World Obesity Congress and Expo

Keynote address

by
Lester M. Crawford, D.V.M., Ph.D.
Acting Commissioner of the FDA

for
World Obesity Congress & Expo

July 12, 2004

This text contains Dr. Crawford's prepared remarks. It should be used with the understanding that some material may have been added or deleted during actual delivery.

Thank you, Jose (Caro, VP, Endocrine Research and Clinical Investigation, Eli Lilly & Co.) for the introduction, and good afternoon.

I am delighted to participate in this conference called to examine potential answers to a major public health concern affecting practically the entire world. It's a concern that's high on the health care agenda of countries on every continent -- an issue of growing seriousness and prominence not only among industrialized nations, but also in some parts of the Third World. In the United States, this issue commands the closest attention of the Department of Health and Human Services and, in particular, of the agency I have the honor to represent, the Food and Drug Administration.

I am talking, of course, about the epidemic of overweight and obesity, an unforeseen and unwelcome adverse effect of the proud achievement of our food producers and modern technology, which is the overflowing horn of plenty.

At the FDA, we are accountable for the safety and the wholesome nature of 80 percent of our national food supply -- practically everything we eat except for beef, poultry, and a few egg products. This responsibility, in addition to our general duty to protect and promote the public health, has placed our agency in the forefront of our government's efforts to bring the runaway excess-weight problem under control.

And a major problem it is: overweight and obesity affect about two out of every three Americans -- and, what is even more alarming, 15 percent of our children and adolescents. These extra pounds are ruinous to health by increasing the risks for a host of diseases that are inflating our nation's morbidity and mortality statistics. According to the most recent estimates, obesity is a causative factor in as many as 400,000 deaths each year, which makes it the second most devastating avoidable cause of premature death in United States after tobacco.

Moreover, while smoking is on the decline, overweight and obesity statistics are relentlessly rising, and threaten to erode the substantial gains in life expectancy and quality of life that have been won by modern medicine. While the resulting human suffering is the most dire aspect of this epidemic, its economic consequences accentuate the hardship. The costs of obesity-associated health care and lost productivity are currently estimated at $117 billion a year.

For us at the FDA, this ominous drift into disease and expense presents a tremendous challenge that -- although not at our doorsteps alone -- we know we must confront with all available powers and resources. Last August, we therefore appointed an expert Obesity Working Group and charged it with two basic tasks: exploring the critical dimensions of the excess-weight problem, and devising a plan how to address it.

The group's probe was a major undertaking. Our working group consisted of 17 FDA senior scientists and staffers who were backed by more than 40 specialists researching the various issues under study. We were briefed by experts from other government agencies; consulted with the public and academia; met with representatives of the packaged food and restaurant industries; and solicited and reviewed scores of expert comments on various aspects of the obesity epidemic.

We dug deep into scientific literature -- to give you one example, our report, which was released in March, includes 50 references to studies and professional articles dealing with nutrition labeling of packaged goods and in restaurants, which is just one of the eight key issues we examined. In addition to surveying what's known, we also identified knowledge gaps that need to be filled, and recommended areas for further biomedical and social sciences research.

We explored the effectiveness of obesity-related messages in the public and private sectors, and examined various education programs for promoting healthy nutrition. And we surveyed existing therapies for mitigating obesity.

What have we learned? The overriding lesson of our inquiry is that the epidemic has no single cause: rather, it is the confluence of numerous factors acting together over time. Ergo, our second key conclusion is that the epidemic will have no simple or speedy solution. Controlling obesity will be long-term process requiring coordinated and comprehensive efforts on many fronts.

One of the most surprising findings was that a large part of our population is not even aware that excessive weight is a health problem. Evidence reviewed by our group indicates that both adults and teenagers frequently misperceive their weight status, and that this misperception cuts across gender, socioeconomic status, age and ethnicity.

This is particularly true about individuals who regard themselves as overweight rather than obese. Recent focus group studies indicate that these men and women generally brush of the extra pounds as of minor significance, and therefore have little incentive to get rid of them. Raising the public's consciousness that excessive avoirs-du-pois are a serious health hazard is our foremost, urgent task.

Another big hurdle to be overcome is the inaccurate assessment by many consumers of their diets' implications for their health. For example, a survey of the U.S. Department of Agriculture has found that four out of ten people who cook at home have an exaggerated opinion of the nutritional quality of the meals they prepare. Other research has shown that many parents significantly underestimate how often their children snack between regular mealtimes. A large segment of our public appears to lack -- or even care about -- accurate information about their nutrition.

This was reflected in the disappointing effectiveness of the current food label, which shows how the major nutrients in each food package fit into a healthy daily diet of 2,000 or 2,500 calories. When it was first introduced, more than 10 years ago, fewer than 56 percent of Americans were overweight, and fewer than 23 percent were obese. It was then estimated that the implied dietary advice on the label would prevent many of the then-300,000 overweight-related deaths a year, and save up to $13 billion in health care costs in a decade.

Today, we know better.

These findings heightened the importance of another key aspect of the Obesity Working Group's agenda, which was to explore the ways of addressing the excess-weight phenomenon from another direction: by facilitating the development and marketing of safe and effective new therapies for obesity.

The concept of extreme body weight as illness is hardly new: already in the 5th century B.C., Hippocrates noted that "sudden death is more common in those who are naturally fat than in the lean," and in 1760, a Scottish physician named Flemyng wrote that "corpulency, when in an extraordinary degree, may be reckoned as a disease, as it in some measure obstructs the free exercise of the animal functions; and hath a tendency to shorten life, by paving the way to dangerous distempers."

By while many of these "distempers" -- which we now know range from cardiovascular hypertension and congestive heart failure to diabetes, stroke, osteoarthritis, and psychological disorders -- have been frequently and successfully addressed by pharmaceutical R&D, attempts to develop a remedy for the underlying condition have repeatedly failed to demonstrate adequate effectiveness and safety.

One of the earliest obesity therapeutics, first used in the 1880s, was thyroid extract. It induced weight loss by causing hyperthyroidism, itself adverse to health. Dinitrophenol, introduced in the 1930s, is a highly dangerous agent that causes cataracts and neuropathy and, even worse, all too often results in hyperthermia, metabolic collapse, and death. Amphetamines and their congeners, prescribed since the late 1930's, dominate the field of weight-control medicine, but have the down side of being potentially addictive, subject to abuse, and are not ideal in a population at risk for heart disease.

Over time, and particularly in recent years, the medical community has come to recognize that short-term measures to address obesity don't adequately reduce the long-term risks associated with excess weight. As we all now know and understand, obesity is a chronic condition associated with wide-ranging derangements of energy metabolism. Over the long term, that increases the risk for numerous serious and life-threatening diseases.

Based on this understanding, and following the recommendations of an advisory committee, our agency in 1996 issued a draft guidance that set the framework for the development of chronic-use drugs to treat obesity. The document called for long-term clinical trials of safety and efficacy, and set forth standards of effectiveness in the hope of fostering the development of a crop of chronic-use preventives and remedies that would ultimately reduce the disease risks of obesity.

Since then, our agency has approved three long-term treatments for weight control: dexfenfluramine, sibutramine and orlistat. Dexfenfluramine, which took the market by storm in a popular combination regimen with phentermine, was withdrawn within 18 months of approval after it was shown to be associated with valvulopathy. This was an effect not predicted by any of the premarket data, whether in animals or in patients. Sibutramine is an effective drug, but it causes increases in pulse and blood pressure in some individuals, and requires careful monitoring. Orlistat, like sibutramine, is modestly effective, though apparently very safe.

In sum, a highly effective drug-based treatment for overweight and obesity is, today, sorely lacking in the medical armamentarium. Available therapies are only modestly effective, by no means so in all treated patients, and have no lasting effect once the use of the drug is stopped, thus necessitating lifelong therapy in many individuals. We have no cure for obesity. Furthermore, there has never been a therapeutic class whose progress has been more vehemently buffeted by opposing desires for a true cure and concerns about drug risk -- concerns that are frequently accompanied by arguments that obesity should be addressed with behavior modification. Obesity therapeutics is an exceedingly difficult area in which to work.

At the same time, one of the most encouraging conclusions of our Working Group is that opportunities for safer and more effective obesity drugs abound, and that the future of weight-control therapies is potentially bright. The list of molecular targets and mechanistic approaches is long, and grows daily thanks to vigorous basic research in this field. We have good reasons to hope for the development of safe and effective single-drug therapies and combination regimens to assist people in achieving and maintaining healthy weight.

As part of our role in advancing this progress, FDA is planning a meeting of the Endocrine and Metabolic Advisory Committee in early September to open the agency's 1996 guidance for discussion. It is our intent to join experts from academia and industry in seeking the best path forward, and overcome the existing hurdles and barriers to the development of safe and effective treatment of obesity. I'll mention some of the basic topics that require exploration and debate:

First and foremost, we have no evidence from clinical trials that weight loss induced by any of the available obesity drugs reduces risk for long-term serious morbid -- such as cardiovascular disease -- and mortal consequences of the condition. It is of essence that plans to address this critical question be developed as soon as possible.
Reliance on weight loss alone as the measure of efficacy would seem to require large, long-term exposures for providing at least presumptive evidence of benefits outweighing risks. This is particularly true because historically, the benefits of these drugs have been on the average small, and by no means universal. This is clearly a barrier that must be discussed.
Given our limited armamentarium for obesity and the critical health effects and prevalence of the condition, we believe that head-to-head comparisons of new and existing treatments are critical for progress. It is, for example, disconcerting that the most frequently prescribed obesity drug in the U.S. today is phentermine. It is a drug that's approved for short term use, but clearly is prescribed chronically, and we have neither information on its long-term safety nor on its efficacy when compared to more recently approved chronic-use products.
In addition, we need to discuss the conduct of studies of combination therapies, and of trials to examine the safety and effectiveness of drug cycling. We need to address these issues for both new and previously approved therapies.

After six months of intensive consultations and research, our Obesity Working Group concluded that the stark reality of the obesity epidemic, and its deleterious consequences for health, constitute a call to action for the entire health-care community -- pharmaceutical industry, academia, health care professionals, as well as FDA and its sister public health agencies.

By that I don't mean to detract from the central role of sound diet and exercise, both of which must and will be the subject of a vigorous nation-wide educational campaign spearheaded by our government, involving scores of private organizations, and focused, primarily, on the young.

But all of us who participate in this conference, and our colleagues and peers who are not present, have also a crucial role to perform. The millions of Americans -- and people world-wide -- with excess weight problem urgently need the same type of option that exists for a myriad of other health conditions and ailments. We must join efforts to overcome the hurdles and gaps of knowledge that stand in the way, and provide them with safe and effective therapies.

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