helpful as you


  2   approach restaurants to try to get them involved.


  3   So, I think if there is a cost associated with


  4   this, we need to understand that.


  5             DR. SHINE:  Other comments?  Yes, John?


  6             DR. THOMAS:  I would like to make some


  7   comments with respect to focusing on our youngsters


  8   and the various inequities in school systems across


  9   the country.  Certainly, it seems to me, and I am


 10   generalizing now because I am sure some schools are


 11   much more advanced than others and maybe this is


 12   more detail than you are really searching for at


 13   this point in time, but establishing under the


 14   rubric of PTAs, for example, some sort of


 15   nutritional council where, in fact, they bring the


 16   PE teacher, the health educator, other dieticians,


 17   assuming that particular school board has access to


 18   that because I realize there are going to be some


 19   small schools that may not have those--I know, for


 20   example, a lot of schools have begun to put


 21   restrictions on school vending machines which


 22   heretofore was a major source of discretionary




  1   monies for the school principal where he or she


  2   could go out and buy books, or whatever, which


  3   otherwise was not funded by their particular


  4   budgets.


  5             Also, building into that overall concept


  6   some sort of notion of nutritional incentive.


  7   Weigh these kids at the beginning of the year and


  8   see what happens at the end of the year.  You know,


  9   give them a goal to shoot for.  Don't just talk


 10   about it on the first day and then forget about it.


 11             We can't change the busing system with


 12   respect to physical activities.  We all live in the


 13   suburbs now so that one is taken away from the


 14   pediatric cohort.


 15             Finally, I think there needs to be a


 16   reemphasis on individual sports in our school


 17   systems.  Team sports have obviously taken


 18   precedence but they need to have lifelong physical


 19   activities and we need to encourage them through


 20   the physical education departments and whatever


 21   structure they have to go forth with lifelong,


 22   single competition sports.  Nowadays you can't even




  1   get kids to run out to the ball field because it


  2   has to be organized.  There is no such thing as


  3   getting a group of youngsters just to play ball for


  4   the fun of it.  It has to be a lesson or it has to


  5   be a league.  Somehow we need to encourage tennis,


  6   golf and other things that they are going to do for


  7   the rest of their life.  Again, I am sure there are


  8   schools that are already doing this but it has to


  9   be a coordinated effort for these various skill


 10   sets.


 11             DR. SHINE:  Thank you.  Other comments?


 12   Yes, Cato?


 13             DR. LAURENCIN:  Well, I would like to echo


 14   some of the thoughts that were said earlier.  I


 15   think that a number of groups are already trying to


 16   do this; a number of large chains are already doing


 17   this.  My one comment is that I think the FDA can


 18   be very helpful in terms of young people by trying


 19   to keep it simple.  I went to one restaurant where


 20   the place mats actually had all the nutritional


 21   information for all the different foods that they


 22   had.  I have two doctorate degrees and I was just




  1   about able to get through it, so I think that a


  2   young person might have a difficult time getting


  3   through it.


  4             We are trying a pilot program at our


  5   university where we are labeling the foods in the


  6   vending machines with green, yellow and red.  The


  7   foods that are labeled red have actually five


  8   percent surcharge that goes to research.  So, these


  9   sorts of methodologies are where perhaps the FDA


 10   can be helpful in terms of being able to decide


 11   what is green, what is yellow and what is red and


 12   also, of course, the possibility of recommendations


 13   in terms of how we can disseminate this sort of


 14   information in terms of what the different levels


 15   are, and things like that.


 16             One, I think it is important to try and


 17   keep it simple in terms of actually trying to help


 18   young people.  Number two, we can even place some


 19   monetary incentives and make that a part of it, and


 20   I think it would be good.


 21             DR. SHINE:  Thank you.  Josephine?


 22             DR. GRIMA:  In recent years the public has




  1   been bombarded with information about low


  2   carbohydrate diets, and although this is not a


  3   trend that has been endorsed by the AMA or


  4   government associations, the fact of the matter is


  5   that that information is out there in the public.


  6   I think one of the important things to address is


  7   how much information is really the consumer taking


  8   in, and I think the facilitator has to use that in


  9   their plans in order to educate the public on this.


 10             DR. RULIS:  Yes, I will just respond


 11   briefly on the carbs issue.  The carbs issue is


 12   front and center right now.  It is on a lot of


 13   packages we see in the stores and we are well aware


 14   that this is an issue that is really crying out for


 15   some clarification.  As we have stated in our


 16   report, we are currently in possession of some


 17   petitions that are intending to try to clarify some


 18   of these statements on labels and we are working


 19   very hard.  Those of us who have spent many years


 20   at FDA, we relish the opportunity to beat our head


 21   against hard problems--


 22             [Laughter]




  1             --and this is a difficult one because, you


  2   know, what is a carb, first of all, and then how do


  3   you impart information in a way that is not


  4   misleading and, yet, doesn't impinge on people's


  5   right to say things under the First Amendment?


  6   These are difficult questions but we look forward


  7   to trying to solve them.


  8             DR. SHINE:  Susan?


  9             DR. HARLANDER:  I just have one reaction


 10   to what Cato brought up.  I think that there is a


 11   lot of concern about labeling foods as good foods


 12   or bad foods, and that you will get a lot more


 13   cooperation from the food industry and the


 14   restaurant industry if any food, whether it is a


 15   green dot, yellow dot or a red dot, can fit into a


 16   balanced diet, and it has a lot to do with how much


 17   you are going to consume of that.  But I think


 18   there is a lot of concern about is something going


 19   to be categorized as a bad food as a result of some


 20   of these efforts, and it might create some lack of


 21   willingness to cooperate.


 22             DR. SHINE:  Yes, Xavier?




  1             DR. PI-SUNYER:  I think you get around


  2   that by talking about total calories, and you get


  3   around the carbohydrate issue also by talking about


  4   total calories, which I think is what the FDA is


  5   trying to do.  I think the really important thing


  6   is how many calories people are eating in relation


  7   to how much exercise they are doing.


  8             I would just like to say a couple of


  9   things.  Number one is that I think it would be


 10   nice if the FDA would collaborate with other HHS


 11   agencies on these campaigns.  For instance, CDC is


 12   very much involved with the physical activity


 13   aspect of trying to educate the public, and it


 14   would seem to me that eventually, if and when the


 15   FDA goes out with an educational program for


 16   raising the consciousness of the American people or


 17   to raise the consciousness of the restaurants, or


 18   whatever, that there be kind of a concerted effort


 19   with agencies like the CDC which are working on the


 20   other side, which is the expenditure side.  That is


 21   number one.


 22             Number two, I think that the main emphasis




  1   really ought to be on prevention.  I agree with Dr.


  2   Swanson completely that weight loss is extremely


  3   difficult, and it is expensive, and it is hard to


  4   do and it is hard to maintain.  What I think the


  5   message needs to be for children and for adults is


  6   to control their weight.  The average American is


  7   gaining an enormous amount of weight every year and


  8   over a decade they are gaining between 10 and 20


  9   pounds.  So, what we want to do is to prevent that


 10   weight gain from age 21 or age 18 on, and I think


 11   that is where the focus really ought to be of the


 12   campaign.


 13             DR. SHINE:  Dr. Crawford is going to


 14   comment, but again, looking at the questions that


 15   you were asked, are these the right questions for a


 16   facilitator?  Are you comfortable with the


 17   direction that this is taking?


 18             DR. PI-SUNYER:  Well, I am comfortable


 19   with that direction.  I think we need to know more


 20   about behavior but, you know, the trouble is that


 21   we do know quite a bit about behavior already,


 22   particularly from other campaigns with tobacco and




  1   other substances of abuse, and I think changing


  2   behavior is very hard.  I am not sure that these


  3   focus groups are going to give you the answers


  4   totally that you are looking for.


  5             I do think talking to the focus groups,


  6   particularly about the labeling, is very important


  7   because clearly, as Cato says, you don't want to


  8   give them a label that they are not going to be


  9   able to read or that they are going to throw up


 10   their hands and say I don't understand this.  So, I


 11   think the whole label reading aspect of this focus


 12   group initiative is very good.


 13             DR. CRAWFORD:  Your question about


 14   coordination within HHS was a good one.  The way


 15   Secretary Thompson dealt with this as he moved this


 16   towards the top of his priority list was that, as I


 17   mentioned, about a year ago he caused NIH, CDC and


 18   FDA to put together these in-depth studies, headed


 19   up by working groups chaired by the deputies at


 20   each one of those organizations.  I was the one who


 21   chaired the FDA one.


 22             Then, one week about three months ago each




  1   of the agencies presented their findings to the


  2   public.  It was obesity week for Secretary Thompson


  3   and he had three separate and then one unified


  4   press conference.  At that point, the Department of


  5   Health and Human Services took over the public


  6   education initiative.  FDA's role will be to feed


  7   into that, as will the CDC's.  That initiative of


  8   education has begun with an ad council campaign.


  9   Then it will be followed up with some more in-depth


 10   approach as we attempt to reach all strata of


 11   American society.  The message will be refined.  It


 12   will be more sophisticated as it moves forward from


 13   the base, which is like a cartoon type presentation


 14   which is called sometimes the "body parts"


 15   presentation because in the most famous one of


 16   those ads someone is walking through a supermarket


 17   aisle and there is some protoplasm on the floor,


 18   and a little girl asks her parent what is that on


 19   the floor, and the parent responds it looks like


 20   someone lost their double chin from eating well.


 21             [Laughter]


 22             It is a very catchy campaign.  I am




  1   compelled to say so and that is how we get


  2   coordinated.


  3             DR. SHINE:  Let me just follow-up on this


  4   for a minute.  I think there is a real question


  5   here to understand the niche of the FDA in this


  6   area.  I think one needs to explore very carefully,


  7   not only in terms of the federal agencies but state


  8   health departments, medical associations and others


  9   who are confronting this problem at local


 10   communities.  Changing this with national publicity


 11   creates a certain kind of environment, if you will.


 12   But where the rubber hits the road is going to be


 13   concerted efforts in communities that will address


 14   all of the elements.  We have talked about


 15   restaurants and schools but what about company


 16   cafeterias and the whole question of whether, in


 17   fact, it is economically desirable to a company


 18   which has X amount of turnover to be paying Y


 19   amount of dollars in order to minimize the obesity


 20   that goes on in that company because it might help


 21   them save healthcare costs with diabetics and


 22   hypertensives, but that depends on turnover.




  1             So, the kinds of programs that we are


  2   talking about are going to be partnerships.  They


  3   are going to be efforts to get the media, to get


  4   the schools, to get industry to relate to this


  5   issue of everything from bike lanes to exercise or


  6   fitness programs in companies.


  7             My point is that I think the extent to


  8   which the facilitator can really hone in--the


  9   agency is famous for its capacity to analyze


 10   science and to find science-based information which


 11   could form the basis of all of these programs.


 12   Articulating that, modifying that, working on that


 13   so that it is part of these overall programs is


 14   going to be key.  Therefore, I would urge them to


 15   look fairly broadly as to what we are talking about


 16   and I think, again, I would not exclude state


 17   health departments.  I wouldn't exclude both urban


 18   and rural environments as places to understand what


 19   the niche is.


 20             I would also suggest to you that


 21   increasingly in 8th grade biology there is an


 22   interest of young people about their bodies, and so




  1   forth.  Anorexia-bulimia has been a major target


  2   for those educational programs.  The question is


  3   whether those educational programs could provide a


  4   balanced view of diet, exercise, and so forth, and


  5   is the FDA an ideal source of information packages


  6   and materials that could be used in public schools?


  7   With all due respect to USDA, I worry about the


  8   USDA's way of presenting that.  Perhaps between the


  9   two agencies one might be able to come up with


 10   material that would be part of the curriculum in


 11   terms of that.


 12             Finally, I want to emphasize, as I


 13   mentioned before about tobacco, that everything we


 14   have learned about changing behavior has to do with


 15   not just the information but changing the


 16   environment, whether it is because you pay more or


 17   whether because something is accessible or not.


 18   Therefore, when you talk about children, I happen


 19   to think that is where an enormous amount of the


 20   focus should be.  I think the public cares about


 21   their kids.  I think they will often do one thing


 22   and do something else for their kids.  So, as far




  1   as they are concerned, starting in kindergarten,


  2   the environment in which they are living will make


  3   an enormous difference as to what their lifetime


  4   habits are.  So, I don't think you can start too


  5   early.  Although I have focused on the 8th grade


  6   biology course, the fact is that if a second grader


  7   sees vending machines all around with high cal food


  8   or high fat food, they are going to assume that it


  9   is part of the environment in which they live.  So,


 10   I think the emphasis on pediatrics is extremely


 11   important but that one ought to think about it in


 12   terms of how and in what way you can use the data


 13   that you have to change the environment in terms of


 14   what is available to people.  Katherine?


 15             DR. SWANSON:  Kind of building on the


 16   notion that behavior is important, I personally


 17   think that your question related to how do you


 18   measure effectiveness is the most important one.


 19   If you go down the path of trying all of these


 20   different concepts and you don't have a way to


 21   measure behavior change--not just what people say


 22   they will do but what they will do--you really




  1   won't be able to target what is going to have the


  2   biggest impact.  So, I would make sure that that


  3   question might be thought of first with every


  4   strategy that you are looking at, how would we


  5   impact the magnitude of the change.


  6             Another thing to consider with regard to


  7   the restaurants, listing the calories I think is


  8   very interesting.  The segregation out of healthy


  9   choices is another.  Another option that would be


 10   very interesting to explore that would be


 11   applicable to the white tablecloth restaurants as


 12   well would be smaller portion sizes.  I mean, many


 13   of us who are on the road all the time and you go


 14   to the restaurant and you simply cannot eat all of


 15   the food that is put on your plate, and would you


 16   be able to pay not half as much because there are


 17   labor costs there, but offering multiple service


 18   sizes might be a very interesting thing to study


 19   because if you reduce it by half you have cut your


 20   calory intake in half.


 21             One more question that you might want to


 22   add is, is there a way that you can link the




  1   caloric intake piece to the caloric output piece in


  2   some kind of a message?


  3             DR. SHINE:  Thank you, Katherine.  I would


  4   suggest that I would like a facilitator to create a


  5   model for continuous quality improvement in this


  6   area.  What I mean by that is we don't know what


  7   works.  We don't know what will not work.  We need


  8   a concept that there is a lot of experimentation


  9   going on to learn from that what impact it has, and


 10   then constantly reassess how and in what way we are


 11   using our activity.  I think the notion is that it


 12   is for the long haul.  I think that looking at that


 13   in terms of socioeconomic status, ethnic groups,


 14   and so forth, is going to be pretty central


 15   because, in fact, they may behave very differently


 16   and it is not at all clear to me, once you get the


 17   data and put something in place, that it will work


 18   in the same way in a variety of settings.  So, I


 19   think that notion of what is the long-term model


 20   for constantly reassessing where one is and where


 21   do you get the data, how do you get the data, what


 22   are you trying to measure in order to make those




  1   decisions would be an important part of how to


  2   conceptualize this.


  3             Incidentally, we were talking at the break


  4   about differences in terms of environment and


  5   culture.  You might be interested to know that the


  6   Japanese, about a year or two ago, redid the


  7   height/weight tables for boys because the boys are


  8   getting so much bigger and putting on more weight.


  9   They are also getting higher cholesterol levels,


 10   incidentally.  But girls are not.  The culture in


 11   Japan is so focused on young women being thin that


 12   they have shown no change in the height/weight


 13   environment.  So, these cultural elements make an


 14   enormous difference in terms of how people behave.


 15   Other comments?


 16             DR. THOMAS:  Just a couple of follow-up


 17   points, and these are certainly not revelations but


 18   I would strongly urge as you look at behavioral


 19   profiles that you make every effort to get a


 20   quantifiable endpoint.  That is almost a


 21   contradiction when you are dealing with behavior,


 22   but as you go into this I think you really need to




  1   look at those endpoints.


  2             The other thing, I was struck by the


  3   simplicity of the color coding that Cato mentioned.


  4   While it has a downside and you can get into the


  5   good and bad foods, I think the general public