Expansion of the Government Provision of Health Care and Individual Rights: Panacea or Pandora’s Box?

“The proposal that promoting and protecting human rights is inextricably linked to the challenge of promoting and protecting health derives in part from ecognition that health and human rights are complementary approaches to the central problem of defending and advancing human well-being.” Jonathan Mann.

The Patient Protection and Affordable Care Act will create a much needed expansion of government supported health programs which will improve access to health care for many Americans. However, under current jurisprudence, if the policy makers who craft these new programs fail to proceed with great caution, the expansion of the government provision of health care could come at a significant cost to individual rights. Our country sits at a crossroads with the choice to either proceed to promote the health and well-being of the population while promoting and protecting individual rights or to enhance public health at the expense of these rights.

The threat to individual rights which lurks within the expansion of government supported health care programs originates with the body of jurisprudence built around Rust v. Sullivan. In Rust, the Supreme Court upheld legislation that barred health care providers who accepted government funds from engaging in abortion counseling, referral and activities. The Court held that:

[t]he Government can, without violating the Constitution, selectively fund a program to encourage certain activities it believes to be in the public interest, without at the same time funding an alternative program, which seeks to deal with the problem in another way. A legislature’s decision not to subsidize the exercise of a fundamental right does not infringe the right. There is a basic difference between direct state interference with a protected activity and state encouragement of an alternative activity consonant with legislative policy.

This body of jurisprudence opens the door for programs like the one being pilot tested in West Virginia that I blogged on last week over at the Health Law Prof Blog. In early 2007, the federal government approved the West Virginia Pilot Project which provides health care for low-income, Medicaid beneficiaries. This program, and ones like it, is an attempt to respond to the ‘obesity crisis’ and the overall rise in health care costs. The West Virginia Pilot Project punishes those who do not join, and religiously adhere to, weight-loss or anti-smoking programs, or who otherwise fail to strictly comply with doctor's orders or to comply with government mandates. The punishment for this failure to conform is the denial of important medical services. A recent study of the program indicates that it is, in fact, negatively impacting access to health care. This type of paternalistic program violates the harm principle as it reaches out to broadly regulate the behavior of low-income individuals that is self-regarding; in other words, conduct that impacts only the individual. It is the first step on a slippery slope of potentially ever-expanding limitations on freedom of choice and individual rights, all in the name of public health.

Advances in genetic testing and in the science of pharmacogenomics that presage a new world of individualized medicine elevate the seriousness of this concern. Will this mean, for example, that a person with a particular genetic code must take a medication that pharmacogenomics dictates as the recommended treatment to ameliorate the condition and the long-term costs associated with treatment of the condition in order to qualify for future treatment of that medical condition? Taking this to the hypothetical extreme, what about a woman who has a BRACA-1 or 2 mutation with a very high probability of the future development of breast/ovarian cancer? Will she be forced to undergo surgical removal of her breasts and ovaries in her 20s in order to maintain her health care coverage and obtain treatment later in life if she contracts cancer? Is there a principled way to draw a line between what is acceptable regulation of self-regarding behavior with relation to health and what is not?

As we move forward to develop public health programs that deal with the rising cost of health care, it is hoped that we are able to design programs that seek to both promote public health while protecting individual rights. Cross posted at Health Law Prof Blog.

Psychological Interventions For Post Disaster Trauma

The world sighed a collective breath of relief when all 33 of the miners trapped in a Chilean mine for over two months were rescued this week. But the health risks for some of these minors may not be over. As I blogged previously here in the context of the serious emotional distress suffered by children affected by Hurricane Katrina, those who survive disasters are at significant risk of psychological problems such as post-traumatic-stress-disorder (PTSD), depression, anxiety and substance abuse.

It is imperative for those in the public health community to recognize that this risk can vary among individuals and that currently popular interventions may be ineffective and, more importantly, can actually cause harm in some cases. In a press release this week, The Association for Psychological Science cautions that post disaster interventions that attempt to deal with emotional distress should carefully focus on techniques with strong scientific evidence of effectiveness.

In an upcoming report on the psychological effects of disasters in Psychological Science in the Public Interest, a journal of the Association for Psychological Science, George A. Bonanno and colleagues note that
… '[f]ollowing disasters, the most common form of immediate psychological intervention is a single session known as critical incident stress debriefing (CISD). However, following a review of studies on the effectiveness of CISD, Bonanno and co-authors conclude that “multiple studies have shown that CISD is not only ineffective but, as suggested earlier, in some cases can actually be psychologically harmful.'

In a 2007 report in Perspectives on Psychological Science, a journal of the Association for Psychological Science, Scott O. Lilienfeld shows that a number of psychological therapies, including CISD, especially if forced upon survivors, may actually be harmful.

'The data on crisis debriefing suggest that imposing such interventions on individuals doesn’t work and may, paradoxically, increase risk for PTSD,' Lilienfeld says. 'If any of the miners want to talk to somebody to express their feelings, then by all means mental health professionals should be there to listen to them and support them. But for miners who would prefer not to talk much about the experience, it’s best to leave them alone and respect their own coping mechanisms.'

According to Bonanno and his co-authors, there are therapies that may be effective in helping survivors recover from disasters. Psychological first aid (PFA)—which, among other things, provides practical assistance and helps promote a sense of safety and calmness among survivors—is a promising approach. In addition, community-centered interventions—those that help maintain a sense of continuity, connectedness, and quality of community life—may be beneficial to survivors of disasters.

The Use of Best Management Practices to Reduce Nutrient Pollution in the Everglades Agricultural Area

It is only after my recent move to South Florida where I routinely drive on the Sawgrass Expressway that I appreciate how the wild beauty of the South Florida Everglades lives cheek to jowl with the buzz and press of busy city life.

William H. Owen captures this juxtaposition in a recent Earth Magazine article:

As the sun rises over the vast Florida Everglades, the endangered Florida panther quietly stalks a white-tailed deer in the tall grass. A raccoon fishes for its breakfast of crayfish. A small flock of rose-colored waterfowl flies overhead, a reminder of the vast flocks of wading birds that once called the Everglades home. A couple of otters roll around in the water nearby, keeping a watchful eye out for ubiquitous alligators. Manatees swim silently below the surface in Florida Bay, at the southern end of the Everglades ecosystem. Suddenly, a tractor engine revs to life as a farmer prepares to harvest his sugarcane, and the noise of commuters driving to work on the Sawgrass Expressway disturbs the calm. Such is life in the Everglades, where modern civilization meets wild in a vast subtropical wetland.

The Everglades is the largest subtropical wetland in the United States. It is an internationally recognized ecosystem that covers approximately two million acres in South Florida. Urban and agricultural development has endangered the biotic integrity of this ecosystem. One example of this development is the Everglades Agricultural Area (EAA). The EAA is one of several large portions of the original Everglades that was drained for commercial, agricultural and residential development. The EAA is approximately 700,000 acres and is 27% of the original Everglades. Drainage waters from the agricultural lands in the EAA contain nutrients, primarily phosphorous, from the use of fertilizers, herbicides and pesticides. This agricultural runoff flows downstream to areas that include the Everglades National Park. These excess nutrients have allowed nutrient loving plants like cattails to overrun the wetlands, displacing native species such as sawgrass.

In an article titled Reducing Nutrient Pollution in the Everglades Agricultural Area through Best Management Practices, Professor Alfred R. Light chronicles the social, legal and regulatory history of nutrient pollution reduction efforts in the EAA. Professor Light explains how the EAA farmers have recently used Best Management Practices to take the irrigation water with high phosphorous levels that flows into their fields and reduce those levels before allowing the runoff to drain downstream. Professor Light suggests that the successful use of Best Management Practices by EAA farmers will be a bellwether for other US farmers facing similar nutrient pollution problems. The abstract of the Article reads:

Some Florida farmers recently have been reducing the level of nutrient pollution discharged from their fields and entering sensitive Florida ecosystems from the level found in the irrigation water they use. They are doing this while continuing to operate their productive farms. Setting a water quality standard seems to have driven actual “real world” improvements in water quality in Florida, including development of the data and research needed to support those improvements. Mandatory BMPs seem to have worked in reducing phosphorus concentrations in water leaving the EAA. In fact, phosphorus concentrations in water leaving the EAA are about half of the concentrations in irrigation water entering the region. Other regions of the country with significant nutrient pollution thus may be looking to Florida to find out how farmers can be part of the solution rather than part of the problem. Florida’s BMP program in the EAA thus may be a bellwether for other states seeking to confront the challenges of nutrient pollution.

New Study Shows Serious Emotional Disturbances in Children Post Katrina

Mental health professionals have shown that there are serious emotional disturbances (SED) among children as a result of Hurricane Katrina. The Category 3 storm ravaged the Gulf Coast in August 2005. Characteristics of SED include inappropriate behavior, depression, hyperactivity, eating disorders, fears and phobias, and learning difficulties.

According to Virginia Tech News

A team made up of mental health professionals, emergency response experts, and researchers from several universities, including Virginia Tech, has published the results of a study that shows serious emotional disturbances among children who were affected by Hurricane Katrina. The Category 3 storm ravaged the Gulf Coast in August 2005.

The study, published in a recent issue of the Journal of the American Academy of Child and Adolescent Psychiatry, showed the estimated prevalence of serious emotional disturbances (SED) among residents of the affected areas was 14.9 percent. Of those, 9.3 percent of youths were believed to have SED that was directly attributable to Hurricane Katrina.

"Stress exposure was associated strongly with serious emotional disturbances," said Russell Jones, professor of psychology in the College of Science at Virginia Tech and member of the research team. "More than 20 percent of the youths with high stress exposure had hurricane-related SED."

The study found that youth who experienced death of loved one during the storm had the strongest association with SED. Exposure to physical adversity was the next strongest.
"The prevalence of SED among youths exposed to Hurricane Katrina remains high 18 to 27 months after the storm," Jones said. "This suggests a substantial need for mental health treatment resources in the hurricane-affected areas."

Katrina was the costliest hurricane in United States history as well as one of the five deadliest. Four years after the storm, nearly thousands of residents of Mississippi and Louisiana are still displaced from their homes.

U.S. Food Safety System In Serious Disrepair

More than 50% of food manufacturers are unaware of their legal obligation to provide the FDA with updated contact information that the FDA relies on to deal with emergencies, such as Salmonella or other forms of food contamination. According to a Report released yesterday by The Department of Health and Human Services, Office of Inspector General, federal auditors found that approximately 48% of surveyed manufacturers failed to provide the FDA with accurate contact information and approximately 25% provided no emergency contact information at all.

The GAO Report explains:

Each year, more than 300,000 Americans are hospitalized and 5,000 die after consuming contaminated foods and beverages. In the event of an outbreak of a foodborne illness, FDA is responsible for finding the source of the contamination and helping to remove the contaminated food products from the food supply chain. Recent outbreaks of foodborne illness involving peanut butter, peppers, and spinach have raised serious questions about FDA’s ability to protect the Nation’s food supply.

The Public Health Security and Bioterrorism Preparedness and Response Act of 2002 requires certain food facilities to register with FDA. The purpose of registration is to provide FDA with sufficient and reliable information about food facilities. This information enables FDA to quickly locate facilities during an outbreak of foodborne illness and to locate these facilities for inspection.

FDA requires each domestic food facility to provide information for the registry, including (1) contact information (i.e., name, full address, telephone number, and all trade names under which the facility conducts business); (2) contact information for the parent company; (3) contact information for the owner or operator of the facility; and (4) an emergency contact telephone number. If there is a change in a facility’s information, such as a new name or address, the facility must provide FDA with the updated information within 60 days. The information provided by facilities is stored in a database called the FDA Unified Registration and Listing System .....

Hat tip: Bill Marler at Marler Blog.

Biodiversity Loss Can Increase Infectious Diseases in Humans

Queensland's Daintree Rainforest, said to be 135 million yeras old, containing more rare and endangered plant and animal species than any other area

Fifty years ago, improved public health measures, the development of antibiotics, better vaccines, insecticides and advancements in surveillance resulted in a decline of infectious disease. However, an upturn in infectious diseases around the world, both emergence and reemergence, has been apparent since the late twentieth century. This increase marks the fourth major alteration in human-microbe relationships since the introduction of agriculture over 10,000 years ago.

This “epidemiologic transition” has triggered the development of new infectious diseases. Approximately 30 new diseases have been identified and old diseases have reemerged with a vengeance, like tuberculosis, malaria and cholera. These new diseases include human immunodeficiency virus/acquired immune deficiency syndrome (AIDS), Legionnaires’ disease, bovine spongiform encephalopathy (BSE)/variant Creutzfeldt-Jakob disease (vCJD), hepatitis C, Nipah virus, new hemorrhagic fevers as well as severe acute respiratory syndrome (SARS) and avian influenza.

Various changes in human ecology have contributed to this new era of infectious disease:

∙ rural-to-urban migration resulting in high density peri-urban slums;
∙ increasing long-distance mobility and trade;
∙ the social disruption of war and conflict;
∙ changes in personal behavior; and,
∙ the use and misuse of medical technology (e.g. the creation of drug resistant microbes).

Weiss, R., McMichael, A.J., Social and Environmental Risk Factors In The Emergence of Infectious Disease, 10 Nature Med. Supp. 570 (December, 2004).

Recently, more attention has been paid to the role of human-induced global changes in the increase in infectious disease, including widespread forest clearance and climate change. In a newly released study, “Biodiversity Loss Affects Global Disease Ecology,” which will be appearing in the December 2009 issue of BioScience, the authors review and combine a broad group of studies addressing this issue and conclude that there is an association between the current epidemiologic transition and biodiversity change, decline and extinction. As reported in ScienceDaily

‘Habitat destruction and biodiversity loss,’ -- driven by the replacement of local species by exotic ones, deforestation, global transportation, encroaching cities, and other environmental changes – ‘can increase the incidence and distribution of infectious diseases in humans,’ write University of Vermont biologist Joe Roman, EPA scientist Montira Pongsiri, and seven co-authors in BioScience.

According to ScienceDaily, Roman explains that "people have been working on this in individual diseases but no one has put all the studies together to compare them."

In 2006, he and Pongsiri gathered a group of scientists and policy analysts with expertise in a range of the new diseases being observed -- including West Nile virus as well as malaria, the African parasitic disease schistosomiasis, hantavirus pulmonary syndrome, and several others. From that meeting, the forthcoming BioScience study developed.

'We've reviewed all those studies and show that emergence or reemergence of many diseases is related to loss of biodiversity,’ says Pongsiri. 'We've taken a broad look at this problem to say that it's not just case-study specific. Something is happening at a global scale.’

‘We're not saying that biodiversity loss is the primary driver for all of these emerging diseases,’ says Roman, ‘but it appears to be playing an important role.

'We're trying to make the case that all of these environmental changes we're making, because they are anthropogenic, can be managed, can be controlled,’ says Pongsiri. ‘We may be able to actually reduce or prevent these diseases by managing for biodiversity from the genetic level to the habitat level.’

This new study is part of growing body of work in an area being referred to as Eco-epidemiology. This relatively new field of study brings epidemiology and ecology together to examine the relationship between biodiversity and public health. Among other issues, Eco-epidemiologists examine disease prevention in terms of habitat structure, promoting genetic diversity in non-human species and the protection of animal predators as ecosystem regulators.

A Broad Challenge to the FDA's Regulations: Botox Manufacturer Sues Asserting First Amendment Protection for Off Label Drug Claims

In a move that could undermine the FDA's premarket approval process for all health care products, the maker of Botox has filed a legal action against the government claiming first amendment protection for the distribution of “truthful, relevant information” to doctors regarding off-label uses of its drugs.

As Natasha Singer of the New York Times reports:

The Food and Drug Administration approves medicines for specific therapeutic indications. Once a drug is approved for a specific use, doctors are then free to use their medical judgment to prescribe the drugs for other unapproved, or off-label, uses. Manufacturers, however, are prohibited from promoting off-label uses to medical providers or advertising such uses directly to the public.

Botox, an injectable drug that can temporarily reduce muscle or gland activity, is approved in the United States to treat crossed eyes, eyelid spasms, excessive sweating, severe neck contortions and wrinkles. But many doctors use the drug for unapproved indications like facial spasms, vocal cord problems and migraine headaches. *** ‘If you could get a drug approved for one narrow use and then market it for everything else, there would be no incentive or motivation for a company to prepare data to ensure that it meets the standard for safety and efficacy,’ said Marc J. Scheineson, a lawyer specializing in food and drug regulation at Alston & Bird in Washington.

It appears that the Botox suit is claiming free speech protections that are similar to those that are currently provided for dietary supplements under the questionable decision of Pearson and Shaw v. Shalala, 1999 U.S. App. LEXIS 464 (Jan. 15, 1999). However, Pearson can be distinguished as dietary supplements are targeted to healthy portions of the population to help maintain or enhance health. Drugs are marketed to unhealthy, vulnerable portions of the population claim to aid in an individual’s struggle to return to normal health. This difference should be outcome determinative in the Botox case.

What the manufacturer of Botox wants to achieve is the ability for drug manufacturers to once again promote drugs while there is scientific uncertainty over their safety and effectiveness. It is taking the first step toward this goal by claiming this free speech in the context of communication to physicians. While the debate starts over this question, it will be prudent to recall the lessons taught by the Thalidomide case which occurred prior to the 1962 Drug Amendments and involved the distribution of drug to thousands of patients by doctors while there was still scientific uncertainty over its safety:

Thalidomide was widely distributed in Germany, Japan and the United Kingdom for sedative purposes and for the treatment of nausea in pregnancy for several years. In 1960, William S. Merrell Company, the manufacturer of the American version of Thalidomide, Kevadon, applied for FDA approval. However, it was clear to Dr. Frances Kelsey, one of the FDA officers examining the application, that the drug had not been adequately tested for safety before distribution. In spite of pressure to approve the drug placed by the manufacturer on both the FDA and Dr. Kelsey individually, Dr. Kelsey insisted that the drug needed additional testing to prove safety before FDA approval could be granted. In 1961, Dr.Kelsey learned of a possible connection between nerve damage in adults and Thalidomide. [These babies were born with phocomelia, which is a Greek word thatcombines the words ‘seal’ and ‘limb’ … where the long bones of the infants’ arms had almost completely failed to grow; their arms were so short that their hands extended almost directly from their shoulders. Their legs were less affected but showed signs of a similar distortion of growth . . . .”]. She requested that Merrell provide studies on the use of its Thalidomide product on pregnant women. In 1962, it was discovered that Thalidomide was causing serious birth defects in children. While the application for Thalidomide was pending for FDA approval,hundreds of severely deformed babies were being born in Germany. [Worldwide, it is estimated that 8,000 severely deformed babies were born because of thalidomide].Without the FDA’s knowledge, Thalidomide had already been provided to 20,000 patients in the United States as part of an 'investigational study.' Slaying the Hydra.

Part Three: The Relationship Between the Level of Regulation under the FDCA and the Health Status of a Product’s Targeted Population

An Introduction to the History of Quack Medicine

In the late nineteenth and early twentieth centuries there was a remarkable growth in the marketing of sham products to treat and cure disease.

At that time, the rate at which quack medicines were being introduced into the market far outpaced the development of the science necessary to establish the efficacy and identify the risks associated with each new product. This scientific lag time created a period when there was an information void that
predatory commercial interests were quick to use to their advantage. As the FDA carried the burden of proof to show that a product did not work or was unsafe in order to remove the product from the market, during this lag time predatory commercial interests were able to profit from scientific uncertainty to the detriment of public health.

During this long period in U.S. history, the curative claims of the predatory sham medicine salesmen were limited only by the gullibility of their targets. In many cases, the degree of gullibility was proportional to the level of desperation of the individual for a cure. The more dire the condition, the more vulnerable an individual was to the ‘flim flam’ of the greedy snake oil salesman. And the more dire the condition, the greater the degree of harm when the sham medicine did not work, causing injury over and above the original illness and/or causing a delay in seeking effective medical treatment. Thus, this lag time between initial marketing of a sham product and the development of the science necessary to resolve uncertainties over the new product’s safety and effectiveness was very costly in terms of human suffering and loss of life. Slaying the Hydra: The History of Quack Medicines

In 1962, after a series of highly publicized public health crises, legislation was passed to close this ‘space between’ created by scientific uncertainty by switching the burden of proof for safety and effectiveness from the FDA and onto product manufacturers.

As more fully discussed in the next entries in this series,

it was not until 1962 that legislation was passed that required manufacturers to obtain premarket approval for new drugs from the FDA by producing “substantial evidence” that the product is both safe and effective for its intended use. The Drug Amendments of 1962 allowed the FDA to make the transition
from its former inefficient and costly police role of enforcing specific statutory prohibitions by removing adulterated and misbranded products from the market, to its current gatekeeper role of preventing those products from entering the market in the first place. Thus, from 1962 until 1994, manufacturers were no longer able to ‘play in the grey’ and take commercial advantage of the scientific uncertainty over the safety and effectiveness of a product to the detriment of public health.

The legislative history of the FDCA makes it clear that Congress also intended that weight loss products fall into the same regulatory category as drugs and devices specifically to deal with predatory profiteering by product manufacturers that targeted a vulnerable population of those who were overweight or obese. In the legislative record, members of Congress expressed their intent to deal with the massive number of “worthless” products being marketed for weight loss at the time. Id.

Thus, prior to the passage of The Dietary Supplement Health Education Act (“DSHEA”) and the Nutritional Labeling Education Act (“NLEA”), the FDCA appears to have required that manufacturers of weight loss supplements obtain premarket approval by establishing the safety and effectiveness of their products before distributing them.

However, the passage of DSHEA in 1994 has confused this situation. To date, it appears that DSHEA is being interpreted to shift the burden of proof back onto the FDA with relation to dietary supplements marketed to both healthy populations and vulnerable, unhealthy populations.

With this over broad interpretation, predatory commercial interests are again being allowed to exploit scientific uncertainty. The door has now been re-opened to the same deceptive advertising that ran rampant in the late nineteenth and early twentieth centuries.

And unfortunately, tens of millions of vulnerable and desperate individuals who are overweight and at grave risk of developing a serious, chronic disease are being lured into this predatory playground. The United States has now come full circle and returned to the era of the snake oil salesman. The very public health problem that the FDCA was originally promulgated to deal with, fraudulent and deceptive products that put the nation’s health at risk, has reared its ugly head once again. Id.

The next blog post in this series delves into more details regarding the history of the quack medicines to give additional perspective to the relationship between the FDCA, the FDA and predatory commercial interests.

Post Two of a Series: The Relationship Between the Level of Regulation under the FDCA and the Health Status of a Product’s Targeted Population

The first post of this series began by asking whether functional foods should be regulated as drugs if they claim to treat abnormal health conditions. For example, was it appropriate for the FDA to characterize Cheerios as a drug as a result of its advertising claim that “you can Lower Your Cholesterol 4% in 6 weeks?” An abnormally high cholesterol level is a serious risk factor for disease and those with high cholesterol levels are in an abnormal state of health. By virtue of its claims to help this group of unhealthy consumers with their struggle to return to a normal state of health, should the manufacturer of Cheerios be required to undergo the FDA's premarket approval process to show that eating Cheerios is effective in lowering cholesterol as claimed?

The answer to this question may become more apparent by looking at another category of products that claim to help unhealthy people return to a normal health status – weight loss products.

The Obesity Crisis and Weight Loss Products

The United States’ obesity crisis is gaining momentum. In only fifteen years, eighty percent of Americans will be either overweight or obese. Being overweight or obese places an individual at a significant risk for developing hypertension, Type II diabetes, heart disease, stroke and cancer.

Conservative estimates predict that the health care costs associated with this epidemic will reach $956.9 billion in the 2020s. One of every six dollars spent on health care will be associated with the conditions of being overweight and obese. Significantly, for the first time in over a century, children and young adults will have a shorter life expectancy than their parents.

"This obesity epidemic has been matched by a rapid growth in the weight loss supplement industry. Overweight consumers desperate to lose weight are being lured by ‘magic bullet’ claims into purchasing ‘quick-fix’ weight loss supplements in order to lose weight and decrease their risk for disease. As the result of prodigious marketing campaigns, many adults and adolescents ... are turning to weight loss supplements as an alternative to diet modification and exercise.

Advertisements for the ‘quick-fix’ product that works to melt off pounds without diet or exercise, some even while you sleep, are everywhere. Enforma Natural Products, Inc. ran an infomercial marketing its product Exercise in A Bottle claiming it “helps your body burn more calories while you’re just standing or sitting around doing nothing – even while you are sleeping” and “[y]ou can enjoy all those delicious foods like fried chicken, pizza, cheeseburgers, even butter and sour cream, and stop worrying about the weight.” The manufacturer of a similar product called Maxiline advertised heavily by taking out full-page newspaper advertisements stating “[s]leep … and lose weight in just a few nights … you eat whatever you want.” The advertisement stated that the product worked because “the body’s fat cannot defend itself from attack while asleep.”

Commercials on television and radio, lengthy infomercials, magazine advertisements, mass mailings of brochures and Amway and “Avon-Calling” type visits from friends and neighbors hawking miracle potions for magical weight loss flood the American consciousness. In 2000, the sale of weight loss supplements in the United States reached $4.7 billion, with a projected increase of ten to twenty percent annually.

In the book Through the Looking Glass, Alice said, “[o]ne can’t believe impossible things.” The White Queen answered: “I daresay you haven’t had much practice . . . . When I was your age . . . I’ve believed as many as six impossible things before breakfast.”

Like Alice, for many, the impossible weight loss claims made by the current breed of snake oil salesmen defy credibility. However, viewed in context, these beliefs are more understandable. Many of these consumers, and, shockingly, their physicians, incorrectly believe that the FDA requires premarket testing to establish that these weight loss supplements are both safe and effective. In fact, the FDA does not require that these products undergo clinical testing for safety or efficacy prior to being placed on the market. This vast market exists in spite of the fact that there is little to no evidence that most of these products actually work. To the contrary, there is growing evidence that many are ineffective and unsafe.

In 2002, the FTC issued a report that fifty-five percent of the claims made within advertisements of over-the-counter weight loss products were either false or misleading. According to the FTC, more consumers are defrauded by weight loss products than any other product it has examined." Slaying the Hydra: The History of Quack Medicines

Why isn’t the FDA using its premarket approval authority to keep these sham products from entering the market in the first place? Not surprisingly, the weight loss supplement industry is marketing its products as dietary supplements and is claiming the safe haven protections from FDA regulation offered under the Dietary Supplement Health Education Act (“DSHEA”) and the National Labeling Education Act of 1990 (“NLEA”). What is surprising is that the FDA appears to agree. Are the weight loss supplement industry and the FDA correct?

The next several posts in this series will examine the history of the relationship between the FDCA, the FDA and predatory commercial interests and will ask whether there are lessons from the past that can assist in the analysis of current regulatory issues involving food, functional food and dietary supplements. If so, do these lessons also offer insights into the regulation of nanotechnology used in consumer products for direct and indirect human consumption — including food (directly and through the food production process), food supplements, cosmetics and sunscreens?

Post 1 in Series: The Relationship Between the Level of Government Regulation under the FDCA and the Health Status of a Product’s Targeted Population

Cheerios -- a Drug?

This past May, the FDA issued a warning letter to General Mills stating that the claim on Cheerios cereal that “you can Lower Your Cholesterol 4% in 6 weeks” turned the Cheerios from a food into an illegally marketed drug. When bloggers heard the news, posts ran from scolding the FDA to “grow-up,” to those which lauded the FDA’s action.

Who is correct? Is targeting a cereal one of those cases where, as one blogger suggested, the FDA has its priorities wrong? A look at one recent food trend may help answer this question.

By making its cholesterol lowering claims, Cheerios is entering the growing market for functional foods. In 2008, functional foods -- which are defined as foods that claim to have health benefits over and above the delivery of nutrients -– were a $30.7 billion dollar market. This market is predicted to grow by 40% over the next several years.

Examples include: probiotics in salsa and ketchup; omega-3 fatty acids in orange juice, eggs and peanut butter; pasta enriched with calcium; heart healthy ginger ale infused with green tea; ‘energy’ drinks with amino acids for joint health. The list goes on and on. One never knows what might pop up in a favorite food.

And now a new category of functional foods is cropping up which industry is calling cosmeceuticals -– foods that are being marketed to enhance appearance. (A bit confusing because that term is commonly used to describe drugs that are being marketed as cosmetics. Perhaps cosmefood would be better?). One example of a cosmeceutical for skin beauty is a product on the market that consists of marshmallows infused with allegedly skin-boosting collagen.

Fortified foods are not new. Iodine has been added to salt since 1924 to reduce the incidence of goiter. Grains have been fortified with niacin, thiamin, riboflavin and iron since 1943, a public health move that almost eliminated brain/skin degenerating pellagra within a decade. However, present day functional foods are flooding onto the market before the science exists on the effectiveness of many of their associated health claims.

Where should the FDA draw the line on regulation? Should the level of product regulation be linked with the health status of the product’s targeted population? While not stated explicitly, it appears that this is the strategy that the FDCA has followed since its inception. See Van Tassel, K., Slaying the Hydra: The History of Quack Medicine, The Obesity Epidemic and the FDA's Battle to Regulate Dietary Supplements, 6 Indiana Health L. J. 203-251 (2009).

Traditionally, the greatest amount of regulatory protection under the Food Drug & Cosmetic Act (“FDCA”) has been applied when products are targeted at vulnerable, unhealthy populations and claim to aid in an individual’s struggle to return to normal health. Examples of products that fall into this category by making health remedy or recovery claims include drugs and devices. For these products, the modern FDCA establishes a premarket enforcement process that places the majority of the cost and burden on the product manufacturer to establish safety and efficacy through the clinical trial process prior to distribution to the public. Without premarket approval from the FDA, these products will be deemed both adulterated and misbranded as a matter of law.

Conversely, the FDCA requires less regulatory protection when products are targeted to healthy populations to maintain or improve a normal state of health. Examples of products that fall into this category are traditional foods, and (until recently) a very limited number of functional foods and (once again, until recently) a similarly narrow category of dietary supplements. For these products, the FDA carries the burden of removing an unsafe or ineffective product by proving that it is adulterated or misbranded.

Currently, far too many functional foods and dietary supplements are being marketed to the unhealthy and vulnerable by making health recovery or remedy claims without demonstrating through premarket approval that their products are both safe and effective. It appears that Cheerios is just one product of many that are making these claims.

An abnormally high cholesterol level is a serious risk factor for disease and those with high cholesterol levels are in an abnormal state of health. Cheerios is claiming to help this group of unhealthy consumers with their struggle to return to a normal state of health. As one commentator remarked, it is possible “that some people with high cholesterol will see eating breakfast as a clinical treatment, perhaps even offsetting a more pressing need to cut back on French fries.” Consequently, by sending its warning letter to Cheerios, it appears that the FDA is heading down the right path.

The merits of the FDA’s position on Cheerios specifically, and functional foods more generally, may become more apparent by looking at another category of products that claim to help unhealthy people return to a normal health status -– weight loss products.

The next in this series of blog posts will provide a general introduction of the current problems with the claims being made by weight loss products, particularly in the context of the obesity crisis. The focus on the example of weight loss products will provide a structure for the following posts which will take a look back through the history of the relationship between the FDCA, the FDA and predatory commercial interests. Through this exercise, regulatory patterns will be identified that appear to link the level of product regulation with the health status of the product’s targeted population.

The goal of this series is to take lessons from the past and apply them to assist in the analysis of current regulatory issues involving food, functional food and dietary supplements. This first series will provide the ground work for the second series which will delve into the use of nanaotechnology in consumer products for direct and indirect human consumption -- including food (directly and through the food production process), food supplements, cosmetics and sunscreens.

— KVT

FDA Hearings On Restricting Salt: Should Health Advocates' Demands for Government Restrictions On Salt Be Taken Cum Grano Salis?

The FDA held public hearings this week over the GRAS (generally regarded as safe) status of salt. The hearings are in response to health advocates who argue that salt should be treated as a food additive. This would allow the FDA to set limits on the amount of salt that could be added to foods. In light of the role that salt and sodium play in the development of high blood pressure and subsequent heart disease, those of us who work in the public health arena may be quick to jump on this bandwagon. But is government regulation that limits consumer choice the proper answer in this case? If so, what does this mean for other GRAS ingredients such as sugar and caffeine?

The FDA’s regulatory strategy for food and food additives looks like this:

1. If the product is a traditional food (example, apples, wheat, corn), it existed before national food safety laws were passed and is presumed to be safe for human consumption based on extensive use and experience. Premarket testing of these traditional foods is not required. If the food product is deemed unsafe for human consumption, the FDA will use its seizure and injunctive powers to remove the product from the market.

2. If the product is a food additive, premarket testing for safety is required.

a. A "food additive" is a substance that becomes a component of food or affects the characteristics of food, unless the substance is generally regarded as safe (GRAS).

i. A substance is considered to be GRAS if there is a general consensus among informed experts that a substance is safe for human consumption; or, if the substance was used in food prior to 1958, it is deemed safe by virtue of common experience. Examples are salt, sugar and caffeine.

b. If a substance added to food is considered to be GRAS, it will not be regulated as a food additive and will not require premarket approval.

3. Once a food additive has been evaluated by the FDA and is considered safe and effective at certain levels, it is placed on a monograph and can be used as an ingredient in any food product, but only at the levels or in the amounts that are considered safe by the FDA for human consumption.

So if salt loses its GRAS status and is designated a food additive, the FDA can set limits on the amounts that food processors can add to food. This means that the salt content of many foods will be slashed, with a resulting impact on flavor. And consumers will no longer have the choice to eat foods that are bad for their health based on salt content.

Thoreau stated that if he was sure that " ... a man was coming to my house with the conscious design of doing me good, I should run for my life ...."

In his essay Persuasion and Coercion for Health: Ethical Issues in Government Efforts to Change Life-Styles, 56 Health and Society, 303-38 (1978) [reprinted in Rolf Sartorius, Paternalism (U. Of Minn. Press 1983)], Daniel Wickler gives some excellent guidance on when governmental interference with individual life-style choices is justified ... and when it is not.

Professor Wickler gives two reasons why our society values autonomy of decision making: first, because we believe we are the best judges of what is good for us and, second, because the right to make the choice is a good in and of itself. This is translated into our common moral concept of a right of non-interference so long as one does not adversely affect the interests of others.

One view is that an individual’s choice of what to eat or not is self-regarding behavior (does not harm third parties). When a choice is self-regarding, it should be protected from interference from others, even if the decision is unwise.

It is true that there may be situations where we lose the capacity for competent self-direction. Then, as Ulysses did when he approached the sirens, we rely on others to protect us from harming ourselves. This is the basis for guardianship of children and the mentally disabled where the guardian makes the rational choices that would have been made if the individual’s autonomy were not compromised by mental disability.

When a consumer chooses a food with a high salt content (think of french fries that are usually loaded with salt) is this a situation of free and voluntary risk taking, or behavior that is not under the consumer’s control? Or could this be a situation where consumers lack the capacity to make an informed choice?

Unlike the situation with nicotine and its addictive properties where health advocates argue that the choice to smoke is not voluntary, health advocates’ position with regard to salt intake is that consumers lack the capacity to make a wise and rational decision because consumers are not well enough informed.

Does this rationale support the intervention of the government to take the choice to consume salty foods away from competent adults? If it is true and there is a capacity problem based on ignorance, isn’t the solution education?

While regulation to limit the use of salt blocks the harm, education corrects the disability and restores the choice and, therefore, autonomy. Based on the strong value that our society places on freedom of choice, should regulators be obligated to use the less restrictive choice of education, if they can?

Phillus Aureolus Theophrastus Bombastus von Hohenheim (1493-1541), a.k.a. Paracelsus, is well-known for the phrase Alle Ding' sind Gift und nichts ohn' Gift; allein die Dosis macht, dass ein Ding kein Gift ist. It translates as All things are poison and nothing is without poison, only the dose permits something not to be poisonous. Now, this phrase is commonly shortened to "the dose makes the poison."

Finally, issues surrounding life style choices raise the subjectivity of the notion of harm. Professor Wickler explains:

The same experience may be seen as as harmful by one person and as beneficial by another: or, even more common, the goodness (or badness) of a given eventuality may be rated very differently by different persons. Although we as individuals are often critical of the importance placed on certain events by others, we nevertheless hesitate to claim special authority in such matters. Most of us subscribe to a pluralistic ethic, for better or worse, that has a central tenant that there are multiple, distinct, but equally valid concepts of what is good and what is the good life. It follows that we must use our personal preferences and tastes to determine whether our health related practices are detrimental.

If the FDA decides to revoke the GRAS status of salt, what does that mean for sugar, which is equally, if not more, harmful? And there are multiple studies that demonstrate that caffeine in excess has significant health effects. What could this mean for those of us who live for that morning cup of coffee or tea?

For those who love salt, adding an extra dash with a personal salt shaker provides a partial remedy. But for those of us who love coffee and tea, finding a way to exercise personal choice could be a bit harder.

When it comes down to an individual life style choices, should the FDA take the views of health advocates cum grano salis? After all, any substance in excess can become a poison.

Will the FDA Bar The Door When Stem Cells Produced From Therapeutic Cloning Come Knocking?

Semos (named after the god in Planet of the Apes) is the rhesus monkey who donated the skin cells used in the therapeutic cloning study.

David Cyranoski summarizes two exciting new studies in his article "Race to Mimic Human Embryonic Stem Cells:"

Two much-anticipated scientific firsts announced this week bring the dream of regenerative medicine a step closer. The production of cloned primate embryonic stem cells and the reprogramming of adult human cells both represent important milestones in the quest to produce 'pluripotent' cells, which can develop into almost any of the body's roughly 200 cell types. Human embryonic stem cells have this property, and those used in research are usually extracted from leftover embryos created during in vitro fertilization. But researchers want to create pluripotent cells that are genetically matched to individual patients. Such cells could then be transplanted to treat disorders such as Parkinson's disease and diabetes, or be used by researchers to model disease progression. Cloning offers one way to create these cells. This week, a team led by Shoukhrat Mitalipov of Oregon Health & Science University in Beaverton report the first creation of embryonic stem cells from cloned monkey embryos .... Until now, cloned embryonic stem cells had been created only in mice.

***

But there is another promising route to creating pluripotent cells that does not require eggs or the controversial destruction of embryos. On Tuesday, Shinya Yamanaka of the University of Kyoto in Japan reported that his team had created pluripotent cells from human skin cells and, on the same day, a team of researchers led by James Thomson at the University of Wisconsin, Madison, reported the same. Yamanaka's work builds on his exciting discovery last year that introducing four transcription factors into mouse skin cells 'reprogrammed' the cells into an embryo-like state. Early this summer, Yamanaka and two other groups reported using the same four factors to create cells that seemed to be indistinguishable from embryonic stem cells.

Since the results of these studies were announced, the news is replete with stories covering the ethical issues that swirl around stem cell technologies and the promises that they hold for the treatment of a broad range of medical conditions. Another interesting question that is little discussed but always lurks behind these new advancements is how the FDA will deal with these innovative technologies. Will the method that is used to generate the stem cell technology make a difference to the FDA’s approval of human clinical trials?

The FDA’s new regulatory structure put in place to capture jurisdiction over new technologies like stem cells generally tracks like this:

1. Tissues that are only "minimally manipulated" and are intended for "homologous use" are covered under the FDA’s "good tissue practice" regulations 21 C.F.R. Part 1271 promulgated under Section 361 of the Public Health Service Act authorizing regulation to prevent the spread of communicable diseases. Minimally manipulated tissues will not be considered drugs or devices and will not be subject to the pre-market approval process.

a. "Homologous use" is the "replacement or supplementation of a recipients cells or tissues with a HCT/P [human cells, tissues and cellular and tissue based products] that performs the same basic function or functions in the recipient as in the donor." 21 C.F.R. 1271.3(c).

b. "Minimal manipulation" with respect to cells and nonstructural tissues is defined as "processing that does not alter the relevant biological characteristics of cells or tissues." 21 C.F.R. 1271.3(f)(2).

i. "For purposes of determining whether a structural tissue product is minimally manipulated, a tissue characteristic is ‘original’ if it is present in the tissue of the donor. A tissue characteristic is ‘relevant’ if it could have meaningful bearing on how the tissue performs when utilized for reconstruction, repair, or replacement. A characteristic of structural tissue would be relevant when it could potentially increase or decrease the utility of the original tissue for reconstruction, repair or replacement."

Office of Combination Products and Center for Biologics Evaluation and Research, Guidance for Industry and FDA Staff: Minimal Manipulation of Structural Tissue Jurisdictional Update (2006).

2. If processing has altered an original, relevant characteristic of a structural tissue (the so called "kick-up factors"), it will be considered to have been more than minimally manipulated. In this case, the structural tissue will be regulated as a drug, device and/or biological product and will be subject to the pre-market approval process.

Stem cells that have been created from bone marrow are already being tested in controversial human clinical trials. The FDA has categorized these stem cells as investigational new drugs (INDs) by applying the above kick-up factors. Designation as a new investigational drug means that scientists must file an IND application and obtain the FDA’s approval prior to starting human clinical trials.

Will the method that is used to generate the stem cell technology make a difference in whether the FDA approves the IND application? In light of current questions regarding the role of politics in FDA decision-making, some may wonder.

The FDA’s current position is that it will apply the same procedures that it has long followed for the clinical testing of new drugs. This reliance on pre-existing law, rather than proposing a new regulatory strategy specifically tailored to this new technology based on therapeutic cloning, appears to bar the FDA from playing any role in the broader ethical and moral debate. As such, regardless of whether the stem cells were generated through reprogramming of human skin cells or from cloning a human embryo, the role of the FDA in approving clinical trials is statutorily limited to performing a risk analysis focusing solely on the issue of safety. Moral and ethical issues should be irrelevant to this calculus.

But what if the FDA approves clinical trials of stem cells from reprogrammed skin cells, but not those derived from therapeutic cloning that results in the destruction of human embryos? Would this denial be ‘end game’ for these scientists?

According to an article written by Richard A. Merrill and Bryan J. Rose, entitled FDA Regulation of Human Cloning: Usurptation or Statesmanship, 15 Harv. J.L.Tech. 85 (2001), maybe not. Professor Merrill suggests that the FDA strategy for the regulation of therapeutic cloning technologies may be suspect. Merrill posits that the FDA’s failure to provide notice and comment on its claimed authority to regulate this new technology may place this issue squarely into the realm of cases like Syncor International Corp. v. Shalala, 127 F. 3d 90 (D.C. Cir. 1997) and Northwest Tissue Center v. Shalala, 1 F. 3d 522 (7th Cir. 1993) which confront rule making’s substantive-interpretive distinction. The FDA’s strategy also suffers from vagueness problems with its ‘minimally manipulated’ dichotomy.

Adding to Merrill’s critique, any decision based on the method of production rather than the end product itself would run counter to the general theme of bioequivalency that pervades the FDA’s regulation of all of the products under its aegis.

All this leaves one to wonder whether, in the race to mimic human embryonic stem cells, will crossing the finish line mean a showdown with the FDA over therapeutic cloning? If so, will who wins the race determine whether people with life threatening diseases also become winners?

Brain Waves Reveal Intensity of Pain: Neural Signal Offers Objective Measure of Subjective Experience.

On the Neuroethics & Law Blog several months ago, Adam Kolber posted the following:

A couple of days ago, the NYT ran an article on the use of real-time functional magnetic resonance imaging (fMRI) to treat pain and perhaps a host of other symptoms like addiction and depression. The technology works like a kind of high-tech biofeedback:

"Here’s how Omneuron uses fMRI to treat chronic pain: A patient slides into the coffin-like scanner and watches a computer-generated flame projected on the screen of virtual-reality goggles; the flame’s intensity reflects the neural activity of regions of the brain involved in the perception of pain. Using a variety of mental techniques - for instance, imagining that a painful area is being flooded with soothing chemicals - most people can, with a little concentration, make the flame wax or wane. As the flame wanes, the patient feels better. Superficially similar to an older technology, electroencephalogram biofeedback, which measures electrical feedback across multiple areas of the brain, fMRI feedback measures the blood flow in precise areas of the brain."

By giving users feedback about their pain, the technique attempts to create a visual representation of an individual's pain. That's pretty impressive! But imagine if we could make interpersonal judgments of pain. That could really change the way we identify malingerers and the way we calculate damages in court. As I've noted, I think that new neurotechnologies may someday move us in that direction.

In the article that Professor Kolber is referring to, he addresses a future which could bring neuroimaging into the court room as objective evidence of the degree of pain that an individual is suffering:

Pain is a fundamentally subjective experience. We have uniquely direct access to our own pain but can only make rough inferences about the pain of others. Nevertheless, such inferences are made all the time by doctors, insurers, judges, juries, and administrative agencies. Advances in brain imaging may someday improve our pain assessments by bolstering the claims of those genuinely experiencing pain while impugning the claims of those who are faking or exaggerating symptoms. These possibilities raise concerns about the privacy of our pain. I suggest that while the use of neuroimaging to detect pain implicates significant privacy concerns, our interests in keeping pain private are likely to be weaker than our interests in keeping private certain other subjective experiences that permit more intrusive inferences about our thoughts and character.

Kolber, Adam J., "Pain Detection and the Privacy of Subjective Experience" American Journal of Law & Medicine (Brain Imaging & The Law Symposium), Vol. 33, p. 433, 2007. Available at SSRN: http://ssrn.com/abstract=976831

The future that Professor Kolber described may have come one step closer as the result of a study that was published this week in Nature:

Brain Waves Reveal Intensity of Pain: Neural Signal Offers Objective Measure of Subjective Experience.

Recordings from electrodes in the human brain may offer the first objective way to measure the intensity of pain. Researchers say that they have found a neural signal that correlates with the amount of pain that an individual feels. The signal could be used to refine pain-relief techniques that involve stimulating the brain with electricity, they say.
Single cells have previously been identified in the human brain that are active in pain, but their response is binary, signaling either pain or no pain. Now, Morten Kringelbach of the psychiatry department at the University of Oxford, UK, and his colleagues have identified low-frequency brain waves that emanate from two regions buried deep within the brain when a patient is in pain. The more pain that is experienced, the longer the waves last.

"It is an objective measure that correlates with a subjective measure."

Published online 14 November 2007 Nature 450, 329 (2007) doi:10.1038/450329b

Certainly, this technology could be a blessing for the millions of us who suffer from chronic back pain. And it could remove the hurdle that claimants face who suffer debilitating injuries but have no objective measures to support their subjective claims of pain. In the dispute resolution context, Professor Kolber concludes that neuroimaging for pain detection should cause less concern over invasions of privacy than other, more invasive uses of this technology.

But place these new neurotechnologies into the context of programs such as the West Virginia Pilot Project and a different picture could emerge. In early 2007, the federal government approved the West Virginia Pilot Project which provides health care for low-income, medicaid beneficiaries. This program, and ones like it, is an attempt to respond to the ‘obesity crisis’ and the overall rise in health care costs.

The Pilot Project is described as an effort to encourage states to test approaches using more "personal responsibility" in Medicaid programs. West Virginia will ask Medicaid beneficiaries to sign a contract, under which they agree "to do my best to stay healthy" and attend "health improvement programs as directed," seek routine medical checkups and screenings, attend all scheduled physician appointments, and take medications as prescribed. Failure to meet these contractual obligations results in decreased health care benefits.

Will physician directed pain control, weight-loss or anti-smoking programs include undergoing procedures that involve invasions of ‘cognitive liberty’ in the name of public health? The fMRI technique described in the above New York Times article characterizes it as leading to "long-term changes in the brain." And procedures such as transcranial magnetic stimulation (described by Jeffrey Rosen in the New York Times article The Brain on the Stand) are being studied for use in turning off or inhibiting behavior, curing the "defective" brain.

Neuroimaging is already being developed for use in lie detection. As the regions of the brain are being scanned for pain management purposes or to alter eating or smoking behaviors, will information be gathered on lack of compliance with physician and program directives? Will the physician be turned into an agent of the state; a policeman reporting on program violations that will negatively impact a patient’s access to health care?

As Professor Kolber points out, case law is merely suggestive of a right to "thought privacy" and how the courts will deal with this issue is unclear.