HealthLawProf Blog

Drug Label, Maimed Patient and Crucial Test for Justices

The New York Times reports that the Supreme Court will hear arguments about whether plaintiffs have the right to sue when the products that hurt them had met federal standards.  Adam Liptak writes,

When Diana Levine starts talking about her rock ’n’ roll days, she plays a little air guitar, mimicking the way she used to handle her electric bass in bands like the Re-Bops and Duke and the Detours. But Ms. Levine is missing much of her right arm, which was amputated below the elbow after a medical disaster.

She sits at her kitchen table, strumming an imaginary guitar with a phantom hand.

In November, the Supreme Court will hear arguments about whether Ms. Levine may keep more than $6 million that a Vermont jury ordered Wyeth, a pharmaceutical company, to pay her for failing to warn her adequately about the risks of one of its drugs. The case, the latest in a brisk parade of similar ones, will help define the contours of a signature project of the Roberts court.

In legal jargon, the cases concern “pre-emption,” a doctrine that can bar injured consumers like Ms. Levine from suing in state court when the products that hurt them had met federal standards. The issue is less boring and more consequential than it sounds, and Ms. Levine’s case is shaping up to be the most important business case of the term.

“Federal pre-emption is the fiercest battle in products liability law today,” said Catherine M. Sharkey, a law professor at New York University. “The court clearly recognizes this, as it has agreed to hear so many cases and seems eager to give clarity to what has been, to date, an undisputably muddled area of law.”

A second pre-emption case, this one concerning cigarette labels, is scheduled for the first argument of the new term, on Oct. 6.

Business groups, often supported by the Bush administration, have vigorously pursued pre-emption arguments, hoping to build a barrier against many kinds of injury suits. Plaintiffs’ lawyers oppose broad pre-emption doctrines, saying they short-circuit valid claims arising from terrible injuries.

Ms. Levine is a trim, elegant 62-year-old who now favors three-quarter length sleeves, just long enough to cover what remains of her right arm. But she gestures enthusiastically with both arms, and she retains a playful side.

Her house is jammed with whimsical toys — a papier-mâché giraffe, an enormous telephone receiver. In the control room of her recording studio, there is a copy of “Hand, Hand, Fingers, Thumb,” a children’s book. “It’s just sarcasm,” she explained.

In the spring of 2000, suffering from a migraine, Ms. Levine visited a clinic near here for a treatment she had received many times: Demerol for the pain and Wyeth’s drug Phenergan for nausea.

“Nothing wrong with either drug,” Ms. Levine said. “They’re both safe when given the right way.”

But if Phenergan is exposed to arterial blood, it causes swift and irreversible gangrene. For that reason, it is typically administered by intramuscular injection. According to Ms. Levine’s lawyers, using an intravenous drip is almost entirely safe as well.

This time, though, a physician’s assistant used a third method. She injected the drug into what she thought was a vein, a method known as “IV push.” But the assistant apparently missed.

In the following weeks, Ms. Levine’s hand and forearm turned purple and then black, and they were amputated in two stages.

The drug’s label, approved by the Food and Drug Administration, had warned that “inadvertent intra-arterial injection” can result in “gangrene requiring amputation.” But it did not rule out administration of the drug by IV push.

Ms. Levine said no one had discussed the risks of IV push with her, or the only benefit generally associated with intravenous administration — “more potent and expeditious antinausea relief,” in the words of Wyeth’s brief.

“The benefit-risk is just outrageously ridiculous,” Ms. Levine said. “Any child could figure this out.”

Faster nausea relief, she said, is not worth the risk of losing an arm.

Ms. Levine settled a lawsuit against the clinic, and she went to trial in Montpelier, not far from here, against Wyeth. She said Wyeth should have added a stronger warning to the label that the F.D.A. had approved.

“All they had to do,” Ms. Levine said, “was change the label and say, ‘Don’t give it this way.’ ”

Lawyers for Wyeth said that was not an option, at least in the absence of new information. “Wyeth could not change Phenergan’s labeling to comply with Vermont law without violating federal law,” they wrote in a brief. Ms. Levine’s lawyers disagreed, saying that tougher warnings were always permissible.

Continue reading "Drug Label, Maimed Patient and Crucial Test for Justices"

Public Needs to Know Vaccines Are Safe, Docs Say

The Washingtong Post reports that a new coalition of 22 major medical groups says public confidence in vaccine safety needs to be restored to avoid risks for deadly disease outbreaks. The Washington Post writes,

Thursday's message comes from the Chicago-based American Medical Association, the American Academy of Pediatrics and 20 more of the nation's most influential health-related groups.

Their concern stems from recent measles outbreaks in several U.S. cities. Last month, health officials said 131 children had gotten the measles so far this year _ the highest number in more than a decade. Nearly half of the cases involved children whose parents rejected vaccination and many of the cases were traced to outbreaks overseas.

"The ongoing measles outbreaks in several states are testimony that those who forgo vaccinations are vulnerable to infection from imported disease, and can pose a significant health risk for their communities," said AMA board member Dr. Ardis Hoven, an infectious disease specialist.

Recent government data show that more than 77 percent of U.S. toddlers have gotten all their recommended shots. The doctor groups said that means about one-fourth of toddlers aren't getting the shots they need.

The alliance said public health officials need to counteract campaigns by advocacy groups who believe vaccines can cause autism, despite scientific evidence to the contrary.

"We do not want to become a nation of people who are vulnerable to diseases that are deadly or that can have serious complications, especially if those diseases can be prevented," Dr. Renee Jenkins, the American Academy of Pediatrics' president, said in a statement.

The alliance suggests several ways to boost confidence in vaccines, including urging the government to create a public information campaign, and calling for more vaccine research.

FTC Warns Consumers About Bogus Cancer Cures

The Washington Post reports that the FDA along with Canadian authorities are launching a consumer education campaign warning about bogus claims for cures after the FTC charged five companies with making false and misleading claims.  Randolph E. Schmid writes,

The Federal Trade Commission charged five companies with making false and misleading claims for cancer cures and said Thursday that it has reached settlements with six others. "As long as products have been sold there has been somebody out there selling snake oil to consumers," said Lydia Parnes, director of the FTC's bureau of consumer protection.

She said the agency, along with the Food and Drug Administration and Canadian authorities, is launching a consumer education campaign warning about bogus claims for cures.

"There is no credible scientific evidence that any of the products marketed by these companies can prevent, cure, or treat cancer of any kind," said Parnes.

The products the companies marketed include essiac teas and other herbal mixtures, laetrile, black salve, a corrosive ointment, and mushroom extracts.

Richard Jaffe, a Houston attorney who represents Native Essence Herb Company, one of those named by the FTC, argues that the government is trying to censor his client.

The company sells herbs over the internet and advises people that some herbs have a historical use for treatment of cancer and other medical conditions, he said. That is a truthful claim, he said, adding that because an herb was used by ancient Chinese or native Americans doesn't mean it works, "which most people understand."

In addition the agency wants to block reports on trials in other parts of the world, he said, because they might imply a claim.

"In our view it's a battle between the right to speak and the government's censorship," Jaffe said.

Douglas Stearn of the FDA said his agency is concerned that people may forgo effective cancer treatments when choosing these products. In addition, he said, some of these unproven products may have dangerous interactions with other drugs.

"We would urge folks to talk to their doctors," said Stearn.

Parnes said more than 100 warning letters were sent out and many advertisers dropped or changed their claims.

Of the complaints resolved by settlements, she said companies paid restitution ranging from $9,000 to $250,000.

The remaining five complaints of false and deceptive advertising will go before administrative law judges, she said.

Those cases are Omega Supply, San Diego, Calif.; Native Essence Herb Company, El Prado, N.M.; Daniel Chapter One, Portsmouth, R.I.; Gemtronics, Inc., Franklin, N.C., and Herbs for Cancer, Surprise, Ariz.

Action Is Sought to Ensure Timely Financing for V.A.

The New York Times reports that a new effort to approve money for veterans' medical care one year in advance is being spearheaded by the chairmen of the Veterans' Affairs Committees in the House and Senate.  Lizette Alvarez writes,

As the veterans’ health system strains to handle a growing caseload, a move is under way in Congress to avoid yearly delays in financing that can hamper the medical care of the nation’s veterans.

The legislation would allow Congress to approve the money for veterans’ medical care one year in advance. In so doing, it would separate veterans’ health care financing from the crush of appropriations and political horse-trading that take place at year’s end.

The so-called advanced appropriation is already used to ensure the timely delivery of money to other programs, including the Low Income Home Energy Assistance Program and Housing and Urban Development vouchers for low-income renters.

The effort is being spearheaded by the chairmen of the Veterans’ Affairs Committees in the House and Senate. They say the long delays in getting the money for health care to the Department of Veterans Affairs is untenable in a time of war.

“The Department of Veterans Affairs operates the largest health care system in the nation, but its funding is untimely and unpredictable,” said Senator Daniel K. Akaka, the Hawaii Democrat who is chairman of the Senate veterans committee.

“Unlike Medicare and Medicaid,” Mr. Akaka said, “V.A. never knows what its level of funding will be for the next year. V.A. health care providers are tied down by uncertainty. This situation is bad for taxpayers, bad for V.A. and bad for veterans.”

Representative Bob Filner, the California Democrat who heads the veterans committee in the House, said the measure was a compromise that did not call for mandatory financing for veterans’ programs.

Explaining that Congress has been routinely late in passing the spending bill, Mr. Filner said, “You can’t run an agency if you can’t get timely funding.”

The last time Congress approved Department of Veterans Affairs money by Oct. 1, the start of the fiscal year, was in 1997. Congress failed to pass this year’s spending bill for the agency until February.

Waiting for Congress to pass spending legislation is a parlor game in Washington and few agencies ever get their money on time.

But Mr. Akaka and an umbrella group of major veterans organizations say the delays pose a critical problem when it comes to providing medical care for veterans, especially at a time of exploding growth.

The delays, they say, affect service to veterans, including waits for appointments; hamper the hiring of personnel; and hinder equipment purchases.

At the same time, the department has been under intense pressure to serve veterans better.

“It has a real impact on services,” said Joseph A. Violante, the legislative director for Disabled American Veterans, part of the umbrella group Partnership for Veterans Health Care Budget Reform.

FDA Proposes Approval Process for Genetically Engineered Animals

The Washington Post reports that the FDA will release today long-awaited regulatory guidelines governing genetic engineering of animals for food, drugs or medical devices.   David Brown writes,

Although none of the provisions is likely to surprise the biotech industry, their formal appearance after years of discussion is expected to energize a field whose commercial potential is huge but so far unrealized.

The agency's regulatory control of animals will be considerably stronger than its oversight of genetically engineered plants and microorganisms. The latter -- or substances derived from them -- are on the market and, in some cases, have proved controversial.

The guidelines tell companies what the FDA wants to know about their work at virtually every stage of creating an engineered animal.

For example, biotech firms will be asked to provide the molecular identity of snippets of DNA inserted in an animal's genome, as well as where the genetic message lands and whether it descends unaltered through subsequent generations. The FDA also wants to be told how the genetic alterations might change an animal's health, behavior and nutritional value.

The companies also should inform the agency how they will keep track of animals, prevent them from mingling with their non-engineered cousins and dispose of them when they die.

Genetically engineered animals -- salmon, pigs, cows and goats are in development -- are expected to have two main uses. Some will be food animals whose new genetic endowment makes them disease-resistant, faster-growing or more nutritious. Others will be genetically engineered to produce medically useful substances, such as hormones or antibodies, in their organs or body fluids.

Pigs that are able to more easily absorb phosphorus, and therefore need less feed supplementation, are being developed in Ontario. Goats that produce spider silk in their milk are being made in Wyoming.

Food that is produced from genetically engineered animals will not have to be labeled as such. However, if the genetic manipulation changes the nutritional content -- for example, by increasing a beneficial form of fat -- that must be declared on the label.

The specific requests in the guidelines are not mandatory. However, biotech companies seeking FDA approval to commercialize genetically engineered animals must follow federal drug laws. The guidelines are meant to show how they can do that.

The FDA has been providing the advice on an informal basis for about 10 years, said Eric Flamm, a policy adviser at the agency. The guidelines will be open for public comment for 60 days.

"We are simply clarifying what we've always done, and will continue to do," he said.

There was general agreement that something in writing on the subject has been needed for a while.

"It is past due for the federal government to finally recognize that genetically engineered animals are on the horizon and need regulation and oversight," said Gregory Jaffe of the Center for Science in the Public Interest, a lobbying organization in Washington.

The action "will drive investor confidence," said Barbara Glenn of the Biotechnology Industry Organization. "They know that we will reach commercialization of a product." At the moment, about a dozen of the organization's 1,200 member companies are developing genetically engineered animals, she said.

But the new guidelines drew criticism from groups worried about possible environmental, ecological and physiological hazards of bioengineered animals. The experience of genetically modified plants is rife with examples of unintentional dissemination of the organisms, and their interbreeding with unmodified members of their species.

"The first time that the public will learn about a genetically engineered animal will be the day it is approved," said Margaret Mellon of the Union of Concerned Scientists. "This requires that you completely trust the FDA to do this right, and I don't think folks trust FDA that much."

Michael Hansen, a scientist with Consumers Union, publisher of Consumer Reports magazine, said that "there is very little transparency without [the FDA] laying out all the data" for the public to see. He does not think that transparency is assured.

The FDA is laying claim to regulatory authority over what it calls "GE animals" through an unusual legal argument.

The Food, Drug and Cosmetic Act defines a drug as anything that alters the "structure or function" of a person or animal. Adding a gene to an animal through recombinant technology changes at least the animal's structure and probably its function, as well.

In the new guidelines, the FDA argues that "recombinant DNA constructs" inserted into animals are by definition drugs. However, because the DNA constructs are physically inseparable from the whole animals, the latter also fall under the agency's regulatory control.

"You can't regulate the drug without regulating the animal," said Flamm, the FDA policy adviser. "So, effectively, we are putting controls on the animal rather than on the little piece of DNA."

With this strategy, virtually no genetically engineered animal will escape FDA scrutiny during its development and testing. This is not true with plants.

The FDA regulates genetically modified plants whose nutritional content is altered, in which case they become "food additives." The Environmental Protection Agency regulates them when the new genetic endowments provide pesticide-like actions.

Although the animal-is-drug strategy will allow the FDA to regulate genetically engineered animals without getting further authority from Congress, the unintended effects of that strategy worry some consumer groups.

Although companies will have to provide detailed information about their work starting from the earliest stage, the FDA is prohibited by law from revealing that information to the media or the public. That is because much of the information is proprietary, competitive and extremely valuable. The agency cannot even acknowledge that a company has a "new drug application" on file.

Consequently, discussions that occur during the development of a genetically engineered animal about its safety and effectiveness will not include consumer or watchdog groups.

Although the guidelines say that the FDA may ask a company to submit an environmental impact statement with its application for approval of a genetically engineered animal, the agency cannot reject a drug strictly on environmental grounds.

Some groups are worried about the effects of unanticipated mixing of genetically engineered animals with others -- for example, the escape of fast-growing salmon into the open ocean, where they could breed with wild species.

"I don't think what's being announced will protect humans and the environment from all the potential risks that a genetically engineered animal may pose," said Jaffe of the Center for Science in the Public Interest.

HIV Epidemic in U.S. A Crisis, Health Officials Say

The Los Angeles Times reports that federal health officials are urging additional programs to protect African Americans, Latinos, and gay and bisexual men about the increased risks and prevention of HIV infections.  Cynthia Dizikes writes,

The HIV epidemic in the United States is a crisis, federal health officials told a House panel Tuesday, urging additional programs to specifically protect and educate African Americans, Latinos and gay and bisexual men -- the groups hardest hit by the virus that causes AIDS.

Their testimony before the House Committee on Oversight and Government Reform came a little more than a month after the Centers for Disease Control and Prevention released a study indicating that new HIV infections in the United States had been underestimated by 40% every year for more than a decade. The study concluded that there are about 56,300 new infections each year, not the 40,000 usually cited.

"We need to do so much more than we're doing right now," said Dr. Julie Gerberding, director of the CDC. "And we need to get AIDS back on the radar screen. . . . This is something that is still posing a threat to college students and to young men and women across our nation's fabric."

The new numbers, published last month in the Journal of the American Medical Assn., were found through improved testing and were not an increase in new infections, which have remained relatively constant since the late 1990s.

The higher estimates, however, served as a reminder that preventing transmission of the human immunodeficiency virus is still an issue in the United States, where the prevalence of HIV is greater than in Canada, Australia, Japan or any Western European country except Switzerland.

More than 1 million Americans are HIV-positive, according to the CDC, and more than 15,000 Americans die of acquired immune deficiency syndrome each year.

"The message these new findings sends is clear: We're not doing enough to limit the spread of this deadly disease," said Rep. Henry A. Waxman (D-Beverly Hills), the committee chairman.

Perhaps even more disturbing than the overall hike in HIV cases were the disparities the new numbers laid bare.

Gay and bisexual men accounted for 53% of the new infections in 2006, the most recent year for which data are available. Blacks, who make up about 12% of the total population, accounted for 45% of the new HIV infections. The infection rate among blacks was a staggering seven times higher than among whites, and the rate among Latinos was nearly three times higher.

"Serious HIV-related health disparities, often fueled by stigma and discrimination, continue to undermine HIV prevention efforts in communities of color," Dr. George Ayala of AIDS Project Los Angeles told the panel.

Young black gay men have been especially hard hit, representing 48% of new infections among gay and bisexual males ages 13 to 29. Yet only four of the CDC's 49 recommended intervention programs specifically target gay men, and only one of them is designed to address gay men of color, according to Ayala.

The 2009 budget request for domestic HIV prevention efforts is $892 million, a slight decrease from last year. That figure includes $752.6 million requested by the CDC. On Tuesday, Gerberding told the committee that based on the new data, the CDC would need an additional $877 million in 2009 and an additional $4.8 billion over the next five years.

In July, President Bush signed legislation reauthorizing U.S. participation in a global program against HIV/AIDS.

Waxman said he would try to work with the Appropriations Committee to increase funding for domestic HIV prevention programs this year, but he was "not very optimistic" it would result in an allocation change under the current administration.

"I think the purpose of this hearing has been to sound an alarm," Waxman said.

Exposure to Chemical in Plastics Poses Risks

The Los Angeles Times reports that in the first large-scale human study of the chemical, some found with bisphenol A in their urine had more than double the normal risk of heart disease and diabetes.  Thomas H. Maugh II writes,

The first large-scale human study of a chemical used to make plastic baby bottles, aluminum can linings and myriad other common products found double the risk of cardiovascular disease, diabetes and liver problems in people with the highest concentrations in their urine, British researchers reported Tuesday.

The findings confirm earlier results obtained in animals, increasing pressure on the U.S. Food and Drug Administration to limit use of the chemical bisphenol A, or BPA.

The compound is the primary ingredient of polycarbonate plastics, which are found in a wide variety of modern goods, including DVDs, reusable food storage containers, drinking bottles and eyeglass lenses.

There have been growing concerns about its safety as studies in rodents have linked it to diabetes, brain damage, developmental abnormalities, precancerous changes in the prostate and breast, and a variety of other health problems.

About 7 billion pounds of the chemical are produced worldwide each year, and studies by the federal Centers for Disease Control and Prevention have found that 93% of Americans have detectable levels in their urine.

The new findings were published in the Journal of the American Medical Assn., coinciding with an FDA hearing Tuesday in Washington on BPA.

"This is a human study that really calls into question FDA's assertion that BPA is safe," said Dr. Anila Jacob of the activist Environmental Working Group.

An FDA representative, however, defended the agency's actions at the hearing.

"A margin of safety exists that is adequate to protect consumers, including infants and children, at the current levels of exposure," said Laura Tarantino, a senior FDA scientist.

But many experts think the writing is on the wall for the chemical.

A draft report issued this year by the government's National Toxicology Program, which has no regulatory authority, concluded that there was "some concern" that the chemical posed a risk to fetuses, babies and children.

Health Canada, that country's national public health agency, also this year released a report calling BPA "a potentially harmful chemical" -- becoming the first regulatory body in the world to do so.

Baby bottle manufacturers are already looking for replacements for the chemical. And Wal-Mart Stores Inc. and Toys R Us Inc. have announced plans to shift away from products containing BPA.

BPA was first synthesized in 1891 and came into wide use in the 1940s and 1950s because of the durability and light weight of polycarbonates.

Some BPA remains intact in the plastic and leaches out over time, particularly when it comes in contact with hot liquids or acidic foods.

The chemical industry and the FDA have long relied on two large animal studies showing that high concentrations of the chemical fed to rodents produced no serious adverse effects.

There had been no previous large studies of the chemical in humans because researchers considered such testing inappropriate.

Dr. David Melzer of the Peninsula Medical School in Exeter, Britain, and his colleagues took advantage of results from the 2003-04 U.S. National Health and Nutrition Examination Survey, which for the first time measured concentrations of BPA in urine from a representative sample of 1,455 adults.

They found that the quarter of the group with the highest BPA levels -- levels still considered safe by the FDA -- were more than twice as likely to suffer from diabetes and cardiovascular disease as the quarter with the lowest levels.

The study, funded by the medical school, discovered no association with any other health effects.

But the findings were sufficiently troublesome that the FDA should take "aggressive action to limit human and environmental exposures," wrote biologists Frederick S. vom Saal of the University of Missouri and John Peterson Myers of Environmental Health Sciences in Charlottesville, Va., in an editorial accompanying the study.

Steven G. Hentges of the American Chemistry Council, whose members include polycarbonate makers, objected that the study's design, which measured BPA at only one point in time, "cannot support a conclusion that bisphenol A causes any disease."

The authors partially agreed, calling for follow-up studies to confirm their findings and prove whether the link is causal. But, Jacob noted, the similarities between the British results and those of animal studies suggest that it is.

The cause of the increased risk is unclear, but two studies this year offered some hints. Spanish researchers reported in April that in mice, BPA caused pancreatic cells to increase their production of insulin, leading to the well-known metabolic syndrome that is a precursor of diabetes and heart disease.

And an August study by endocrinologist Nira Ben-Jonathan of the University of Cincinnati showed that BPA, like estrogen, impaired the ability of human fat tissue to secrete adiponectin, which protects against heart attacks and diabetes.

Meanwhile, there are some steps consumers can take to avoid BPA. A Japanese study of college students suggested that the major dietary source of BPA was canned beverages. Glass and recyclable plastic soda and water bottles do not contain polycarbonates.

Glass baby bottles are safe, and at least one company makes plastic baby bottles containing no BPA.

Nonrecyclable plastic containers that are made with polycarbonates are marked with the number 7 on the bottom. BPA leaching can be reduced by not microwaving food in such containers.

FDA Bans Imports of 28 Indian-Made Drugs

The Washington Post reports that the FDA is halting importation of 28 drugs made by the giant Indian generic drug maker Ranbaxy Laboratories because of manufacturing deficiencies at two of the company's plants.  David Brown writes,

Douglas Throckmorton, a physician with the FDA's Center for Drug Evaluation and Research, said there was "no evidence of harm to consumers" from drugs made at the Dewas and Paonta Sahib plants, both in India. He called the import ban "a preventive action."

FDA officials said numerous tests of the drugs have found they are not contaminated, sub-potent or unsafe and urged patients taking the drugs not to stop.

The drugs on the list include numerous antibiotics and antivirals, as well as medicines for high cholesterol, diabetes, high blood pressure, seasonal allergies and acne.

FDA officials said the action is not expected to disrupt availability of the medicines to U.S. consumers. All but one -- oral capsules of the antiviral drug ganciclovir -- are made by other companies. Supplies of that medicine will be allowed in after batch-by-batch testing and assurances by the company on the manufacturing process.

Ranbaxy is India's biggest pharmaceutical company and one of the 10 biggest producers of generic drugs in the world.

FDA officials walked a delicate line yesterday, stressing the seriousness of the violations while offering assurances that the risk to the public is essentially zero.

"We believe this step is warranted because of the seriousness and the extent of the violations," said Deborah M. Autor, director of the office of compliance at the Center for Drug Evaluation and Research.

She added, however, that "all the products that we have tested met specifications" and that there is "no reason" to consider them hazardous.

"The nature of the violations really relates to the [manufacturing] process," Autor said. "We did not find any defects in the products themselves."

The FDA inspects the factories of foreign drug companies seeking to sell products in the United States. Because the plants are on foreign soil, the agency has no direct regulatory control over them. Its only leverage is to ban importation of the substances.

The FDA had sent two warning letters, the first in 2006, informing Ranbaxy management that inspectors had found numerous deviations from "current good manufacturing process" -- the long list of rules and standards for producing drugs.

"Since then, we've done a lot of work with the company to correct the deficiencies," Autor said. But many persisted, she said, so the agency took the next step.

Among the problems were "inadequate sterile processing operations"; failure to keep certain areas from being contaminated with compounds that can cause allergic reactions in some people; and inadequate record-keeping.

The company will not be able to export any of the 28 drugs to the United States until the deficiencies are fixed. In the interim, the FDA also will not consider any new drug applications for substances made at the two plants.

Meanwhile, the Justice Department is investigating allegations that Ranbaxy submitted fraudulent data to the FDA as part of its application for approval to sell certain AIDS drugs to organizations funded by the Bush administration's $15 billion President's Emergency Plan for AIDS Relief.

One of the drugs on yesterday's list is the antiretroviral AZT.

"We are currently working through the PEPFAR interagency process and with our technical teams to evaluate the impact of today's FDA announcement on PEPFAR drug procurement and programming," a program spokeswoman said yesterday.

FDA Defends Plastic Linked With Health Risks

The New York Times reports that although the FDA has defended their assessment that bisphenol A used in plastic baby bottles and water bottles is safe, studies are still being conducted that suggest adults exposed to higher amounts of bisphenol A are more likely to report having heart disease and diabetes.  The FDA concedes that further research is needed.  The New York Times writes,

Federal regulators on Tuesday defended their assessment that a chemical widely used in plastic baby bottles and in food packaging is safe, even as the first major study of health effects in people linked it with possible risks for heart disease and diabetes.

''A margin of safety exists that is adequate to protect consumers, including infants and children, at the current levels of exposure,'' Laura Tarantino, a senior Food and Drug Administration scientist, told an expert panel that has been asked for a second opinion on the agency's assessment of bisphenol A or BPA.

However, a study released Tuesday by the Journal of the American Medical Association suggested a new concern about BPA. Because of the possible public health implications, the results ''deserve scientific follow-up,'' the study authors said. Using a health survey of nearly 1,500 adults, they found that those exposed to higher amounts of BPA were more likely to report having heart disease and diabetes.

But the study is preliminary, far from proof that the chemical caused the health problems. Two Dartmouth College analysts of medical research said it raises questions but provides no answers about whether the ubiquitous chemical is harmful.

FDA officials said they are not dismissing such findings, and conceded that further research is needed. ''We recognize the need to resolve the concerning questions that have been raised,'' said Tarantino. But the FDA is arguing that the studies with rats and mice it relied on for its assessment are more thorough than some of the human research that has raised doubts.

The JAMA article was released to coincide with the FDA scientific advisers' hearing.

The FDA has the power to limit use of BPA in food containers and medical devices but last month released its internal report concluding that BPA exposure is not enough to warrant action.

Since then, another government agency released a separate report concluding that risks to people, in particular to infants and children, cannot be ruled out.

Past animal studies have suggested reproductive and hormone-related problems from BPA. The JAMA study is the largest to examine possible BPA effects in people and the first suggesting a direct link to heart disease, said scientists Frederick vom Saal and John Peterson Myers, both longtime critics of the chemical.

Still, they said more rigorous studies are needed to confirm the results.

Vom Saal is a biological sciences professor at University of Missouri who has served as an expert witness and consultant on BPA litigation. Myers is chief scientist at Environmental Health Sciences, a Charlottesville, Va., nonprofit group. They wrote an editorial accompanying the JAMA study.

BPA is used in hardened plastics in a wide range of consumer goods including food containers, eyeglass lenses and compact discs. Many scientists believe it can act like the hormone estrogen, and animal studies have linked it with breast, prostate and reproductive system problems and some cancers.

Researchers from Britain and the University of Iowa examined a U.S. government health survey of 1,455 American adults who gave urine samples in 2003-04 and reported whether they had any of several common diseases.

Participants were divided into four groups based on BPA urine amounts; more than 90 percent had detectable BPA in their urine.

A total of 79 had heart attacks, chest pain or other types of cardiovascular disease and 136 had diabetes. There were more than twice as many people with heart disease or diabetes in the highest BPA group than in the lowest BPA group. The study showed no connection between BPA and other ailments, including cancer.

No one in the study had BPA urine amounts showing higher than recommended exposure levels, said co-author Dr. David Melzer, a University of Exeter researcher.

Drs. Lisa Schwartz and Steven Woloshin of the Dartmouth Institute for Health Policy and Clinical Practice said the study presents no clear information about what might have caused participants' heart disease and diabetes.

''Measuring who has disease and high BPA levels at a single point in time cannot tell you which comes first,'' Schwartz said.

The study authors acknowledge that it's impossible to rule out that people who already have heart disease or diabetes are somehow more vulnerable to having BPA show up in their urine.

The American Chemistry Council, an industry trade group, said the study is flawed, has substantial limitations and proves nothing.

But Dr. Ana Soto of Tufts University said the study raises enough concerns to warrant government action to limit BPA exposure.

''We shouldn't wait until further studies are done in order to act in protecting humans,'' said Soto, who has called for more restrictions in the past.

An earlier lab experiment with human fat tissue found that BPA can interfere with a hormone involved in protecting against diabetes, heart disease and obesity. That study appeared online last month in Environmental Health Perspectives, a monthly journal published by the National Institutes of Health.

Government toxicology experts have also studied BPA and recently completed their own report based on earlier animal studies. They found no strong evidence of health hazards from BPA, but said there was ''some concern'' about possible effects on the brain in fetuses, infants and children.

Several states are considering restricting BPA use, some manufacturers have begun promoting BPA-free baby bottles, and some stores are phasing out baby products containing the chemical. The European Union has said that BPA-containing products are safe, but Canada's government has proposed banning the sale of baby bottles with BPA as a precaution.

China Makes Arrests Over Tainted Infant Formula

The Los Angeles Times reports that two brothers are held in Hebei province, home to Sanlu Group, which sold the contaminated milk powder.  Don Lee writes,

Chinese police Monday announced the first arrests in the spreading scandal over tainted milk powder as health officials reported that a second infant had died and 1,253 others had been sickened after ingesting the formula.

The arrest of two brothers in Hebei province, home of the state-owned Sanlu Group that sold the contaminated product, was among a flurry of actions announced by authorities in the wake of the latest food safety problem to hit China. Officials have seized or recalled more than 10,000 tons of Sanlu formula and have ordered a nationwide inspection of fresh milk and cattle feed.

The official New China News Agency, quoting a police spokesman in Hebei, said the brothers, surnamed Geng, had been running a private milk-collecting station since May 2004. The 48-year-old older brother had begun to put melamine into milk at the end of last year, and the younger brother sent the milk to Sanlu. The brothers were among 19 people detained.

Melamine, a chemical used in making plastics and fertilizers, has been used by Chinese businesses to artificially boost protein readings in animal feed and other food products. Pet foods containing melamine-laced ingredients traced to China sickened and killed thousands of dogs and cats in the U.S. last year.

Many infants who were fed Sanlu milk powder developed kidney stones. The two deaths were in Gansu province, a poor area in China's northwest. China's Health Ministry said at a news conference that as of Monday morning 53 babies were in critical condition and 340 others were hospitalized, according to the news agency.

Earlier Chinese media reports said that Sanlu, one of the nation's largest dairy companies, had been receiving complaints about its formula since March but had delayed reporting the problem to the government or issuing a public alert. Sanlu's vice president, Zhang Zhenling, read a letter of apology at a news briefing Monday in Shijiazhuang, capital of Hebei province. "We feel really sad about this," he was quoted as saying.

Sanlu is 43% owned by the New Zealand-based dairy giant Fonterra, which said it first learned of the problem Aug. 2. New Zealand Prime Minister Helen Clark said Monday that Fonterra tried unsuccessfully to get local Chinese authorities to order a full recall as soon as possible.

The delay in halting sales of the milk powder added to the anger and frustration of Chinese consumers, many of whom have come to mistrust food safety after a number of scandals. In 2004, baby formula missing key ingredients left at least 13 infants dead and hundreds ill from what local residents called "big head disease."

"It's cruel that they make money this way by endangering little babies," said Lin Jinyan, 23, who, with her 9-month-old son, was shopping at a supermarket in Shanghai. Clerks at the market said Sanlu baby formula had been removed from shelves over the weekend.

"I'm worried," Lin added. "We have no choice but to buy milk for babies."

Risks Found for Youths in New Antipsychotics

The New York Times reports on a new study that finds medicines most often prescribed for schizophrenia in youth are no more effective than older, cheaper drugs and are more likely to cause some harmful side effects.  Benedict Carey writes,

A new government study published Monday has found that the medicines most often prescribed for schizophrenia in children and adolescents are no more effective than older, less expensive drugs and are more likely to cause some harmful side effects. The standards for treating the disorder should be changed to include some older medications that have fallen out of use, the study’s authors said.

The results, being published online by The American Journal of Psychiatry, are likely to alter treatment for an estimated one million children and teenagers with schizophrenia and to intensify a broader controversy in child psychiatry over the newer medications, experts said.

Prescription rates for the newer drugs, called atypical antipsychotics, have increased more than fivefold for children over the past decades and a half, and doctors now use them to settle outbursts and aggression in children with a wide variety of diagnoses, despite serious side effects.

A consortium of state Medicaid directors is currently evaluating the use of these drugs in children on state Medicaid rolls, to ensure they are being prescribed properly.

The study compared two of the newer antipsychotics, Zyprexa from Eli Lilly and Risperdal from Janssen, with an older medication and found that all three relieved symptoms of schizophrenia, like auditory hallucinations, in many young patients. Yet half of the children in the study stopped taking their drug within two months, either because it had no effect or was causing serious side effects, like rapid weight gain. The children receiving Zyprexa gained so much weight that a government oversight panel monitoring safety ordered that they be taken off the drug.

The long-anticipated study, financed by the National Institute of Mental Health, is the most rigorous, head-to-head trial of the drugs in children and adolescents with this disorder. About three million Americans suffer from schizophrenia, and perhaps 40 percent first show symptoms in their teens or earlier.

“This is really a landmark study, because these newer drugs have been around for 12 years or so now, and there were fundamental questions for which we really didn’t have answers,” said Dr. Sanjiv Kumra, director of the division of child and adolescent psychiatry at the University of Minnesota, who was not involved in the study.

Dr. Kumra said the results revealed significant differences in the drugs’ side effects that should help doctors and patients choose among them.

“What this is saying is that all treatments work, at least for some people, and have serious risks for others,” he said. “It’s a trial-and-error process” to match people with the right medication.

Dr. Jon McClellan of the University of Washington, a co-author of the new study and of the current guidelines for treating childhood schizophrenia, said in a telephone interview that older schizophrenia drugs should now be considered as an alternative in some cases.

“Some of the children in this study gained 15 pounds or more in eight weeks,” Dr. McClellan said. “That’s as much as adults gain in a year on these medications. Children are especially susceptible to these side effects, and this has broad implications across the board, for the use of these agents to treat any disorder.”

Studies have found that more than 80 percent of prescriptions for atypical antipsychotics for children are to treat something other than schizophrenia, like autism-related aggression, bipolar disorder or attention-deficit problems. Some of these are approved uses; others are not.

The researchers, led by Dr. Linmarie Sikich of the University of North Carolina, recruited 119 young people, ages 8 to 19, who suffer from psychotic symptoms. The children received either Zyprexa, Risperdal or molindone, an older drug used to blunt psychosis. Neither the young patients nor the doctors treating them knew which drug was being taken, but the researchers told the youngsters and their parents that, if the medication was not working out, the family could switch to another one.

After eight weeks, 34 percent of the children taking Zyprexa, 46 percent of those on Risperdal, and 50 percent of those receiving molindone showed significant improvement.

But by that time so many of the patients had stopped taking the drug they were on that it was not clear that those differences were significant. Many had gained a lot of weight: an average of about nine pounds for those in the Risperdal group, and 13 pounds in the Zyprexa group.

Both groups also showed changes in cholesterol and insulin levels that are risk factors for diabetes. Those taking molindone gained less than a pound, on average, and had little metabolic changes.

“I thought the extra weight was putting a lot of pressure on me,” said Brandon Constantineau, 18, a study participant in Wilmington, N.C., who gained 35 pounds while taking Risperdal for several months. “Kids at school were making fun of me, all that. I knew I had to get rid of it. I exercised a lot, but it didn’t happen until I changed drugs.”

Mr. Constantineau said he was now doing well on a medication not offered in the study.

Dr. Sikich, the study’s lead researcher, said, “One implication of this study is that the guidelines for treating schizophrenia need to be revised, so that some of the milder, traditional or older medications are considered first-line treatments in some cases.” She added: “The other significant thing is that none of these medications were as well tolerated as we had hoped. We really need to find better alternatives.”

Spokesmen for Eli Lilly and Janssen said that their drugs were not approved to treat schizophrenia in children and that, given the limited number of options for such patients, there was a need for new therapies.

Jamaison Schuler, a spokesman for Eli Lilly, pointed out that the new study, at eight weeks in length, had not lasted long enough to pick up the most worrisome side effect associated with the older drugs: Parkinson’s-like movement problems, which are often irreversible. Patients in the study taking molindone also took another drug to reduce this risk.

Beginning in the early 1990s, psychiatrists turned to the newer drugs in large part to spare their patients those problems. Several large studies since then have shown that that shift — while perhaps sparing some patients movement problems — has had a cost.

A landmark comparison of older and newer drug in adults with schizophrenia, published in 2005, had findings similar to the new report. Most patients in the earlier study stopped taking the drug they were put on, and some of the medications were associated with rapid weight gain and other problems.

“I think the reason the use of these newer drugs has gone up so fast is that there was this widespread assumption that they were safer and more effective than what we had before,” Dr. McClellan said. “Well, we’re seeing now that that’s not the whole story.”

Ruling Inspires New Hope For Transgender People

The Washington Post reports that with the decision by Maryland's highest court last week to block a referendum petition, Montgomery County's law banning discrimination against transgender people takes effect immediately. The measure, passed by the County Council last year, prohibits discrimination in housing, employment and public accommodations.  Ann E. Marimow writes,

To Allyson Robinson, it means accompanying her young children to public restrooms in Montgomery County without worrying that someone will call the police.

For Colleen Fay, it brings the hope that the next time she applies for a driver's license she won't be badgered about her previous life as a man.

And for Chloe Schwenke, it means other people like her will be able to enjoy the job security she has found in her international development work in the District.

With the decision by Maryland's highest court last week to block a referendum petition, Montgomery County's law banning discrimination against transgender people takes effect immediately.

The measure, passed by the County Council last year, prohibits discrimination in housing, employment and public accommodations. It was to take effect in February but was put on hold when some religious and conservative groups launched a petition drive.

The court's ruling was an important political and symbolic victory for gay and transgender rights advocates. Council member Duchy Trachtenberg (D-At Large), the bill's main sponsor, and Equality Maryland, the group that led the legal challenge, hosted a celebration Friday night at Jackie's Restaurant in Silver Spring.

But in interviews after the court's decision, transgender people throughout the Washington region said Montgomery's new law would be most meaningful in making the mundane details of day-to-day life a little bit easier. And they hope that it spurs action in neighboring jurisdictions.

"So I can walk into the office, wear a skirt and not be quite so afraid," said Fay, a transgender woman who lives in Prince George's County. "The little tiny things in life that most of the rest of humanity take for granted, we look at and say, 'That could be a hurdle as tall as the Empire State Building.' "

Opponents of the law, including some parents and religious groups, gathered more than 25,000 signatures to put the measure to a vote. They worried that the law was written so broadly that it could allow a cross-dressing man, for instance, to gain access to locker rooms at health clubs. They also unsuccessfully tried to add exceptions to the law for hiring by religious institutions and schools. To opponents, the court's decision disenfranchised the thousands of people who signed petitions.

But for transgender women such as Robinson, the County Council's passage of the law was a key reason she chose to live in Montgomery when she moved to the area this year from Texas to take a job at the Human Rights Campaign, a gay and transgender civil rights organization.

Before settling on a townhouse in Gaithersburg, Robinson and her family sought to rent an apartment. She worried, unnecessarily as it turned out, that the landlord would want to pull out of the lease upon meeting her. Until the law took effect this week, Robinson said, the landlord could have rejected her application because she is a transgender person.

In the past, Robinson has also worried about taking her four young children to public restrooms at restaurants, because she fears that someone will identify her as a transgender woman and call security.

Continue reading "Ruling Inspires New Hope For Transgender People"

Legal Fight Over Drug Liability Law

The Los Angeles Times reports that a Supreme Court ruling may reinterpret a statute that now allows consumers to sue drug makers over serious side effects.  Jill U. Adams writes,

Prescription drugs sometimes cause serious side effects. A ruling by the U.S. Supreme Court expected this fall could radically alter consumers' ability to seek recourse from drug makers should they suffer harm. The case, called Wyeth vs. Levine, may lead to a new interpretation of federal law, which would shield pharmaceutical companies from the most common kind of lawsuit.

If you experience a serious reaction that you suspect may be linked to a medication you took, what can you do now, and how would a ruling in favor of the drug companies change that? We asked some consumer healthcare advocates.

The first hurdle is to determine whether the drug is very likely to be the cause. You should talk to your doctor about what's happening to you, and maybe stop taking the drug after consulting with him or her.

If the drug seems to be to blame, you can report it to the Food and Drug Administration on its MedWatch website ( www.fda.gov/med watch). The FDA encourages you to seek your doctor's help in filling out the form, but it's not required.

These actions will not be affected by the Supreme Court ruling, but your ability to seek damages will be.

Now, if a medication has caused you severe or irreparable harm, you can consult with a lawyer and consider suing those who gave you the drug (the healthcare provider that prescribed or administered it) or those who made the drug (usually a pharmaceutical company).

The case before the Supreme Court is based on an argument that is used in the vast majority of lawsuits involving prescription drugs: that the drug company failed to adequately warn about a known risk of its product.

All drugs approved by the FDA are extensively labeled with information on dosing and administration, side effects, precautions and warnings. That label, in addition to the medication itself, must be reviewed and approved by the FDA.

If the ruling this fall is made for the defendant -- the pharmaceutical company Wyeth -- it would tilt the playing field largely in favor of the pharmaceutical industry, by stating that such claims against drugs are preempted because experts at the FDA sanctioned the product and its label for safety. Because federal law supersedes state law, the ruling would affect lawsuits filed in all 50 states.

Consumer advocates say this tilt would be unfair, because consumers should have a remedy against a drug company that sold them a defective drug or didn't fully disclose its side effects. "This is as sweeping a legal decision as the Supreme Court has ever made for prescription drug users," says Jamie Court, president of Consumer Watchdog, a consumer rights organization based in Santa Monica. "This preemption is exactly what the drug companies have sought for the last 20 years from Congress."

Congressional leaders are already drafting legislation that would restore liability if the Supreme Court rules for Wyeth, Court says.

Wyeth's position is that the adequacy of warnings on its FDA-approved drug label is an issue for experts at the FDA to decide, not juries.

Two types of cases

Currently, two main arguments are used by plaintiffs in pharmaceutical product liability cases: "failure to warn," meaning that the drug company failed to adequately warn consumers about possible side effects of the drug, and "design defect," that the drug is defective.

Failure to warn typically involves labeling issues, as in the case currently before the Supreme Court. The Wyeth drug Phenergan, used to relieve nausea, was labeled with a warning about risks if the drug were injected in a certain way -- and that risk became reality for plaintiff Diana Levine when she lost an arm to gangrene. Levine's argument is that the risk was high enough and serious enough that the label should have told users not to inject the drug that way.

No patient should be subject to such a serious risk, even if its likelihood is rare, for a condition that, although uncomfortable and distressing, is so nonthreatening to life and physical health, says Brian Wolfman, director of litigation at Public Citizen, a consumer advocacy group in Washington, D.C., and legal team member for Levine.

"The risks and benefits are out of whack," he says. On the one hand, "the patient was sick to her stomach." But on the other, "it's a serious, serious risk -- you lose your arm."

The "design defect" argument refers to adverse effects of a drug that were unknown at the time of a drug's approval and labeling. Rare reactions, the type that might affect 1 in 10,000 or 1 in a million, can become apparent only after a drug that was clinically tested in thousands of patients gets prescribed to millions of patients.

Most likely, advocates say, only one of these two arguments would be affected if Wyeth wins the Supreme Court ruling. An individual could still file a suit against the drug's maker for defects in manufacturing or design. But it couldn't do so for "failure to warn."

That is a serious change for the consumer, Wolfman says, because design-flaw arguments make up a tiny proportion of the drug-liability cases. "The principal claim in virtually all drug product liability cases is failure to warn about hazards," he says.

Because plaintiffs' lawyers foot the bills on product-liability cases -- working for a slice of the award -- they take cases they think they can win.

"If you take the most likely cause of action away, the calculations for the plaintiff's lawyer become much more dire," says Gary Marchant, professor of emerging technologies, law and ethics at Arizona State University. "It will change the dynamics of which cases are brought. Only the much stronger, the real sure-win kind of cases will be brought. The iffy ones will become financially unviable."

Personal-injury lawyers hope the ruling goes toward the plaintiff. "Pharmaceutical drugs right now are probably the hottest area of liability," Marchant says. The pharmaceutical industry and the Bush administration believe the excess of product liability cases must be reined in, Wolfman says.

Doctors side with Levine. In July, the New England Journal of Medicine published an editorial saying that by effectively taking away the right to sue, a Supreme Court decision favoring Wyeth would reduce the safety of drugs.

"It would be a sea change," Wolfman says. "It would be a ruling in the industry's favor that would result in massive change."

Controlled Drugs Dumped Uncontrolled Into Water

The Washington Post reports that because of strict rules meant to keep controlled pharmaceuticals out of the wrong hands, it is nearly impossible to handle controlled drugs safely as waste and often end up being thrown down sinks and toilets by hospitals, nursing homes, and other long-term care facilities.  Jeff Donn writes,

In a frustrating quirk in government policy, the most tightly controlled drugs, like painkilling narcotics prone to abuse, are the ones that most often elude environmental regulation when they become waste.

Federal narcotics regulators impose strict rules meant to keep controlled pharmaceuticals out of the wrong hands. Yet those rules also make these drugs nearly impossible to handle safely as waste, say hospital environmental administrators.

Many would like to send controlled substances to landfills or incinerators to keep them out of waterways as much as possible. Instead, they are nearly always dropped into sinks and toilets by hospitals, nursing homes and other long-term care facilities.

The problem is huge, because more than 365 medicines are controlled by the U.S. Drug Enforcement Administration - almost 12 percent of all prescriptions, the agency says. They include widely used narcotics, stimulants, depressants and steroids - drugs like codeine, morphine, oxycodone, diazepam (often sold as Valium) and methylphenidate (often sold as Ritalin).

At Abbott Northwestern Hospital here, nurse Keri Osborne recently was opening a locked room at a spine surgery unit, where a machine must check her fingerprints before she pours unused controlled drugs into the sink.

"Back pain, so there's a lot of narcotics here," she explains. Much of the waste consists of liquid in syringes that aren't completely emptied when used to treat patients.

Though a leader in incinerating drug waste, this hospital still puts four gallons of controlled substances down the drain each year, says hazardous waste manager Steven Waderich.

It would be very expensive to do otherwise. "Managing controlled substances, the cost goes up just through the roof," he says.

In nearby Robbinsdale, North Memorial Medical Center pours 50 gallons of controlled substances into its drains annually rather than pay $25,000 to handle and haul it away for safer disposal, says regulated waste coordinator Jerry Fink.

Part of the cost is due to federal rules that state anyone who handles controlled substances, other than a user, must be certified as a police officer or registered with the DEA. That goes for pharmacists, distributors, even waste handlers.

State waste regulators take their cue from federal law and regulations.

Thus, typical assisted-living centers, which are not registered with the DEA, cannot collect unused controlled drugs of residents for offsite disposal.

Even the destruction of controlled drugs must be meticulously documented, so they aren't diverted to addicts. Medical facilities typically send a second staffer to bear witness when controlled substances are poured into sinks or toilets.

Many waste experts now want to rewrite the rules so a broader range of professionals can handle leftover controlled drugs. "And DEA, truth be told, has not been very cooperative and responsive in that regard," says waste consultant Catherine Zimmer at the University of Minnesota.

That could change. The DEA declined requests for an on-the-record interview, but in a statement, spokeswoman Rogene Waite said: "DEA is currently developing regulations to allow for the safe and effective destruction of controlled substances."

Ben Grumbles, the Environmental Protection Agency's water administrator, confirmed his agency has participated in these discussions. He would not provide details, but called the talks productive.