Alicia Ault

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency.

But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency.

But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency.

But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing sponsored by the agency.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said, noting that the FDA will issue a new drug code (NDC) number for a product even if it was never approved. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

Those initially flagged for attention include products that are potentially hazardous, lack evidence of effectiveness, or appear to be fraudulent.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some manufacturers' levothyroxine and phenobarbital products.

“While we want to ensure continued patient access to necessary treatments, as a physician I feel strongly that patients expect and deserve all their prescription medicines to be FDA approved,” said Dr. Andrew C. von Eschenbach, acting FDA commissioner, in a statement.

The agency estimates that less than 2% of prescription drugs have not received its imprimatur. That still means potentially thousands of products that aren't approved.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

Go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing sponsored by the agency.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said, noting that the FDA will issue a new drug code (NDC) number for a product even if it was never approved. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

Those initially flagged for attention include products that are potentially hazardous, lack evidence of effectiveness, or appear to be fraudulent.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some manufacturers' levothyroxine and phenobarbital products.

“While we want to ensure continued patient access to necessary treatments, as a physician I feel strongly that patients expect and deserve all their prescription medicines to be FDA approved,” said Dr. Andrew C. von Eschenbach, acting FDA commissioner, in a statement.

The agency estimates that less than 2% of prescription drugs have not received its imprimatur. That still means potentially thousands of products that aren't approved.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

Go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing sponsored by the agency.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said, noting that the FDA will issue a new drug code (NDC) number for a product even if it was never approved. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

Those initially flagged for attention include products that are potentially hazardous, lack evidence of effectiveness, or appear to be fraudulent.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some manufacturers' levothyroxine and phenobarbital products.

“While we want to ensure continued patient access to necessary treatments, as a physician I feel strongly that patients expect and deserve all their prescription medicines to be FDA approved,” said Dr. Andrew C. von Eschenbach, acting FDA commissioner, in a statement.

The agency estimates that less than 2% of prescription drugs have not received its imprimatur. That still means potentially thousands of products that aren't approved.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

Go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

BOSTON — Resection of at least 15 nodes improves colon cancer survival at all stages, according to a study presented by Dr. Steven L. Chen at the annual meeting of the American Surgical Association.

The existence of nodal metastases is the most important prognostic factor for colon cancer, and guidelines on how many nodes to sample range anywhere from 7 to 40, said Dr. Chen, adding that the national median is 9.

Dr. Chen, who is in private practice in Santa Monica, Calif., and his colleague Dr. Anton J. Bilchik of the John Wayne Cancer Institute, Santa Monica, theorized that increasing the number of lymph nodes sampled—to at least 15—would improve survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers looked at 82,892 colon cancer patients who had resections during 1998–2000. The mean number of nodes sampled was 9. Only 26% had more than 15 nodes sampled.

Using a multivariate analysis, the researchers determined survival by stage. For stage I patients with 0 nodes harvested, median survival was 132 months; for 1–7 nodes, it was 138 months; for 8–14 nodes, it was 131 months; and for more than 15 nodes, 149 months. Stage II survival was 45 months for 0 nodes; 77 months for 1–7 nodes; 99 months for 8–14 nodes; and 131 months for more than 15 nodes. Survival for stage III was 46 months for 1–7 nodes; 52 months for 8–14 nodes; and 67 months for more than 15.

Overall, when more than 15 nodes were harvested, stage I patients gained 11 months; stage II patients, 54 months; and stage III patients, 21 months, compared with harvesting 1–7 nodes.

The number of nodes harvested seemed to be one of the biggest factors affecting survival, partly because it made it more likely to find cancer, said Dr. Chen. The study also showed that node harvest is a proxy measure for quality of care, he said.

Dr. Heidi Nelson, chief of the division of colon and rectal surgery at the Mayo Medical School, Rochester, Minn., agreed that lymph node resection does reflect surgical quality. She suggested that more needed to be done to increase awareness of the importance of taking more nodes, noting that guidelines issued in 2000 by the College of American Pathologists called for a 12-node harvest.

The National Quality Forum has approved a set of quality measures on breast and colon cancer submitted by the American College of Surgeons' Commission on Cancer, one of which stipulates that the surgical specimen include 12 nodes, said Dr. R. Scott Jones, chairman of the department of surgery at the University of Virginia, Charlottesville. Dr. Jones said in an interview that some health insurance companies “are now accepting the evidence that the number of lymph nodes removed during operations for colon/rectal cancer constitute an important measure of the quality of care.” He said that at least one major insurer—which he declined to identify—has notified surgeons that the company will monitor their nodal harvest.

Dr. Jones noted that Dr. Chen and Dr. Bilchik's study is one of the first to show that the number of nodes removed significantly increases survival. With these new findings and the proposed quality measures, Dr. Jones expects “a rather remarkable increase in the number of lymph nodes reported in surgical specimens in the next few years.”

“Obviously, more work needs to be done,” said Dr. Chen. In the meantime, he believes that at least 15 nodes should be taken. “I think this is a quality measure worth tracking,” said Dr. Chen.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Resection of at least 15 nodes improves colon cancer survival at all stages, according to a study presented by Dr. Steven L. Chen at the annual meeting of the American Surgical Association.

The existence of nodal metastases is the most important prognostic factor for colon cancer, and guidelines on how many nodes to sample range anywhere from 7 to 40, said Dr. Chen, adding that the national median is 9.

Dr. Chen, who is in private practice in Santa Monica, Calif., and his colleague Dr. Anton J. Bilchik of the John Wayne Cancer Institute, Santa Monica, theorized that increasing the number of lymph nodes sampled—to at least 15—would improve survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers looked at 82,892 colon cancer patients who had resections during 1998–2000. The mean number of nodes sampled was 9. Only 26% had more than 15 nodes sampled.

Using a multivariate analysis, the researchers determined survival by stage. For stage I patients with 0 nodes harvested, median survival was 132 months; for 1–7 nodes, it was 138 months; for 8–14 nodes, it was 131 months; and for more than 15 nodes, 149 months. Stage II survival was 45 months for 0 nodes; 77 months for 1–7 nodes; 99 months for 8–14 nodes; and 131 months for more than 15 nodes. Survival for stage III was 46 months for 1–7 nodes; 52 months for 8–14 nodes; and 67 months for more than 15.

Overall, when more than 15 nodes were harvested, stage I patients gained 11 months; stage II patients, 54 months; and stage III patients, 21 months, compared with harvesting 1–7 nodes.

The number of nodes harvested seemed to be one of the biggest factors affecting survival, partly because it made it more likely to find cancer, said Dr. Chen. The study also showed that node harvest is a proxy measure for quality of care, he said.

Dr. Heidi Nelson, chief of the division of colon and rectal surgery at the Mayo Medical School, Rochester, Minn., agreed that lymph node resection does reflect surgical quality. She suggested that more needed to be done to increase awareness of the importance of taking more nodes, noting that guidelines issued in 2000 by the College of American Pathologists called for a 12-node harvest.

The National Quality Forum has approved a set of quality measures on breast and colon cancer submitted by the American College of Surgeons' Commission on Cancer, one of which stipulates that the surgical specimen include 12 nodes, said Dr. R. Scott Jones, chairman of the department of surgery at the University of Virginia, Charlottesville. Dr. Jones said in an interview that some health insurance companies “are now accepting the evidence that the number of lymph nodes removed during operations for colon/rectal cancer constitute an important measure of the quality of care.” He said that at least one major insurer—which he declined to identify—has notified surgeons that the company will monitor their nodal harvest.

Dr. Jones noted that Dr. Chen and Dr. Bilchik's study is one of the first to show that the number of nodes removed significantly increases survival. With these new findings and the proposed quality measures, Dr. Jones expects “a rather remarkable increase in the number of lymph nodes reported in surgical specimens in the next few years.”

“Obviously, more work needs to be done,” said Dr. Chen. In the meantime, he believes that at least 15 nodes should be taken. “I think this is a quality measure worth tracking,” said Dr. Chen.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON — Resection of at least 15 nodes improves colon cancer survival at all stages, according to a study presented by Dr. Steven L. Chen at the annual meeting of the American Surgical Association.

The existence of nodal metastases is the most important prognostic factor for colon cancer, and guidelines on how many nodes to sample range anywhere from 7 to 40, said Dr. Chen, adding that the national median is 9.

Dr. Chen, who is in private practice in Santa Monica, Calif., and his colleague Dr. Anton J. Bilchik of the John Wayne Cancer Institute, Santa Monica, theorized that increasing the number of lymph nodes sampled—to at least 15—would improve survival. Using the Surveillance, Epidemiology, and End Results (SEER) database, the researchers looked at 82,892 colon cancer patients who had resections during 1998–2000. The mean number of nodes sampled was 9. Only 26% had more than 15 nodes sampled.

Using a multivariate analysis, the researchers determined survival by stage. For stage I patients with 0 nodes harvested, median survival was 132 months; for 1–7 nodes, it was 138 months; for 8–14 nodes, it was 131 months; and for more than 15 nodes, 149 months. Stage II survival was 45 months for 0 nodes; 77 months for 1–7 nodes; 99 months for 8–14 nodes; and 131 months for more than 15 nodes. Survival for stage III was 46 months for 1–7 nodes; 52 months for 8–14 nodes; and 67 months for more than 15.

Overall, when more than 15 nodes were harvested, stage I patients gained 11 months; stage II patients, 54 months; and stage III patients, 21 months, compared with harvesting 1–7 nodes.

The number of nodes harvested seemed to be one of the biggest factors affecting survival, partly because it made it more likely to find cancer, said Dr. Chen. The study also showed that node harvest is a proxy measure for quality of care, he said.

Dr. Heidi Nelson, chief of the division of colon and rectal surgery at the Mayo Medical School, Rochester, Minn., agreed that lymph node resection does reflect surgical quality. She suggested that more needed to be done to increase awareness of the importance of taking more nodes, noting that guidelines issued in 2000 by the College of American Pathologists called for a 12-node harvest.

The National Quality Forum has approved a set of quality measures on breast and colon cancer submitted by the American College of Surgeons' Commission on Cancer, one of which stipulates that the surgical specimen include 12 nodes, said Dr. R. Scott Jones, chairman of the department of surgery at the University of Virginia, Charlottesville. Dr. Jones said in an interview that some health insurance companies “are now accepting the evidence that the number of lymph nodes removed during operations for colon/rectal cancer constitute an important measure of the quality of care.” He said that at least one major insurer—which he declined to identify—has notified surgeons that the company will monitor their nodal harvest.

Dr. Jones noted that Dr. Chen and Dr. Bilchik's study is one of the first to show that the number of nodes removed significantly increases survival. With these new findings and the proposed quality measures, Dr. Jones expects “a rather remarkable increase in the number of lymph nodes reported in surgical specimens in the next few years.”

“Obviously, more work needs to be done,” said Dr. Chen. In the meantime, he believes that at least 15 nodes should be taken. “I think this is a quality measure worth tracking,” said Dr. Chen.

ELSEVIER GLOBAL MEDICAL NEWS

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some levothyroxine and phenobarbital products.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

The agency recently announced that it is requiring makers of carbinoxamine-containing products to seek approval by late September. Any unapproved products still on the shelves at that date will be ordered off the market, said Deborah M. Autor, FDA associate director for compliance policy. Carbinoxamine is used in cough and cold treatments, mostly for children, that have been associated with 21 reported deaths since 1983.

Interested parties can go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some levothyroxine and phenobarbital products.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

The agency recently announced that it is requiring makers of carbinoxamine-containing products to seek approval by late September. Any unapproved products still on the shelves at that date will be ordered off the market, said Deborah M. Autor, FDA associate director for compliance policy. Carbinoxamine is used in cough and cold treatments, mostly for children, that have been associated with 21 reported deaths since 1983.

Interested parties can go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

The Food and Drug Administration announced that it is renewing efforts to ensure that all drugs currently sold by prescription either go through its formal approval process or be taken off the market.

The agency has periodically targeted some of these products using its existing authority. Now, the FDA has issued more formal guidance that spells out for manufacturers how it will prioritize enforcement, and what route they can take to prove safety and efficacy of their products.

There are many reasons why unapproved products are on the market, said Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, at a press briefing.

Most were marketed before passage of the 1962 Food, Drug, and Cosmetic Act, which required formal proof of safety and efficacy. Or their makers may simply have begun selling the products without seeking the agency's approval, he said. In very few cases, the products are grandfathered in under existing laws, agency officials said.

Many of the unapproved drugs are listed in the Physicians' Desk Reference. Some are advertised in medical journals.

If the manufacturers don't seek approval, they will be subject to enforcement action, Dr. Galson said. But in most cases, the FDA will not remove a drug from the market if it has been shown to have some medical utility. Examples include some levothyroxine and phenobarbital products.

Many of the drugs are cough and cold preparations that include pheniramine maleate and dexbrompheniramine maleate, or single-ingredient narcotics such as codeine phosphate and oxycodone HCl. Sedatives like chloral hydrate are also unapproved.

The agency recently announced that it is requiring makers of carbinoxamine-containing products to seek approval by late September. Any unapproved products still on the shelves at that date will be ordered off the market, said Deborah M. Autor, FDA associate director for compliance policy. Carbinoxamine is used in cough and cold treatments, mostly for children, that have been associated with 21 reported deaths since 1983.

Interested parties can go to the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda

BALTIMORE — The incidence of pulmonary arterial hypertension is widely underestimated, but with better diagnostic tools and more treatments, rheumatologists and others can intervene earlier in the disease process, said Dr. Hunter Champion at a cardiovascular conference sponsored by Johns Hopkins University, Baltimore.

There are 1–2 million cases of pulmonary arterial hypertension (PAH) a year, primarily affecting women and usually striking people in their 40s. But PAH is on the rise, said Dr. Champion of the university.

Hospitalizations for PAH tripled from 1980 to 2002, when they hit 260,000, according to the National Hospital Discharge Survey (www.cdc.gov/mmwr/preview/mmwrhtml/ss5405a1.htm#tab10

Suspect PAH if there is a loud pulmonic closure, right ventricular lift, systolic murmur (tricuspid regurgitation), diastolic murmur (pulmonary regurgitation), or right ventricular presystolic gallop. A family history of PAH, connective tissue disease, congenital heart disease, portal hypertension, a history of deep vein thrombosis or pulmonary embolism, human immunodeficiency virus, and appetite-suppressant use are all risk factors, Dr. Champion said.

Symptoms usually include dyspnea, angina, syncope, edema, and Raynaud's phenomenon. PAH is often misdiagnosed as coronary artery disease (CAD), heart rhythm disorder, asthma, or, sometimes, a psychiatric condition such as panic disorder, he said.

Diagnostics should be done to rule out HIV, emphysema, sleep disorder, CAD, and autoantibody disorders such as systemic lupus erythematosus.

A right heart catheterization is critical, he said. “Until you have that, you don't really have a handle on what's going on.”

The catheterization also will give a reading on pulmonary artery pressure and response to vasodilators, both of which help determine a therapeutic strategy.

PAH arises through the endothelin, nitric oxide, and prostacyclin pathways. Three prostacyclin analogues are the most commonly used therapies: epoprostenol (Flolan), treprostinil (Remodulin), and iloprost (Ventavis). The drugs are expensive—$60,000–$100,000 a year—and have drawbacks, including jaw, leg, and site pain (for epoprostenol, which is delivered through an in-dwelling catheter), and risk of infection and thrombocytopenia. With epoprostenol, rebound PAH is common, he said.

Bosentan (Tracleer) acts on the endothelin pathway. The oral medication has been shown to delay PAH progression, although it is still considered palliative. It has a high risk of teratogenicity, which is important to consider because many PAH patients are women in their childbearing years.

Liver damage is also a continuing concern. The Food and Drug Administration recently strengthened hepatotoxicity warnings and emphasized the need to conduct monthly liver function tests. Bosentan is also expensive: $36,000 a year.

Two new therapies are considered promising for treating PAH, they include Sitaxsentan, which was recently designated as approvable by the FDA, and ambrisentan, which is close to market. Both are type-A selective endothelin receptor antagonists.

Sildenafil (Viagra) has been shown to improve patient functioning, as demonstrated by the 6-minute walking test. Dr. Champion said he was impressed with the drug's ability to convert patients from class IV to class III status or from class III to class II. The phosphodiesterase 5 inhibitor is marketed as Revatio for PAH. It is the lowest-priced therapy, at about $9,800 a year.

Lung transplantation is a possibility for advanced PAH, but a recent change in United Network for Organ Sharing rules has lengthened patients' wait, Dr. Champion said. “It is the option of last resort but certainly is necessary,” he said.

BALTIMORE — The incidence of pulmonary arterial hypertension is widely underestimated, but with better diagnostic tools and more treatments, rheumatologists and others can intervene earlier in the disease process, said Dr. Hunter Champion at a cardiovascular conference sponsored by Johns Hopkins University, Baltimore.

There are 1–2 million cases of pulmonary arterial hypertension (PAH) a year, primarily affecting women and usually striking people in their 40s. But PAH is on the rise, said Dr. Champion of the university.

Hospitalizations for PAH tripled from 1980 to 2002, when they hit 260,000, according to the National Hospital Discharge Survey (www.cdc.gov/mmwr/preview/mmwrhtml/ss5405a1.htm#tab10

Suspect PAH if there is a loud pulmonic closure, right ventricular lift, systolic murmur (tricuspid regurgitation), diastolic murmur (pulmonary regurgitation), or right ventricular presystolic gallop. A family history of PAH, connective tissue disease, congenital heart disease, portal hypertension, a history of deep vein thrombosis or pulmonary embolism, human immunodeficiency virus, and appetite-suppressant use are all risk factors, Dr. Champion said.

Symptoms usually include dyspnea, angina, syncope, edema, and Raynaud's phenomenon. PAH is often misdiagnosed as coronary artery disease (CAD), heart rhythm disorder, asthma, or, sometimes, a psychiatric condition such as panic disorder, he said.

Diagnostics should be done to rule out HIV, emphysema, sleep disorder, CAD, and autoantibody disorders such as systemic lupus erythematosus.

A right heart catheterization is critical, he said. “Until you have that, you don't really have a handle on what's going on.”

The catheterization also will give a reading on pulmonary artery pressure and response to vasodilators, both of which help determine a therapeutic strategy.

PAH arises through the endothelin, nitric oxide, and prostacyclin pathways. Three prostacyclin analogues are the most commonly used therapies: epoprostenol (Flolan), treprostinil (Remodulin), and iloprost (Ventavis). The drugs are expensive—$60,000–$100,000 a year—and have drawbacks, including jaw, leg, and site pain (for epoprostenol, which is delivered through an in-dwelling catheter), and risk of infection and thrombocytopenia. With epoprostenol, rebound PAH is common, he said.

Bosentan (Tracleer) acts on the endothelin pathway. The oral medication has been shown to delay PAH progression, although it is still considered palliative. It has a high risk of teratogenicity, which is important to consider because many PAH patients are women in their childbearing years.

Liver damage is also a continuing concern. The Food and Drug Administration recently strengthened hepatotoxicity warnings and emphasized the need to conduct monthly liver function tests. Bosentan is also expensive: $36,000 a year.

Two new therapies are considered promising for treating PAH, they include Sitaxsentan, which was recently designated as approvable by the FDA, and ambrisentan, which is close to market. Both are type-A selective endothelin receptor antagonists.

Sildenafil (Viagra) has been shown to improve patient functioning, as demonstrated by the 6-minute walking test. Dr. Champion said he was impressed with the drug's ability to convert patients from class IV to class III status or from class III to class II. The phosphodiesterase 5 inhibitor is marketed as Revatio for PAH. It is the lowest-priced therapy, at about $9,800 a year.

Lung transplantation is a possibility for advanced PAH, but a recent change in United Network for Organ Sharing rules has lengthened patients' wait, Dr. Champion said. “It is the option of last resort but certainly is necessary,” he said.

BALTIMORE — The incidence of pulmonary arterial hypertension is widely underestimated, but with better diagnostic tools and more treatments, rheumatologists and others can intervene earlier in the disease process, said Dr. Hunter Champion at a cardiovascular conference sponsored by Johns Hopkins University, Baltimore.

There are 1–2 million cases of pulmonary arterial hypertension (PAH) a year, primarily affecting women and usually striking people in their 40s. But PAH is on the rise, said Dr. Champion of the university.

Hospitalizations for PAH tripled from 1980 to 2002, when they hit 260,000, according to the National Hospital Discharge Survey (www.cdc.gov/mmwr/preview/mmwrhtml/ss5405a1.htm#tab10

Suspect PAH if there is a loud pulmonic closure, right ventricular lift, systolic murmur (tricuspid regurgitation), diastolic murmur (pulmonary regurgitation), or right ventricular presystolic gallop. A family history of PAH, connective tissue disease, congenital heart disease, portal hypertension, a history of deep vein thrombosis or pulmonary embolism, human immunodeficiency virus, and appetite-suppressant use are all risk factors, Dr. Champion said.

Symptoms usually include dyspnea, angina, syncope, edema, and Raynaud's phenomenon. PAH is often misdiagnosed as coronary artery disease (CAD), heart rhythm disorder, asthma, or, sometimes, a psychiatric condition such as panic disorder, he said.

Diagnostics should be done to rule out HIV, emphysema, sleep disorder, CAD, and autoantibody disorders such as systemic lupus erythematosus.

A right heart catheterization is critical, he said. “Until you have that, you don't really have a handle on what's going on.”

The catheterization also will give a reading on pulmonary artery pressure and response to vasodilators, both of which help determine a therapeutic strategy.

PAH arises through the endothelin, nitric oxide, and prostacyclin pathways. Three prostacyclin analogues are the most commonly used therapies: epoprostenol (Flolan), treprostinil (Remodulin), and iloprost (Ventavis). The drugs are expensive—$60,000–$100,000 a year—and have drawbacks, including jaw, leg, and site pain (for epoprostenol, which is delivered through an in-dwelling catheter), and risk of infection and thrombocytopenia. With epoprostenol, rebound PAH is common, he said.

Bosentan (Tracleer) acts on the endothelin pathway. The oral medication has been shown to delay PAH progression, although it is still considered palliative. It has a high risk of teratogenicity, which is important to consider because many PAH patients are women in their childbearing years.

Liver damage is also a continuing concern. The Food and Drug Administration recently strengthened hepatotoxicity warnings and emphasized the need to conduct monthly liver function tests. Bosentan is also expensive: $36,000 a year.

Two new therapies are considered promising for treating PAH, they include Sitaxsentan, which was recently designated as approvable by the FDA, and ambrisentan, which is close to market. Both are type-A selective endothelin receptor antagonists.

Sildenafil (Viagra) has been shown to improve patient functioning, as demonstrated by the 6-minute walking test. Dr. Champion said he was impressed with the drug's ability to convert patients from class IV to class III status or from class III to class II. The phosphodiesterase 5 inhibitor is marketed as Revatio for PAH. It is the lowest-priced therapy, at about $9,800 a year.

Lung transplantation is a possibility for advanced PAH, but a recent change in United Network for Organ Sharing rules has lengthened patients' wait, Dr. Champion said. “It is the option of last resort but certainly is necessary,” he said.

Lipitor Personal Injury Suits

The top-selling statin Lipitor (atorvastatin) is being blamed for causing a suicide, peripheral neuropathy, memory loss, and severe muscle damage in two suits filed against the drug's maker, Pfizer Inc., by a New York-based plaintiff's attorney, Mark Jay Krum. The complaint, filed in New York State Supreme Court, alleges that after using Lipitor for 17 months, 60-year-old Charles M. Wilson experienced peripheral neuropathy, inflammatory demyelinating polyneuropathy, and memory loss. Three years after ceasing the medication, Mr. Wilson still has loss of balance, fatigue, and burning in his extremities, according to the suit. In the second case, 47-year-old Michael Mazzariello claimed that Lipitor use led to neuropathy, weakness in his extremities, and short-term memory loss. Both suits claim that Pfizer failed to adequately warn physicians and patients about the drug's risks. At a press briefing, another potential plaintiff alleged that Lipitor caused her teenage son to commit suicide. Pfizer said in a statement that it would “vigorously challenge in court all the baseless claims made in these lawsuits.”

Guidant Price Disclosure Sought

Advocacy group Public Citizen has filed a lawsuit in Pennsylvania federal court seeking to force the medical device maker Guidant Inc. to disclose its prices to ECRI, a nonprofit organization that collects cost-effectiveness and safety data on procedures and devices for hospitals, group purchasing organizations, health plans, and health agencies worldwide. ECRI has published a database of cardiac rhythm management devices since 1996. In 2001, Guidant, a division of Boston Scientific, began requiring customers to keep prices confidential. ECRI continued to publish the data because it was not aware of the contractual agreement, according to the suit. After several years of silence, Guidant contacted ECRI in 2004 and asked it to immediately stop publishing the data and urged hospitals to stop supplying information—demands that have been made repeatedly under threat of litigation. The Public Citizen complaint was filed in response and alleges that ECRI's database is noncommercial speech that is protected by the First Amendment. Boston Scientific said confidentiality is an accepted practice in heart rhythm management and essential to its business. “We simply don't want the price negotiated privately with one hospital based on one set of circumstances used against us in negotiations with another hospital with an entirely different set of circumstances,” said Paul Donovan, Boston Scientific senior vice president of corporate communications, in a statement.

Licensure for Drug Sales Reps?

A proposal making its way through the Massachusetts legislature would require that pharmaceutical company sales representatives be licensed by the state and complete continuing education programs to renew that license. The proposal passed as an amendment to the state budget and was in a joint House-Senate conference report. State Senator Mark C. Montigny, a Democrat from New Bedford, has sought to pass such a licensure requirement several times over the past few years, without success. Under the latest proposal, pharmaceutical companies—and their representatives—would also be prohibited from giving gifts, entertainment, travel, honoraria, or anything of value to physicians or public officials. Violators would be subject to a $5,000 fine and up to 2 years in jail. In a statement, Ken Johnson, senior vice president of the Pharmaceutical Research and Manufacturers Association, said that licensing was unnecessary because the Food and Drug Administration already regulates promotional and educational materials and that the legislation is wrongheaded because it “seeks to impose criminal penalties on what should be viewed as the important sharing of information between pharmaceutical companies and physicians regarding the risks and benefits of medicines.”

Survey: FDA Influenced by Politics

A majority of Americans—82%—believe the FDA is greatly influenced by politics when making decisions about the safety and efficacy of new prescription drugs, according to a Wall Street Journal online Harris Interactive poll. The finding was similar across parties, with 87% of Democrats, 77% of Republicans, and 88% of Independents saying they thought that politics outweighed science greatly or to some extent in decision making. The survey of more than 2,300 adults was conducted in mid-May. In addition, almost 60% said the agency is doing a fair or poor job in ensuring the safety and efficacy of new drugs. Only 36% said it was doing an excellent or good job. That is a reversal from 2 years ago, when 56% had a positive view and 37% a negative view of the FDA. Opinions have not changed much on the agency's performance in bringing innovative drugs to market quickly. In 2004, 62% said the FDA was not doing well on that front, compared with 70% in the latest poll.

Lipitor Personal Injury Suits

The top-selling statin Lipitor (atorvastatin) is being blamed for causing a suicide, peripheral neuropathy, memory loss, and severe muscle damage in two suits filed against the drug's maker, Pfizer Inc., by a New York-based plaintiff's attorney, Mark Jay Krum. The complaint, filed in New York State Supreme Court, alleges that after using Lipitor for 17 months, 60-year-old Charles M. Wilson experienced peripheral neuropathy, inflammatory demyelinating polyneuropathy, and memory loss. Three years after ceasing the medication, Mr. Wilson still has loss of balance, fatigue, and burning in his extremities, according to the suit. In the second case, 47-year-old Michael Mazzariello claimed that Lipitor use led to neuropathy, weakness in his extremities, and short-term memory loss. Both suits claim that Pfizer failed to adequately warn physicians and patients about the drug's risks. At a press briefing, another potential plaintiff alleged that Lipitor caused her teenage son to commit suicide. Pfizer said in a statement that it would “vigorously challenge in court all the baseless claims made in these lawsuits.”

Guidant Price Disclosure Sought

Advocacy group Public Citizen has filed a lawsuit in Pennsylvania federal court seeking to force the medical device maker Guidant Inc. to disclose its prices to ECRI, a nonprofit organization that collects cost-effectiveness and safety data on procedures and devices for hospitals, group purchasing organizations, health plans, and health agencies worldwide. ECRI has published a database of cardiac rhythm management devices since 1996. In 2001, Guidant, a division of Boston Scientific, began requiring customers to keep prices confidential. ECRI continued to publish the data because it was not aware of the contractual agreement, according to the suit. After several years of silence, Guidant contacted ECRI in 2004 and asked it to immediately stop publishing the data and urged hospitals to stop supplying information—demands that have been made repeatedly under threat of litigation. The Public Citizen complaint was filed in response and alleges that ECRI's database is noncommercial speech that is protected by the First Amendment. Boston Scientific said confidentiality is an accepted practice in heart rhythm management and essential to its business. “We simply don't want the price negotiated privately with one hospital based on one set of circumstances used against us in negotiations with another hospital with an entirely different set of circumstances,” said Paul Donovan, Boston Scientific senior vice president of corporate communications, in a statement.

Licensure for Drug Sales Reps?

A proposal making its way through the Massachusetts legislature would require that pharmaceutical company sales representatives be licensed by the state and complete continuing education programs to renew that license. The proposal passed as an amendment to the state budget and was in a joint House-Senate conference report. State Senator Mark C. Montigny, a Democrat from New Bedford, has sought to pass such a licensure requirement several times over the past few years, without success. Under the latest proposal, pharmaceutical companies—and their representatives—would also be prohibited from giving gifts, entertainment, travel, honoraria, or anything of value to physicians or public officials. Violators would be subject to a $5,000 fine and up to 2 years in jail. In a statement, Ken Johnson, senior vice president of the Pharmaceutical Research and Manufacturers Association, said that licensing was unnecessary because the Food and Drug Administration already regulates promotional and educational materials and that the legislation is wrongheaded because it “seeks to impose criminal penalties on what should be viewed as the important sharing of information between pharmaceutical companies and physicians regarding the risks and benefits of medicines.”

Survey: FDA Influenced by Politics

A majority of Americans—82%—believe the FDA is greatly influenced by politics when making decisions about the safety and efficacy of new prescription drugs, according to a Wall Street Journal online Harris Interactive poll. The finding was similar across parties, with 87% of Democrats, 77% of Republicans, and 88% of Independents saying they thought that politics outweighed science greatly or to some extent in decision making. The survey of more than 2,300 adults was conducted in mid-May. In addition, almost 60% said the agency is doing a fair or poor job in ensuring the safety and efficacy of new drugs. Only 36% said it was doing an excellent or good job. That is a reversal from 2 years ago, when 56% had a positive view and 37% a negative view of the FDA. Opinions have not changed much on the agency's performance in bringing innovative drugs to market quickly. In 2004, 62% said the FDA was not doing well on that front, compared with 70% in the latest poll.

Lipitor Personal Injury Suits

The top-selling statin Lipitor (atorvastatin) is being blamed for causing a suicide, peripheral neuropathy, memory loss, and severe muscle damage in two suits filed against the drug's maker, Pfizer Inc., by a New York-based plaintiff's attorney, Mark Jay Krum. The complaint, filed in New York State Supreme Court, alleges that after using Lipitor for 17 months, 60-year-old Charles M. Wilson experienced peripheral neuropathy, inflammatory demyelinating polyneuropathy, and memory loss. Three years after ceasing the medication, Mr. Wilson still has loss of balance, fatigue, and burning in his extremities, according to the suit. In the second case, 47-year-old Michael Mazzariello claimed that Lipitor use led to neuropathy, weakness in his extremities, and short-term memory loss. Both suits claim that Pfizer failed to adequately warn physicians and patients about the drug's risks. At a press briefing, another potential plaintiff alleged that Lipitor caused her teenage son to commit suicide. Pfizer said in a statement that it would “vigorously challenge in court all the baseless claims made in these lawsuits.”

Guidant Price Disclosure Sought

Advocacy group Public Citizen has filed a lawsuit in Pennsylvania federal court seeking to force the medical device maker Guidant Inc. to disclose its prices to ECRI, a nonprofit organization that collects cost-effectiveness and safety data on procedures and devices for hospitals, group purchasing organizations, health plans, and health agencies worldwide. ECRI has published a database of cardiac rhythm management devices since 1996. In 2001, Guidant, a division of Boston Scientific, began requiring customers to keep prices confidential. ECRI continued to publish the data because it was not aware of the contractual agreement, according to the suit. After several years of silence, Guidant contacted ECRI in 2004 and asked it to immediately stop publishing the data and urged hospitals to stop supplying information—demands that have been made repeatedly under threat of litigation. The Public Citizen complaint was filed in response and alleges that ECRI's database is noncommercial speech that is protected by the First Amendment. Boston Scientific said confidentiality is an accepted practice in heart rhythm management and essential to its business. “We simply don't want the price negotiated privately with one hospital based on one set of circumstances used against us in negotiations with another hospital with an entirely different set of circumstances,” said Paul Donovan, Boston Scientific senior vice president of corporate communications, in a statement.

Licensure for Drug Sales Reps?

A proposal making its way through the Massachusetts legislature would require that pharmaceutical company sales representatives be licensed by the state and complete continuing education programs to renew that license. The proposal passed as an amendment to the state budget and was in a joint House-Senate conference report. State Senator Mark C. Montigny, a Democrat from New Bedford, has sought to pass such a licensure requirement several times over the past few years, without success. Under the latest proposal, pharmaceutical companies—and their representatives—would also be prohibited from giving gifts, entertainment, travel, honoraria, or anything of value to physicians or public officials. Violators would be subject to a $5,000 fine and up to 2 years in jail. In a statement, Ken Johnson, senior vice president of the Pharmaceutical Research and Manufacturers Association, said that licensing was unnecessary because the Food and Drug Administration already regulates promotional and educational materials and that the legislation is wrongheaded because it “seeks to impose criminal penalties on what should be viewed as the important sharing of information between pharmaceutical companies and physicians regarding the risks and benefits of medicines.”

Survey: FDA Influenced by Politics

A majority of Americans—82%—believe the FDA is greatly influenced by politics when making decisions about the safety and efficacy of new prescription drugs, according to a Wall Street Journal online Harris Interactive poll. The finding was similar across parties, with 87% of Democrats, 77% of Republicans, and 88% of Independents saying they thought that politics outweighed science greatly or to some extent in decision making. The survey of more than 2,300 adults was conducted in mid-May. In addition, almost 60% said the agency is doing a fair or poor job in ensuring the safety and efficacy of new drugs. Only 36% said it was doing an excellent or good job. That is a reversal from 2 years ago, when 56% had a positive view and 37% a negative view of the FDA. Opinions have not changed much on the agency's performance in bringing innovative drugs to market quickly. In 2004, 62% said the FDA was not doing well on that front, compared with 70% in the latest poll.

A review of New York state's report card on coronary artery bypass graft surgery has found that mortality risks were 50% lower when the procedure was done by higher-performing surgeons or at higher-rated hospitals, compared with those that were done by lower-performing surgeons or at lower-rated facilities.

However, the study authors—Dr. Ashish K. Jha, of the department of health policy and management at the Harvard School of Public Health, Boston, and Arnold Epstein, chair of the department—also found that the reports, whether positive or negative, did not change hospital market share.

“We found no evidence that purchasers or patients are using these reports to drive market share to higher-performing providers,” they wrote (Health Aff. [Millwood]. 2006;25:844–55).

But the data “seemed to have a critical impact on practicing surgeons' livelihood,” wrote Dr. Jha and Dr. Epstein, who also noted that those surgeons who received lower grades were more likely to retire or stop practicing.

The researchers looked at data collected from 1989 to 2002 as part of the New York State Cardiac Surgery Reporting System.

Hospital data, which are reported annually, include risk-adjusted mortality and the number of cases per facility. The mortality data for individual surgeons were available, but only over 3-year periods. The authors were able to identify those surgeons who had dropped out of reporting and they attempted to follow up with all of them either by phone or e-mail.

To analyze the data, the authors divided hospitals and surgeons into four categories: the top decile, top quartile, bottom quartile, and bottom decile. Thirty-three hospitals performed CABG during the study years. Two were excluded because they had less than 3 years' experience.

CABG hospitals were more likely to be teaching facilities, to be located in New York City, and to be larger, with a mean 644 beds, compared with 315 for non-CABG facilities.

During the study period, 168 surgeons performed CABG.

Overall, patients in top-decile hospitals had an average risk-adjusted mortality of 1.59, compared with 2.78 for those in the bottom-decile facilities.

Those patients who were operated on by top-decile surgeons had a risk-adjusted mortality of 1.58, compared with 3.20 for the patients of bottom-decile surgeons.

After the report card was published, 20% of bottom-quartile surgeons quit performing CABG, compared with 5% of those in the top three quartiles; 31 surgeons—with a median age of 61 years—left practice.

Follow-up data were available on 25 of the surgeons (2 others died): 9 were still doing CABG outside of New York, 9 retired, and 7 had taken nonclinical positions. Of the 18 surgeons who had answered survey questions, 10 said that the report card had not influenced their decision.

A review of New York state's report card on coronary artery bypass graft surgery has found that mortality risks were 50% lower when the procedure was done by higher-performing surgeons or at higher-rated hospitals, compared with those that were done by lower-performing surgeons or at lower-rated facilities.

However, the study authors—Dr. Ashish K. Jha, of the department of health policy and management at the Harvard School of Public Health, Boston, and Arnold Epstein, chair of the department—also found that the reports, whether positive or negative, did not change hospital market share.

“We found no evidence that purchasers or patients are using these reports to drive market share to higher-performing providers,” they wrote (Health Aff. [Millwood]. 2006;25:844–55).

But the data “seemed to have a critical impact on practicing surgeons' livelihood,” wrote Dr. Jha and Dr. Epstein, who also noted that those surgeons who received lower grades were more likely to retire or stop practicing.

The researchers looked at data collected from 1989 to 2002 as part of the New York State Cardiac Surgery Reporting System.

Hospital data, which are reported annually, include risk-adjusted mortality and the number of cases per facility. The mortality data for individual surgeons were available, but only over 3-year periods. The authors were able to identify those surgeons who had dropped out of reporting and they attempted to follow up with all of them either by phone or e-mail.

To analyze the data, the authors divided hospitals and surgeons into four categories: the top decile, top quartile, bottom quartile, and bottom decile. Thirty-three hospitals performed CABG during the study years. Two were excluded because they had less than 3 years' experience.

CABG hospitals were more likely to be teaching facilities, to be located in New York City, and to be larger, with a mean 644 beds, compared with 315 for non-CABG facilities.

During the study period, 168 surgeons performed CABG.

Overall, patients in top-decile hospitals had an average risk-adjusted mortality of 1.59, compared with 2.78 for those in the bottom-decile facilities.

Those patients who were operated on by top-decile surgeons had a risk-adjusted mortality of 1.58, compared with 3.20 for the patients of bottom-decile surgeons.

After the report card was published, 20% of bottom-quartile surgeons quit performing CABG, compared with 5% of those in the top three quartiles; 31 surgeons—with a median age of 61 years—left practice.

Follow-up data were available on 25 of the surgeons (2 others died): 9 were still doing CABG outside of New York, 9 retired, and 7 had taken nonclinical positions. Of the 18 surgeons who had answered survey questions, 10 said that the report card had not influenced their decision.

A review of New York state's report card on coronary artery bypass graft surgery has found that mortality risks were 50% lower when the procedure was done by higher-performing surgeons or at higher-rated hospitals, compared with those that were done by lower-performing surgeons or at lower-rated facilities.

However, the study authors—Dr. Ashish K. Jha, of the department of health policy and management at the Harvard School of Public Health, Boston, and Arnold Epstein, chair of the department—also found that the reports, whether positive or negative, did not change hospital market share.

“We found no evidence that purchasers or patients are using these reports to drive market share to higher-performing providers,” they wrote (Health Aff. [Millwood]. 2006;25:844–55).

But the data “seemed to have a critical impact on practicing surgeons' livelihood,” wrote Dr. Jha and Dr. Epstein, who also noted that those surgeons who received lower grades were more likely to retire or stop practicing.

The researchers looked at data collected from 1989 to 2002 as part of the New York State Cardiac Surgery Reporting System.

Hospital data, which are reported annually, include risk-adjusted mortality and the number of cases per facility. The mortality data for individual surgeons were available, but only over 3-year periods. The authors were able to identify those surgeons who had dropped out of reporting and they attempted to follow up with all of them either by phone or e-mail.

To analyze the data, the authors divided hospitals and surgeons into four categories: the top decile, top quartile, bottom quartile, and bottom decile. Thirty-three hospitals performed CABG during the study years. Two were excluded because they had less than 3 years' experience.

CABG hospitals were more likely to be teaching facilities, to be located in New York City, and to be larger, with a mean 644 beds, compared with 315 for non-CABG facilities.

During the study period, 168 surgeons performed CABG.

Overall, patients in top-decile hospitals had an average risk-adjusted mortality of 1.59, compared with 2.78 for those in the bottom-decile facilities.

Those patients who were operated on by top-decile surgeons had a risk-adjusted mortality of 1.58, compared with 3.20 for the patients of bottom-decile surgeons.

After the report card was published, 20% of bottom-quartile surgeons quit performing CABG, compared with 5% of those in the top three quartiles; 31 surgeons—with a median age of 61 years—left practice.

Follow-up data were available on 25 of the surgeons (2 others died): 9 were still doing CABG outside of New York, 9 retired, and 7 had taken nonclinical positions. Of the 18 surgeons who had answered survey questions, 10 said that the report card had not influenced their decision.

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency. But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

Physicians, patients, and pharmacists can continue to check the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency. But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

Physicians, patients, and pharmacists can continue to check the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm

As part of a wider crackdown on the marketing of unapproved drugs, the Food and Drug Administration has notified manufacturers of many unapproved carbinoxamine-containing products that they must submit safety and efficacy data by September or be subject to enforcement action, which could include a forced recall.

The FDA said it was targeting carbinoxamine because of safety concerns, including 21 deaths since 1983 in children under age 2 that may be related to the ingredient. Infants and young children are vulnerable to adverse events with products containing the drug because there are so many different strengths, formulations, and combinations of active ingredients, according to the FDA.

Carbinoxamine, a sedating antihistamine, was first marketed in 1953. Four products are FDA-approved to treat allergic reactions: Palgic Carbinoxamine Maleate Oral Solution (4 mg/5 mL), PamLab LLC; Palgic Carbinoxamine Maleate Tablets (4 mg), PamLab LLC; Carbinox Maleate Solution, Physicians Total Care; and Palgic Carbinoxamine Maleate Tablets USP (4 mg), Physicians Total Care. All four are manufactured by Mikart Inc. of Atlanta, and were approved in 2003.

“We are satisfied that [these products] meet the FDA approval requirements,” said Deborah M. Autor, FDA associate director for compliance policy, at a press briefing sponsored by the agency. But as many as 120 carbinoxamine-containing drugs are being marketed without the agency's approval, Ms. Autor said, adding that there may be more not listed with the FDA.

Many are sold as prescription cough and cold formulations, but the FDA has not found carbinoxamine to be safe or effective for that indication. And they are often labeled for use in children under age 2, even as young as 1–3 months, said the agency.

Under the new directive, unapproved carbinoxamine products will be allowed to stay on pharmacy shelves through September, said Ms. Autor. But the companies must submit new drug applications by that time.

Before prescribing an unapproved carbinoxamine preparation, physicians should consider the patient's medical condition, previous response to the drug, and whether approved alternatives might be more suitable, according to the FDA.

Physicians, patients, and pharmacists can continue to check the FDA's Web site (www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm

WASHINGTON — This winter's flu season is still months away, but officials from the federal government and the American Medical Association say they will be strongly urging physicians to extend influenza vaccine administration beyond its traditional October-December timeframe.

The goal is to protect more Americans and to ensure a more even supply throughout the season.

The effort comes at a time when the vaccine supply is expected to be the largest in U.S. history, with at least 100 million doses slated to be available.

Centers for Disease Control and Prevention and AMA officials discussed their plans at a press briefing sponsored by the National Foundation for Infectious Diseases.

The two organizations began formulating strategies for encouraging a longer vaccination season at the National Influenza Vaccine Summit in January. They and other stakeholders were slated to meet again in late June. With several more high-risk groups targeted for vaccination this year—the CDC has defined 12 target groups—it is getting more difficult for physicians to determine how much vaccine to order and how to effectively manage supply, said Nicole M. Smith, Ph.D., of the CDC's Influenza Division.

There are other barriers to convincing physicians to preorder more vaccine: Any unused supply is essentially “money down the drain,” said Dr. Ardis D. Hoven, medical director of the Bluegrass Care Clinic at the University of Kentucky, Lexington, and a member of the AMA's Board of Trustees. The CDC recommendations encompass about 180 million Americans, said Dr. Hoven.

In most years, vaccination peaks in early October, when about 70% of the vaccine supply has been released, according to CDC data. The demand drops off steeply, usually completely, by late December, which means that most years as much as 30% of the supply goes unused.

Dr. William Schaffner, chairman of the preventive medicine department at Vanderbilt University, Nashville, Tenn., and an NFID board member said that both physicians and patients have fallen into the habit of thinking that if they haven't gotten a shot by late November, they don't need to bother. But he and other officials noted that flu usually peaks in February or March. “We need to persuade them it's not too late to get vaccinated,” Dr. Schaffner said at the briefing.

Physicians have to do some public relations work on their own to make patients aware of this, Dr. Hoven agreed.

And physicians have to be persistent with distributors, she added in an interview. They have “to be more proactive in constantly saying 'When am I getting my doses?,'” she said.

That might not be an easy job. The Health Industry Distributors Association estimates that there are 600 companies that distribute vaccine from two of the three major manufacturers. GlaxoSmithKline, which will have a projected 47 million doses this fall, sells directly only. An estimated 50 million doses will be produced by Sanofi Pasteur. MedImmune Inc. is slated to produce 3 million doses of its live, attenuated nasal vaccine, FluMist. Another 15–20 million doses might become available if the Food and Drug Administration approves a new vaccine from ID Biomedical, which GlaxoSmithKline also owns.

Moreover, the CDC is looking into ways to track the supply so that it can easily locate available doses for physicians, said Dr. Hoven.

Dr. Schaffner said the ramping up of the supply “bodes very well for our attempt to provide protection,” and seems to reflect manufacturers' belief that the market is going to grow.

Physicians and other health care providers are still lagging when it comes to leading by example. Several recent surveys conducted by the AMA and the CDC indicate that only about 40% of health care workers get a flu shot. Dr. Hoven said that often physicians delay getting a shot because they're too busy or want to save the dose for their patients. But she said it's a failing that needs to be corrected.

“In the past, I think health care workers failed to see a connection between themselves and patients they served,” Dr. Hoven said. “So now we say this is something you really need to do for your patients-not for yourself, but for your patients.”

In the future, hospitals might have an incentive to make sure workers are vaccinated. The Joint Commission on Accreditation of Healthcare Organizations has proposed requiring accredited organizations to at least offer immunization to staff, volunteers, and others who have close patient contact. JCAHO is weighing whether to make such an infection control standard mandatory.

WASHINGTON — This winter's flu season is still months away, but officials from the federal government and the American Medical Association say they will be strongly urging physicians to extend influenza vaccine administration beyond its traditional October-December timeframe.

The goal is to protect more Americans and to ensure a more even supply throughout the season.

The effort comes at a time when the vaccine supply is expected to be the largest in U.S. history, with at least 100 million doses slated to be available.

Centers for Disease Control and Prevention and AMA officials discussed their plans at a press briefing sponsored by the National Foundation for Infectious Diseases.

The two organizations began formulating strategies for encouraging a longer vaccination season at the National Influenza Vaccine Summit in January. They and other stakeholders were slated to meet again in late June. With several more high-risk groups targeted for vaccination this year—the CDC has defined 12 target groups—it is getting more difficult for physicians to determine how much vaccine to order and how to effectively manage supply, said Nicole M. Smith, Ph.D., of the CDC's Influenza Division.

There are other barriers to convincing physicians to preorder more vaccine: Any unused supply is essentially “money down the drain,” said Dr. Ardis D. Hoven, medical director of the Bluegrass Care Clinic at the University of Kentucky, Lexington, and a member of the AMA's Board of Trustees. The CDC recommendations encompass about 180 million Americans, said Dr. Hoven.

In most years, vaccination peaks in early October, when about 70% of the vaccine supply has been released, according to CDC data. The demand drops off steeply, usually completely, by late December, which means that most years as much as 30% of the supply goes unused.

Dr. William Schaffner, chairman of the preventive medicine department at Vanderbilt University, Nashville, Tenn., and an NFID board member said that both physicians and patients have fallen into the habit of thinking that if they haven't gotten a shot by late November, they don't need to bother. But he and other officials noted that flu usually peaks in February or March. “We need to persuade them it's not too late to get vaccinated,” Dr. Schaffner said at the briefing.

Physicians have to do some public relations work on their own to make patients aware of this, Dr. Hoven agreed.

And physicians have to be persistent with distributors, she added in an interview. They have “to be more proactive in constantly saying 'When am I getting my doses?,'” she said.

That might not be an easy job. The Health Industry Distributors Association estimates that there are 600 companies that distribute vaccine from two of the three major manufacturers. GlaxoSmithKline, which will have a projected 47 million doses this fall, sells directly only. An estimated 50 million doses will be produced by Sanofi Pasteur. MedImmune Inc. is slated to produce 3 million doses of its live, attenuated nasal vaccine, FluMist. Another 15–20 million doses might become available if the Food and Drug Administration approves a new vaccine from ID Biomedical, which GlaxoSmithKline also owns.

Moreover, the CDC is looking into ways to track the supply so that it can easily locate available doses for physicians, said Dr. Hoven.

Dr. Schaffner said the ramping up of the supply “bodes very well for our attempt to provide protection,” and seems to reflect manufacturers' belief that the market is going to grow.

Physicians and other health care providers are still lagging when it comes to leading by example. Several recent surveys conducted by the AMA and the CDC indicate that only about 40% of health care workers get a flu shot. Dr. Hoven said that often physicians delay getting a shot because they're too busy or want to save the dose for their patients. But she said it's a failing that needs to be corrected.

“In the past, I think health care workers failed to see a connection between themselves and patients they served,” Dr. Hoven said. “So now we say this is something you really need to do for your patients-not for yourself, but for your patients.”

In the future, hospitals might have an incentive to make sure workers are vaccinated. The Joint Commission on Accreditation of Healthcare Organizations has proposed requiring accredited organizations to at least offer immunization to staff, volunteers, and others who have close patient contact. JCAHO is weighing whether to make such an infection control standard mandatory.

WASHINGTON — This winter's flu season is still months away, but officials from the federal government and the American Medical Association say they will be strongly urging physicians to extend influenza vaccine administration beyond its traditional October-December timeframe.

The goal is to protect more Americans and to ensure a more even supply throughout the season.

The effort comes at a time when the vaccine supply is expected to be the largest in U.S. history, with at least 100 million doses slated to be available.

Centers for Disease Control and Prevention and AMA officials discussed their plans at a press briefing sponsored by the National Foundation for Infectious Diseases.

The two organizations began formulating strategies for encouraging a longer vaccination season at the National Influenza Vaccine Summit in January. They and other stakeholders were slated to meet again in late June. With several more high-risk groups targeted for vaccination this year—the CDC has defined 12 target groups—it is getting more difficult for physicians to determine how much vaccine to order and how to effectively manage supply, said Nicole M. Smith, Ph.D., of the CDC's Influenza Division.

There are other barriers to convincing physicians to preorder more vaccine: Any unused supply is essentially “money down the drain,” said Dr. Ardis D. Hoven, medical director of the Bluegrass Care Clinic at the University of Kentucky, Lexington, and a member of the AMA's Board of Trustees. The CDC recommendations encompass about 180 million Americans, said Dr. Hoven.

In most years, vaccination peaks in early October, when about 70% of the vaccine supply has been released, according to CDC data. The demand drops off steeply, usually completely, by late December, which means that most years as much as 30% of the supply goes unused.

Dr. William Schaffner, chairman of the preventive medicine department at Vanderbilt University, Nashville, Tenn., and an NFID board member said that both physicians and patients have fallen into the habit of thinking that if they haven't gotten a shot by late November, they don't need to bother. But he and other officials noted that flu usually peaks in February or March. “We need to persuade them it's not too late to get vaccinated,” Dr. Schaffner said at the briefing.

Physicians have to do some public relations work on their own to make patients aware of this, Dr. Hoven agreed.

And physicians have to be persistent with distributors, she added in an interview. They have “to be more proactive in constantly saying 'When am I getting my doses?,'” she said.

That might not be an easy job. The Health Industry Distributors Association estimates that there are 600 companies that distribute vaccine from two of the three major manufacturers. GlaxoSmithKline, which will have a projected 47 million doses this fall, sells directly only. An estimated 50 million doses will be produced by Sanofi Pasteur. MedImmune Inc. is slated to produce 3 million doses of its live, attenuated nasal vaccine, FluMist. Another 15–20 million doses might become available if the Food and Drug Administration approves a new vaccine from ID Biomedical, which GlaxoSmithKline also owns.

Moreover, the CDC is looking into ways to track the supply so that it can easily locate available doses for physicians, said Dr. Hoven.

Dr. Schaffner said the ramping up of the supply “bodes very well for our attempt to provide protection,” and seems to reflect manufacturers' belief that the market is going to grow.

Physicians and other health care providers are still lagging when it comes to leading by example. Several recent surveys conducted by the AMA and the CDC indicate that only about 40% of health care workers get a flu shot. Dr. Hoven said that often physicians delay getting a shot because they're too busy or want to save the dose for their patients. But she said it's a failing that needs to be corrected.

“In the past, I think health care workers failed to see a connection between themselves and patients they served,” Dr. Hoven said. “So now we say this is something you really need to do for your patients-not for yourself, but for your patients.”

In the future, hospitals might have an incentive to make sure workers are vaccinated. The Joint Commission on Accreditation of Healthcare Organizations has proposed requiring accredited organizations to at least offer immunization to staff, volunteers, and others who have close patient contact. JCAHO is weighing whether to make such an infection control standard mandatory.

The Food and Drug Administration has determined that the antibiotic telithromycin (Ketek) may be associated with serious liver injury and liver failure, and has been linked to four deaths and one liver transplant. The drug's maker, Sanofi-Aventis, has upgraded a caution in the drug's label on the potential for liver injury to a bolded warning that serious hepatic injury has been “observed during or immediately after treatment.” Injury has progressed rapidly after just a few doses, according to the company.

Ketek has not received a black box warning, and both the FDA and Sanofi say the drug's benefits outweigh its risks.

“We are advising both patients taking Ketek and their doctors to be on the alert for signs and symptoms of liver problems,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

However, the drug maker has stopped enrollment in five pediatric trials investigating use of Ketek in acute otitis media, community-acquired pneumonia, and tonsillitis in children 6 months to 18 years old.

The new warning is based partly on an FDA analysis that found that Ketek may be associated with 12 cases of liver failure and 4 deaths since its approval in 2004. “We're engaged in ongoing discussions with the FDA regarding a detailed medical evaluation of hepatic events reported in connection with Ketek use,” said Sanofi spokeswoman Melissa Feltmann.

Ketek is currently approved for use in adults to treat community-acquired pneumonia, sinusitis, and acute exacerbation of chronic bronchitis.

Emmy Tsui, also a Sanofi spokeswoman, said therapy will continue according to protocol in children already enrolled in the five pediatric trials, but that Sanofi would not enroll any new trial participants until it was certain that its development program “remains consistent with the current thinking of the FDA regarding the structure and design of antibiotic drug development in pediatrics.”

The Senate Finance Committee has been investigating Ketek's approval, as well as a postmarketing safety study that was later found to be fraudulent.

Committee chairman CharlesGrassley (R-Iowa) said that he has been stonewalled by the FDA in his attempts to meet with the agency's special agent who investigated the fraud. In mid-June, he visited the Department of Health and Human Services headquarters to demand such a meeting.

“Based on the runaround that's gone on, I smell a cover-up,” Sen. Grassley said in a statement issued after his HHS foray.

The Food and Drug Administration has determined that the antibiotic telithromycin (Ketek) may be associated with serious liver injury and liver failure, and has been linked to four deaths and one liver transplant. The drug's maker, Sanofi-Aventis, has upgraded a caution in the drug's label on the potential for liver injury to a bolded warning that serious hepatic injury has been “observed during or immediately after treatment.” Injury has progressed rapidly after just a few doses, according to the company.

Ketek has not received a black box warning, and both the FDA and Sanofi say the drug's benefits outweigh its risks.

“We are advising both patients taking Ketek and their doctors to be on the alert for signs and symptoms of liver problems,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

However, the drug maker has stopped enrollment in five pediatric trials investigating use of Ketek in acute otitis media, community-acquired pneumonia, and tonsillitis in children 6 months to 18 years old.

The new warning is based partly on an FDA analysis that found that Ketek may be associated with 12 cases of liver failure and 4 deaths since its approval in 2004. “We're engaged in ongoing discussions with the FDA regarding a detailed medical evaluation of hepatic events reported in connection with Ketek use,” said Sanofi spokeswoman Melissa Feltmann.

Ketek is currently approved for use in adults to treat community-acquired pneumonia, sinusitis, and acute exacerbation of chronic bronchitis.

Emmy Tsui, also a Sanofi spokeswoman, said therapy will continue according to protocol in children already enrolled in the five pediatric trials, but that Sanofi would not enroll any new trial participants until it was certain that its development program “remains consistent with the current thinking of the FDA regarding the structure and design of antibiotic drug development in pediatrics.”

The Senate Finance Committee has been investigating Ketek's approval, as well as a postmarketing safety study that was later found to be fraudulent.

Committee chairman CharlesGrassley (R-Iowa) said that he has been stonewalled by the FDA in his attempts to meet with the agency's special agent who investigated the fraud. In mid-June, he visited the Department of Health and Human Services headquarters to demand such a meeting.

“Based on the runaround that's gone on, I smell a cover-up,” Sen. Grassley said in a statement issued after his HHS foray.

The Food and Drug Administration has determined that the antibiotic telithromycin (Ketek) may be associated with serious liver injury and liver failure, and has been linked to four deaths and one liver transplant. The drug's maker, Sanofi-Aventis, has upgraded a caution in the drug's label on the potential for liver injury to a bolded warning that serious hepatic injury has been “observed during or immediately after treatment.” Injury has progressed rapidly after just a few doses, according to the company.

Ketek has not received a black box warning, and both the FDA and Sanofi say the drug's benefits outweigh its risks.

“We are advising both patients taking Ketek and their doctors to be on the alert for signs and symptoms of liver problems,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

However, the drug maker has stopped enrollment in five pediatric trials investigating use of Ketek in acute otitis media, community-acquired pneumonia, and tonsillitis in children 6 months to 18 years old.

The new warning is based partly on an FDA analysis that found that Ketek may be associated with 12 cases of liver failure and 4 deaths since its approval in 2004. “We're engaged in ongoing discussions with the FDA regarding a detailed medical evaluation of hepatic events reported in connection with Ketek use,” said Sanofi spokeswoman Melissa Feltmann.

Ketek is currently approved for use in adults to treat community-acquired pneumonia, sinusitis, and acute exacerbation of chronic bronchitis.

Emmy Tsui, also a Sanofi spokeswoman, said therapy will continue according to protocol in children already enrolled in the five pediatric trials, but that Sanofi would not enroll any new trial participants until it was certain that its development program “remains consistent with the current thinking of the FDA regarding the structure and design of antibiotic drug development in pediatrics.”

The Senate Finance Committee has been investigating Ketek's approval, as well as a postmarketing safety study that was later found to be fraudulent.

Committee chairman CharlesGrassley (R-Iowa) said that he has been stonewalled by the FDA in his attempts to meet with the agency's special agent who investigated the fraud. In mid-June, he visited the Department of Health and Human Services headquarters to demand such a meeting.

“Based on the runaround that's gone on, I smell a cover-up,” Sen. Grassley said in a statement issued after his HHS foray.