Alicia Ault

ASP Decreases Volume for Some

The switch in 2005 to an average sales price (ASP)-based payment method for drugs administered in physician offices under Medicare Part B resulted in substantial price savings for the federal program, according to a report from the Medicare Payment Advisory Commission (MedPAC). The ASP-based system led to an increase in claims volume and total charges; even so, some specialists provided fewer drugs in their offices in 2005, according to MedPAC. Overall, drug spending for Part B fell from $10.9 billion in 2004 to $10.1 billion in 2005. The commission scrutinized how the switch to ASP affected certain specialists. Urologists cut back the most, giving 16% fewer drugs, leading to a 52% decrease in Medicare spending, mostly for hormones that were prescribed for prostate cancer. Rheumatologists increased the drug volume—mostly for infliximab—by 9%; Medicare's spending on that drug was constant, however, according to the report. Infectious disease specialists gave 21% fewer drugs in 2005, possibly because physicians shifted their patients to hospital outpatient and post-acute care settings, the report said. The change may present some patient access and safety issues, according to MedPAC. But there was no reduction in quality of care in other specialties as a result of the switch to ASP.

Monitoring Drug Acquisition

A new law requires the Centers for Medicare and Medicaid Services to keep a closer eye on the Medicare Part B Competitive Acquisition Program. As part of last year's omnibus tax and health care bill (H.R. 6111), Congress established a postpayment review process for CAP, a program under which physicians are paid for administering certain Part B drugs and biologics but do not take on the financial risk of purchasing the drugs. For 2007, only one vendor, BioScrip, has been chosen to participate in CAP. The review program mandated by Congress will be aimed at ensuring that when Medicare pays for a drug or biologic, it has actually been administered to the beneficiary.

Unique New Drugs on Decline

The Food and Drug Administration approved only 18 new molecular entities last year, which is on par with the previous year but close to a historic low. Throughout the 1980s and 1990s, the agency approved at least 20–30 NMEs annually. Among the 18 were four biologic therapies and four new vaccines. The paltry number of approvals and a Government Accountability Office report issued in December may point to a decline in new drug development, according to Representative Henry Waxman (D-Calif.), and Senators Richard Durbin (D-Ill.) and Edward Kennedy (D-Mass.). The legislators requested the GAO report, which found that huge increases in drug industry research and development from 1993 to 2004 were not accompanied by a similar rise in new drug applications—especially for NMEs—to the FDA. From 1993 to 2004, research and development spending increased 147% while NME applications increased by only 7%. NME applications have declined especially since 1995. "These submission trends indicate that the productivity of research and development investments has declined," the GAO report said. In support of that conclusion: Over the same period, the FDA has continued to approve most submissions, but the number approved overall has declined, the GAO said.

FDA Panels Held Less Often

An advocacy group is charging that the FDA is holding outside advisory panel meetings less often than it did a decade ago. Public Citizen's Health Research Group analyzed the 275 advisory committee meetings held from 1997 to 2006. In 1998 and 1999, almost half of approved new molecular entities were preceded by panel meetings; from 2000 to 2006, only 24% (35) of the 147 NMEs approved had a committee meeting first, according to Public Citizen, which put its conclusions in a letter published in the Dec. 23 issue of the Lancet. The group also found that the FDA did not present its scientific opinion as a counterbalance to the drug maker's presentation at 18%, or 49, of the 275 meetings. The FDA overruled the panel conclusions 28% of the time, "a figure higher than is generally assumed," according to Public Citizen.

Easing Use of Experimental Drugs

The FDA is proposing to widen access to experimental drugs. The agency has been accused by patient advocates and some drug makers of obfuscating the criteria that physicians need to seek to use investigational drugs in their patients. In 2003, an Arlington, Va.-based advocacy group, the Abigail Alliance, sued the FDA to get unfettered access to unapproved therapies. The plaintiffs were backed by a federal appeals court in May 2006, and a rehearing of the case is expected to begin in March. In the meantime, the FDA's proposed rule, which was published on Dec. 14, said that the agency was going to make it easier for physicians to access experimental therapies and for manufacturers to make them available. "FDA hopes this proposal will increase awareness in the health care community of the range of options available for obtaining experimental drugs for seriously ill patients," Dr. Janet Woodcock, FDA deputy commissioner for operations, said in a statement. A separate proposed rule would make it easier for manufacturers to recover costs. In a statement, the Abigail Alliance said that the FDA proposals "merely clarify their existing policies."

ASP Decreases Volume for Some

The switch in 2005 to an average sales price (ASP)-based payment method for drugs administered in physician offices under Medicare Part B resulted in substantial price savings for the federal program, according to a report from the Medicare Payment Advisory Commission (MedPAC). The ASP-based system led to an increase in claims volume and total charges; even so, some specialists provided fewer drugs in their offices in 2005, according to MedPAC. Overall, drug spending for Part B fell from $10.9 billion in 2004 to $10.1 billion in 2005. The commission scrutinized how the switch to ASP affected certain specialists. Urologists cut back the most, giving 16% fewer drugs, leading to a 52% decrease in Medicare spending, mostly for hormones that were prescribed for prostate cancer. Rheumatologists increased the drug volume—mostly for infliximab—by 9%; Medicare's spending on that drug was constant, however, according to the report. Infectious disease specialists gave 21% fewer drugs in 2005, possibly because physicians shifted their patients to hospital outpatient and post-acute care settings, the report said. The change may present some patient access and safety issues, according to MedPAC. But there was no reduction in quality of care in other specialties as a result of the switch to ASP.

Monitoring Drug Acquisition

A new law requires the Centers for Medicare and Medicaid Services to keep a closer eye on the Medicare Part B Competitive Acquisition Program. As part of last year's omnibus tax and health care bill (H.R. 6111), Congress established a postpayment review process for CAP, a program under which physicians are paid for administering certain Part B drugs and biologics but do not take on the financial risk of purchasing the drugs. For 2007, only one vendor, BioScrip, has been chosen to participate in CAP. The review program mandated by Congress will be aimed at ensuring that when Medicare pays for a drug or biologic, it has actually been administered to the beneficiary.

Unique New Drugs on Decline

The Food and Drug Administration approved only 18 new molecular entities last year, which is on par with the previous year but close to a historic low. Throughout the 1980s and 1990s, the agency approved at least 20–30 NMEs annually. Among the 18 were four biologic therapies and four new vaccines. The paltry number of approvals and a Government Accountability Office report issued in December may point to a decline in new drug development, according to Representative Henry Waxman (D-Calif.), and Senators Richard Durbin (D-Ill.) and Edward Kennedy (D-Mass.). The legislators requested the GAO report, which found that huge increases in drug industry research and development from 1993 to 2004 were not accompanied by a similar rise in new drug applications—especially for NMEs—to the FDA. From 1993 to 2004, research and development spending increased 147% while NME applications increased by only 7%. NME applications have declined especially since 1995. "These submission trends indicate that the productivity of research and development investments has declined," the GAO report said. In support of that conclusion: Over the same period, the FDA has continued to approve most submissions, but the number approved overall has declined, the GAO said.

FDA Panels Held Less Often

An advocacy group is charging that the FDA is holding outside advisory panel meetings less often than it did a decade ago. Public Citizen's Health Research Group analyzed the 275 advisory committee meetings held from 1997 to 2006. In 1998 and 1999, almost half of approved new molecular entities were preceded by panel meetings; from 2000 to 2006, only 24% (35) of the 147 NMEs approved had a committee meeting first, according to Public Citizen, which put its conclusions in a letter published in the Dec. 23 issue of the Lancet. The group also found that the FDA did not present its scientific opinion as a counterbalance to the drug maker's presentation at 18%, or 49, of the 275 meetings. The FDA overruled the panel conclusions 28% of the time, "a figure higher than is generally assumed," according to Public Citizen.

Easing Use of Experimental Drugs

The FDA is proposing to widen access to experimental drugs. The agency has been accused by patient advocates and some drug makers of obfuscating the criteria that physicians need to seek to use investigational drugs in their patients. In 2003, an Arlington, Va.-based advocacy group, the Abigail Alliance, sued the FDA to get unfettered access to unapproved therapies. The plaintiffs were backed by a federal appeals court in May 2006, and a rehearing of the case is expected to begin in March. In the meantime, the FDA's proposed rule, which was published on Dec. 14, said that the agency was going to make it easier for physicians to access experimental therapies and for manufacturers to make them available. "FDA hopes this proposal will increase awareness in the health care community of the range of options available for obtaining experimental drugs for seriously ill patients," Dr. Janet Woodcock, FDA deputy commissioner for operations, said in a statement. A separate proposed rule would make it easier for manufacturers to recover costs. In a statement, the Abigail Alliance said that the FDA proposals "merely clarify their existing policies."

ASP Decreases Volume for Some

The switch in 2005 to an average sales price (ASP)-based payment method for drugs administered in physician offices under Medicare Part B resulted in substantial price savings for the federal program, according to a report from the Medicare Payment Advisory Commission (MedPAC). The ASP-based system led to an increase in claims volume and total charges; even so, some specialists provided fewer drugs in their offices in 2005, according to MedPAC. Overall, drug spending for Part B fell from $10.9 billion in 2004 to $10.1 billion in 2005. The commission scrutinized how the switch to ASP affected certain specialists. Urologists cut back the most, giving 16% fewer drugs, leading to a 52% decrease in Medicare spending, mostly for hormones that were prescribed for prostate cancer. Rheumatologists increased the drug volume—mostly for infliximab—by 9%; Medicare's spending on that drug was constant, however, according to the report. Infectious disease specialists gave 21% fewer drugs in 2005, possibly because physicians shifted their patients to hospital outpatient and post-acute care settings, the report said. The change may present some patient access and safety issues, according to MedPAC. But there was no reduction in quality of care in other specialties as a result of the switch to ASP.

Monitoring Drug Acquisition

A new law requires the Centers for Medicare and Medicaid Services to keep a closer eye on the Medicare Part B Competitive Acquisition Program. As part of last year's omnibus tax and health care bill (H.R. 6111), Congress established a postpayment review process for CAP, a program under which physicians are paid for administering certain Part B drugs and biologics but do not take on the financial risk of purchasing the drugs. For 2007, only one vendor, BioScrip, has been chosen to participate in CAP. The review program mandated by Congress will be aimed at ensuring that when Medicare pays for a drug or biologic, it has actually been administered to the beneficiary.

Unique New Drugs on Decline

The Food and Drug Administration approved only 18 new molecular entities last year, which is on par with the previous year but close to a historic low. Throughout the 1980s and 1990s, the agency approved at least 20–30 NMEs annually. Among the 18 were four biologic therapies and four new vaccines. The paltry number of approvals and a Government Accountability Office report issued in December may point to a decline in new drug development, according to Representative Henry Waxman (D-Calif.), and Senators Richard Durbin (D-Ill.) and Edward Kennedy (D-Mass.). The legislators requested the GAO report, which found that huge increases in drug industry research and development from 1993 to 2004 were not accompanied by a similar rise in new drug applications—especially for NMEs—to the FDA. From 1993 to 2004, research and development spending increased 147% while NME applications increased by only 7%. NME applications have declined especially since 1995. "These submission trends indicate that the productivity of research and development investments has declined," the GAO report said. In support of that conclusion: Over the same period, the FDA has continued to approve most submissions, but the number approved overall has declined, the GAO said.

FDA Panels Held Less Often

An advocacy group is charging that the FDA is holding outside advisory panel meetings less often than it did a decade ago. Public Citizen's Health Research Group analyzed the 275 advisory committee meetings held from 1997 to 2006. In 1998 and 1999, almost half of approved new molecular entities were preceded by panel meetings; from 2000 to 2006, only 24% (35) of the 147 NMEs approved had a committee meeting first, according to Public Citizen, which put its conclusions in a letter published in the Dec. 23 issue of the Lancet. The group also found that the FDA did not present its scientific opinion as a counterbalance to the drug maker's presentation at 18%, or 49, of the 275 meetings. The FDA overruled the panel conclusions 28% of the time, "a figure higher than is generally assumed," according to Public Citizen.

Easing Use of Experimental Drugs

The FDA is proposing to widen access to experimental drugs. The agency has been accused by patient advocates and some drug makers of obfuscating the criteria that physicians need to seek to use investigational drugs in their patients. In 2003, an Arlington, Va.-based advocacy group, the Abigail Alliance, sued the FDA to get unfettered access to unapproved therapies. The plaintiffs were backed by a federal appeals court in May 2006, and a rehearing of the case is expected to begin in March. In the meantime, the FDA's proposed rule, which was published on Dec. 14, said that the agency was going to make it easier for physicians to access experimental therapies and for manufacturers to make them available. "FDA hopes this proposal will increase awareness in the health care community of the range of options available for obtaining experimental drugs for seriously ill patients," Dr. Janet Woodcock, FDA deputy commissioner for operations, said in a statement. A separate proposed rule would make it easier for manufacturers to recover costs. In a statement, the Abigail Alliance said that the FDA proposals "merely clarify their existing policies."

TORONTO—Available data suggest that light-emitting diode devices are of questionable utility for skin rejuvenation, Dr. Ranella Hirsch said at the annual fall meeting of the American Academy of Facial Plastic and Reconstructive Surgery.

Light-emitting diode (LED) photomodulation devices use nonablative technology—low-intensity light therapy—to nonthermally modulate the activity of living cells, said Dr. Hirsch, who is in private practice in Cambridge, Mass. The devices are used primarily to treat wrinkles, hyperpigmentation, redness, roughness, and pore size, she said.

The most prevalent unit, which has been approved by the Food and Drug Administration, is the GentleWaves LED photomodulation device from Light BioScience.

There is histologic evidence that LED devices stimulate collagen growth and do so without harming the skin's surface, but most of that data have been generated by Light BioScience or investigators with close ties to that manufacturer or other LED makers, Dr. Hirsch said.

The company also submitted data to the FDA that showed some potential clinical benefit after eight patient visits, she said.

LEDs offer an advantage over higher-powered lasers in that they can treat larger areas with lower energy.

It's not certain, however, that there is no benefit at all. Some studies have indicated that LED technology may be useful for wound healing. A literature review published in 2005 found some studies showing improvements in surgical wound healing with low-level laser therapy, but those studies involved a rodent model and would need to be duplicated in pigs and then humans, the authors said (Dermatol. Surg. 2005;31:334–40).

The technology appears to be safe, said Dr. Hirsch, but is "by no definition a home run. I would put it in the same basket as microdermabrasion—by and large, there is no huge benefit, but there is no harm."

Dr. Hirsch expressed other doubts about the technology, including the fact that a physician is not required to administer the therapy. Patients generally sit in front of the units for 10–15 minutes, once a week, for 8–10 weeks.

Dr. Hirsch is a clinical investigator for Candela Corp., Palomar, Cynosure, and Hoya ConBio.

TORONTO—Available data suggest that light-emitting diode devices are of questionable utility for skin rejuvenation, Dr. Ranella Hirsch said at the annual fall meeting of the American Academy of Facial Plastic and Reconstructive Surgery.

Light-emitting diode (LED) photomodulation devices use nonablative technology—low-intensity light therapy—to nonthermally modulate the activity of living cells, said Dr. Hirsch, who is in private practice in Cambridge, Mass. The devices are used primarily to treat wrinkles, hyperpigmentation, redness, roughness, and pore size, she said.

The most prevalent unit, which has been approved by the Food and Drug Administration, is the GentleWaves LED photomodulation device from Light BioScience.

There is histologic evidence that LED devices stimulate collagen growth and do so without harming the skin's surface, but most of that data have been generated by Light BioScience or investigators with close ties to that manufacturer or other LED makers, Dr. Hirsch said.

The company also submitted data to the FDA that showed some potential clinical benefit after eight patient visits, she said.

LEDs offer an advantage over higher-powered lasers in that they can treat larger areas with lower energy.

It's not certain, however, that there is no benefit at all. Some studies have indicated that LED technology may be useful for wound healing. A literature review published in 2005 found some studies showing improvements in surgical wound healing with low-level laser therapy, but those studies involved a rodent model and would need to be duplicated in pigs and then humans, the authors said (Dermatol. Surg. 2005;31:334–40).

The technology appears to be safe, said Dr. Hirsch, but is "by no definition a home run. I would put it in the same basket as microdermabrasion—by and large, there is no huge benefit, but there is no harm."

Dr. Hirsch expressed other doubts about the technology, including the fact that a physician is not required to administer the therapy. Patients generally sit in front of the units for 10–15 minutes, once a week, for 8–10 weeks.

Dr. Hirsch is a clinical investigator for Candela Corp., Palomar, Cynosure, and Hoya ConBio.

TORONTO—Available data suggest that light-emitting diode devices are of questionable utility for skin rejuvenation, Dr. Ranella Hirsch said at the annual fall meeting of the American Academy of Facial Plastic and Reconstructive Surgery.

Light-emitting diode (LED) photomodulation devices use nonablative technology—low-intensity light therapy—to nonthermally modulate the activity of living cells, said Dr. Hirsch, who is in private practice in Cambridge, Mass. The devices are used primarily to treat wrinkles, hyperpigmentation, redness, roughness, and pore size, she said.

The most prevalent unit, which has been approved by the Food and Drug Administration, is the GentleWaves LED photomodulation device from Light BioScience.

There is histologic evidence that LED devices stimulate collagen growth and do so without harming the skin's surface, but most of that data have been generated by Light BioScience or investigators with close ties to that manufacturer or other LED makers, Dr. Hirsch said.

The company also submitted data to the FDA that showed some potential clinical benefit after eight patient visits, she said.

LEDs offer an advantage over higher-powered lasers in that they can treat larger areas with lower energy.

It's not certain, however, that there is no benefit at all. Some studies have indicated that LED technology may be useful for wound healing. A literature review published in 2005 found some studies showing improvements in surgical wound healing with low-level laser therapy, but those studies involved a rodent model and would need to be duplicated in pigs and then humans, the authors said (Dermatol. Surg. 2005;31:334–40).

The technology appears to be safe, said Dr. Hirsch, but is "by no definition a home run. I would put it in the same basket as microdermabrasion—by and large, there is no huge benefit, but there is no harm."

Dr. Hirsch expressed other doubts about the technology, including the fact that a physician is not required to administer the therapy. Patients generally sit in front of the units for 10–15 minutes, once a week, for 8–10 weeks.

Dr. Hirsch is a clinical investigator for Candela Corp., Palomar, Cynosure, and Hoya ConBio.

WASHINGTON — Patients who read at or below the 6th-grade level had a low level of comprehension of instructions on the labels of five commonly used medications, according to a study led by Terry Davis, Ph.D., of the Louisiana State University.

Even though labels seem short and to the point, “many patients need more specific, concrete information,” including instructions on exactly what time of day to take a medication, Dr. Davis said in presenting the findings at a conference on health literacy sponsored by the American College of Physicians.

Along with colleagues at Northwestern University, the University of North Carolina, Western Michigan Area Health Education Center, and Emory University, she queried 395 patients at three clinics that primarily serve the indigent about their understanding of labels for the following drugs: amoxicillin for pediatric use, trimethoprim, guaifenesin, felodipine, and furosemide (Ann. Intern. Med. 2006;145:887–94).

The goal was to determine whether primary care patients could read and correctly state how to take medicines after reading the labels on actual pill bottles, Dr. Davis said. The researchers hypothesized that patients with low literacy were more likely to misunderstand instructions. They also believed that the increasing number of medications taken by Americans is leading to growing confusion and medication errors.

Participants spoke English as a primary language and were not hearing or vision impaired. Half were African American and half were white. The mean age was 45 years, and 29% had a less than high school education. Literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM) test. Of the 395 patients, 19% (75) were deemed to have low literacy, reading at or below a 6th-grade level, and 29% (114) had marginal literacy, reading at the 7th− to 8th-grade level.

All patients were asked how they would take the medicine. A “correct” answer was given if they included all aspects of the label instruction, including dosage, timing, and duration. Overall, 47% (185) of patients misunderstood at least one of the instructions. For marginal-literacy patients, 51% (201) misunderstood one or more instructions, and for low-literacy patients, 63% (249) misunderstood.

The majority—91%, or 359 patients—understood the felodipine instructions, which were, “Take one tablet by mouth once each day.” The lowest level of comprehension was for trimethoprim, which had a label instructing to “take one tablet by mouth twice daily for seven days.”

Higher-literacy patients routinely understood instructions better than those with lower literacy, Dr. Davis said. The adjusted odds ratio of misunderstanding for low literacy was 2.32, and for marginal literacy, 1.94. Most misunderstandings had to do with dosage. For instance, patients commonly believed they should give children a tablespoon instead of a teaspoon of amoxicillin.

Patients who took more medications were also more likely to misunderstand labels, with the adjusted relative risk rising from 2.29 for 1–2 medications to 2.98 for 5 or more medications.

In a substudy, patients were tested on their understanding of the instruction, “Take two tablets by mouth twice daily,” on a bottle of guaifenesin. Overall, 84% were able to correctly state the instruction, but fewer patients knew how many pills to take. Among those with adequate literacy, 80% counted out the correct number of pills. That ability decreased with declining literacy: 63% of marginal literacy patients and 35% of those with low literacy could correctly count the pills.

Dr. Davis and her colleagues said that although this may have reflected patients' numeracy skills more than reading skills, numeracy is an aspect of literacy.

Limitations of the study included the fact that the authors only examined understanding of the primary label. They did not assess patients' actual compliance or drug-taking behavior, whether medication errors occurred, or if any of the patients had experience with any of the five medications.

In an editorial accompanying Dr. Davis' study (Ann. Intern. Med. 2006;145:926–8), Dr. Dean Schillinger wrote that the authors did not fully prove out their conclusion that low literacy is correlated with poor comprehension because they did not “account for patients' cognitive function or visual acuity—each of which can impair reading comprehension and could explain poor understanding of labels.”

But, Dr. Schillinger added, that “does not weaken the conclusion that many patients do not comprehend prescription labels and cannot act on their instructions.”

The study found that 63% of low-literacy patients misunderstood at least one drug-label instruction.

WASHINGTON — Patients who read at or below the 6th-grade level had a low level of comprehension of instructions on the labels of five commonly used medications, according to a study led by Terry Davis, Ph.D., of the Louisiana State University.

Even though labels seem short and to the point, “many patients need more specific, concrete information,” including instructions on exactly what time of day to take a medication, Dr. Davis said in presenting the findings at a conference on health literacy sponsored by the American College of Physicians.

Along with colleagues at Northwestern University, the University of North Carolina, Western Michigan Area Health Education Center, and Emory University, she queried 395 patients at three clinics that primarily serve the indigent about their understanding of labels for the following drugs: amoxicillin for pediatric use, trimethoprim, guaifenesin, felodipine, and furosemide (Ann. Intern. Med. 2006;145:887–94).

The goal was to determine whether primary care patients could read and correctly state how to take medicines after reading the labels on actual pill bottles, Dr. Davis said. The researchers hypothesized that patients with low literacy were more likely to misunderstand instructions. They also believed that the increasing number of medications taken by Americans is leading to growing confusion and medication errors.

Participants spoke English as a primary language and were not hearing or vision impaired. Half were African American and half were white. The mean age was 45 years, and 29% had a less than high school education. Literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM) test. Of the 395 patients, 19% (75) were deemed to have low literacy, reading at or below a 6th-grade level, and 29% (114) had marginal literacy, reading at the 7th− to 8th-grade level.

All patients were asked how they would take the medicine. A “correct” answer was given if they included all aspects of the label instruction, including dosage, timing, and duration. Overall, 47% (185) of patients misunderstood at least one of the instructions. For marginal-literacy patients, 51% (201) misunderstood one or more instructions, and for low-literacy patients, 63% (249) misunderstood.

The majority—91%, or 359 patients—understood the felodipine instructions, which were, “Take one tablet by mouth once each day.” The lowest level of comprehension was for trimethoprim, which had a label instructing to “take one tablet by mouth twice daily for seven days.”

Higher-literacy patients routinely understood instructions better than those with lower literacy, Dr. Davis said. The adjusted odds ratio of misunderstanding for low literacy was 2.32, and for marginal literacy, 1.94. Most misunderstandings had to do with dosage. For instance, patients commonly believed they should give children a tablespoon instead of a teaspoon of amoxicillin.

Patients who took more medications were also more likely to misunderstand labels, with the adjusted relative risk rising from 2.29 for 1–2 medications to 2.98 for 5 or more medications.

In a substudy, patients were tested on their understanding of the instruction, “Take two tablets by mouth twice daily,” on a bottle of guaifenesin. Overall, 84% were able to correctly state the instruction, but fewer patients knew how many pills to take. Among those with adequate literacy, 80% counted out the correct number of pills. That ability decreased with declining literacy: 63% of marginal literacy patients and 35% of those with low literacy could correctly count the pills.

Dr. Davis and her colleagues said that although this may have reflected patients' numeracy skills more than reading skills, numeracy is an aspect of literacy.

Limitations of the study included the fact that the authors only examined understanding of the primary label. They did not assess patients' actual compliance or drug-taking behavior, whether medication errors occurred, or if any of the patients had experience with any of the five medications.

In an editorial accompanying Dr. Davis' study (Ann. Intern. Med. 2006;145:926–8), Dr. Dean Schillinger wrote that the authors did not fully prove out their conclusion that low literacy is correlated with poor comprehension because they did not “account for patients' cognitive function or visual acuity—each of which can impair reading comprehension and could explain poor understanding of labels.”

But, Dr. Schillinger added, that “does not weaken the conclusion that many patients do not comprehend prescription labels and cannot act on their instructions.”

The study found that 63% of low-literacy patients misunderstood at least one drug-label instruction.

WASHINGTON — Patients who read at or below the 6th-grade level had a low level of comprehension of instructions on the labels of five commonly used medications, according to a study led by Terry Davis, Ph.D., of the Louisiana State University.

Even though labels seem short and to the point, “many patients need more specific, concrete information,” including instructions on exactly what time of day to take a medication, Dr. Davis said in presenting the findings at a conference on health literacy sponsored by the American College of Physicians.

Along with colleagues at Northwestern University, the University of North Carolina, Western Michigan Area Health Education Center, and Emory University, she queried 395 patients at three clinics that primarily serve the indigent about their understanding of labels for the following drugs: amoxicillin for pediatric use, trimethoprim, guaifenesin, felodipine, and furosemide (Ann. Intern. Med. 2006;145:887–94).

The goal was to determine whether primary care patients could read and correctly state how to take medicines after reading the labels on actual pill bottles, Dr. Davis said. The researchers hypothesized that patients with low literacy were more likely to misunderstand instructions. They also believed that the increasing number of medications taken by Americans is leading to growing confusion and medication errors.

Participants spoke English as a primary language and were not hearing or vision impaired. Half were African American and half were white. The mean age was 45 years, and 29% had a less than high school education. Literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine (REALM) test. Of the 395 patients, 19% (75) were deemed to have low literacy, reading at or below a 6th-grade level, and 29% (114) had marginal literacy, reading at the 7th− to 8th-grade level.

All patients were asked how they would take the medicine. A “correct” answer was given if they included all aspects of the label instruction, including dosage, timing, and duration. Overall, 47% (185) of patients misunderstood at least one of the instructions. For marginal-literacy patients, 51% (201) misunderstood one or more instructions, and for low-literacy patients, 63% (249) misunderstood.

The majority—91%, or 359 patients—understood the felodipine instructions, which were, “Take one tablet by mouth once each day.” The lowest level of comprehension was for trimethoprim, which had a label instructing to “take one tablet by mouth twice daily for seven days.”

Higher-literacy patients routinely understood instructions better than those with lower literacy, Dr. Davis said. The adjusted odds ratio of misunderstanding for low literacy was 2.32, and for marginal literacy, 1.94. Most misunderstandings had to do with dosage. For instance, patients commonly believed they should give children a tablespoon instead of a teaspoon of amoxicillin.

Patients who took more medications were also more likely to misunderstand labels, with the adjusted relative risk rising from 2.29 for 1–2 medications to 2.98 for 5 or more medications.

In a substudy, patients were tested on their understanding of the instruction, “Take two tablets by mouth twice daily,” on a bottle of guaifenesin. Overall, 84% were able to correctly state the instruction, but fewer patients knew how many pills to take. Among those with adequate literacy, 80% counted out the correct number of pills. That ability decreased with declining literacy: 63% of marginal literacy patients and 35% of those with low literacy could correctly count the pills.

Dr. Davis and her colleagues said that although this may have reflected patients' numeracy skills more than reading skills, numeracy is an aspect of literacy.

Limitations of the study included the fact that the authors only examined understanding of the primary label. They did not assess patients' actual compliance or drug-taking behavior, whether medication errors occurred, or if any of the patients had experience with any of the five medications.

In an editorial accompanying Dr. Davis' study (Ann. Intern. Med. 2006;145:926–8), Dr. Dean Schillinger wrote that the authors did not fully prove out their conclusion that low literacy is correlated with poor comprehension because they did not “account for patients' cognitive function or visual acuity—each of which can impair reading comprehension and could explain poor understanding of labels.”

But, Dr. Schillinger added, that “does not weaken the conclusion that many patients do not comprehend prescription labels and cannot act on their instructions.”

The study found that 63% of low-literacy patients misunderstood at least one drug-label instruction.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services in early November.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007. Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, said the agency. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

Beginning Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

CMS said it is changing how it pays for care in part-time emergency departments. In an effort to track the relative costs of services provided in this type of facility as opposed to a full-fledged ED, CMS created five new HCPCS codes. Medicare will pay for five levels of service in the ED and in clinics and two levels of critical care—one with trauma, one without. The agency said it was backing off for the time being on creating 12 new HCPCS codes for clinics, full-fledged EDs, and critical care.

Finally, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data. To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems.

Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure. “In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services in early November.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007. Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, said the agency. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

Beginning Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

CMS said it is changing how it pays for care in part-time emergency departments. In an effort to track the relative costs of services provided in this type of facility as opposed to a full-fledged ED, CMS created five new HCPCS codes. Medicare will pay for five levels of service in the ED and in clinics and two levels of critical care—one with trauma, one without. The agency said it was backing off for the time being on creating 12 new HCPCS codes for clinics, full-fledged EDs, and critical care.

Finally, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data. To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems.

Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure. “In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services in early November.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007. Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, said the agency. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

Beginning Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

CMS said it is changing how it pays for care in part-time emergency departments. In an effort to track the relative costs of services provided in this type of facility as opposed to a full-fledged ED, CMS created five new HCPCS codes. Medicare will pay for five levels of service in the ED and in clinics and two levels of critical care—one with trauma, one without. The agency said it was backing off for the time being on creating 12 new HCPCS codes for clinics, full-fledged EDs, and critical care.

Finally, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data. To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems.

Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure. “In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

Stopgap funding passed at the end of the last Congress may not be enough to keep the State Children's Health Insurance Program afloat until its expected reauthorization this year, experts said in interviews with this newspaper.

The program, commonly called SCHIP, was established in 1997 and funded with a 10-year, $40 billion allotment beginning in fiscal 1998. But that money has dwindled in recent years as states enrolled more and more children, according to the advocacy group, Families USA.

Under the law, money can be redirected from one state's surplus to plug another's deficit. In December, the 109th Congress voted to redistribute about $219 million in funds to Alaska, Georgia, Illinois, Maryland, Massachusetts, Minnesota, Nebraska, New Jersey, and Rhode Island, according to an analysis by the Washington-based Center for Budget and Policy Priorities.

Those states were expected to face shortfalls first, but eight others—Iowa, Louisiana, Maine, Mississippi, Missouri, North Carolina, South Dakota, and Wisconsin—also are looking at a deficit.

Since they did not get the stopgap help, these states now face even bigger funding gaps than had been projected, according to the CBPP analysis. Those eight states may just be the tip of the iceberg.

“Congress is estimating that 14 states are projected to have insufficient federal SCHIP funds in fiscal year 2007,” Dr. Jay E. Berkelhamer, president of the American Academy of Pediatrics, said in a statement. “This latest action is a down payment on the problem, and gives Congress time to consider more comprehensive solutions in the reauthorization process.”

The stopgap funding will likely buoy the program only until May, at which point “some states may begin to run out of funds and may be forced to reduce enrollment, curtail benefits, increase patient fees, or reduce provider payments,” he said.

The AAP, the March of Dimes, and the National Association of Children's Hospitals are urging Congress to increase SCHIP funding for the program to cover more children, to strengthen Medicaid, and to eliminate barriers that may keep eligible children from enrolling as part of this year's SCHIP reauthorization.

“According to the Current Population Survey, 49% of all uninsured children are eligible for Medicaid and 19% are eligible for SCHIP,” Dr. Jennifer L. Howse, president of the March of Dimes, said in a statement. “States must be given the tools and resources needed to enroll all eligible children in both programs.”

And the groups said they will push to ensure that quality of care gets attention in the next incarnation of SCHIP. “There's been little federal investment in quality and performance measures for children's health care,” Lawrence A. McAndrews, president and CEO of the National Association of Children's Hospitals, said in a statement.

Most advocates believe that Congress will reauthorize the program.

By most measures, SCHIP has been a success. From 1997 to 2005, the number of uninsured children dropped from 22% to 15%, according to a report by the Georgetown University Health Policy Institute's Center for Children and Families. The gain for children came mostly through public coverage such as SCHIP and Medicaid.

Some House and Senate members have said they want to see more eligible children enrolled before they massively expand SCHIP. At least one senator, John Kerry (D-Mass.), plans to reintroduce his legislation, S.114, which was introduced in 2005 and called for coverage of all children. That bill never made it out of the Finance Committee, but may receive more attention under a Democratic Senate.

Stopgap funding passed at the end of the last Congress may not be enough to keep the State Children's Health Insurance Program afloat until its expected reauthorization this year, experts said in interviews with this newspaper.

The program, commonly called SCHIP, was established in 1997 and funded with a 10-year, $40 billion allotment beginning in fiscal 1998. But that money has dwindled in recent years as states enrolled more and more children, according to the advocacy group, Families USA.

Under the law, money can be redirected from one state's surplus to plug another's deficit. In December, the 109th Congress voted to redistribute about $219 million in funds to Alaska, Georgia, Illinois, Maryland, Massachusetts, Minnesota, Nebraska, New Jersey, and Rhode Island, according to an analysis by the Washington-based Center for Budget and Policy Priorities.

Those states were expected to face shortfalls first, but eight others—Iowa, Louisiana, Maine, Mississippi, Missouri, North Carolina, South Dakota, and Wisconsin—also are looking at a deficit.

Since they did not get the stopgap help, these states now face even bigger funding gaps than had been projected, according to the CBPP analysis. Those eight states may just be the tip of the iceberg.

“Congress is estimating that 14 states are projected to have insufficient federal SCHIP funds in fiscal year 2007,” Dr. Jay E. Berkelhamer, president of the American Academy of Pediatrics, said in a statement. “This latest action is a down payment on the problem, and gives Congress time to consider more comprehensive solutions in the reauthorization process.”

The stopgap funding will likely buoy the program only until May, at which point “some states may begin to run out of funds and may be forced to reduce enrollment, curtail benefits, increase patient fees, or reduce provider payments,” he said.

The AAP, the March of Dimes, and the National Association of Children's Hospitals are urging Congress to increase SCHIP funding for the program to cover more children, to strengthen Medicaid, and to eliminate barriers that may keep eligible children from enrolling as part of this year's SCHIP reauthorization.

“According to the Current Population Survey, 49% of all uninsured children are eligible for Medicaid and 19% are eligible for SCHIP,” Dr. Jennifer L. Howse, president of the March of Dimes, said in a statement. “States must be given the tools and resources needed to enroll all eligible children in both programs.”

And the groups said they will push to ensure that quality of care gets attention in the next incarnation of SCHIP. “There's been little federal investment in quality and performance measures for children's health care,” Lawrence A. McAndrews, president and CEO of the National Association of Children's Hospitals, said in a statement.

Most advocates believe that Congress will reauthorize the program.

By most measures, SCHIP has been a success. From 1997 to 2005, the number of uninsured children dropped from 22% to 15%, according to a report by the Georgetown University Health Policy Institute's Center for Children and Families. The gain for children came mostly through public coverage such as SCHIP and Medicaid.

Some House and Senate members have said they want to see more eligible children enrolled before they massively expand SCHIP. At least one senator, John Kerry (D-Mass.), plans to reintroduce his legislation, S.114, which was introduced in 2005 and called for coverage of all children. That bill never made it out of the Finance Committee, but may receive more attention under a Democratic Senate.

Stopgap funding passed at the end of the last Congress may not be enough to keep the State Children's Health Insurance Program afloat until its expected reauthorization this year, experts said in interviews with this newspaper.

The program, commonly called SCHIP, was established in 1997 and funded with a 10-year, $40 billion allotment beginning in fiscal 1998. But that money has dwindled in recent years as states enrolled more and more children, according to the advocacy group, Families USA.

Under the law, money can be redirected from one state's surplus to plug another's deficit. In December, the 109th Congress voted to redistribute about $219 million in funds to Alaska, Georgia, Illinois, Maryland, Massachusetts, Minnesota, Nebraska, New Jersey, and Rhode Island, according to an analysis by the Washington-based Center for Budget and Policy Priorities.

Those states were expected to face shortfalls first, but eight others—Iowa, Louisiana, Maine, Mississippi, Missouri, North Carolina, South Dakota, and Wisconsin—also are looking at a deficit.

Since they did not get the stopgap help, these states now face even bigger funding gaps than had been projected, according to the CBPP analysis. Those eight states may just be the tip of the iceberg.

“Congress is estimating that 14 states are projected to have insufficient federal SCHIP funds in fiscal year 2007,” Dr. Jay E. Berkelhamer, president of the American Academy of Pediatrics, said in a statement. “This latest action is a down payment on the problem, and gives Congress time to consider more comprehensive solutions in the reauthorization process.”

The stopgap funding will likely buoy the program only until May, at which point “some states may begin to run out of funds and may be forced to reduce enrollment, curtail benefits, increase patient fees, or reduce provider payments,” he said.

The AAP, the March of Dimes, and the National Association of Children's Hospitals are urging Congress to increase SCHIP funding for the program to cover more children, to strengthen Medicaid, and to eliminate barriers that may keep eligible children from enrolling as part of this year's SCHIP reauthorization.

“According to the Current Population Survey, 49% of all uninsured children are eligible for Medicaid and 19% are eligible for SCHIP,” Dr. Jennifer L. Howse, president of the March of Dimes, said in a statement. “States must be given the tools and resources needed to enroll all eligible children in both programs.”

And the groups said they will push to ensure that quality of care gets attention in the next incarnation of SCHIP. “There's been little federal investment in quality and performance measures for children's health care,” Lawrence A. McAndrews, president and CEO of the National Association of Children's Hospitals, said in a statement.

Most advocates believe that Congress will reauthorize the program.

By most measures, SCHIP has been a success. From 1997 to 2005, the number of uninsured children dropped from 22% to 15%, according to a report by the Georgetown University Health Policy Institute's Center for Children and Families. The gain for children came mostly through public coverage such as SCHIP and Medicaid.

Some House and Senate members have said they want to see more eligible children enrolled before they massively expand SCHIP. At least one senator, John Kerry (D-Mass.), plans to reintroduce his legislation, S.114, which was introduced in 2005 and called for coverage of all children. That bill never made it out of the Finance Committee, but may receive more attention under a Democratic Senate.

The Food and Drug Administration granted expanded approval to the drug Herceptin. The biologic therapy was approved for use as an adjuvant in combination with doxorubicin, cyclophosphamide, and paclitaxel for treatment of early HER-2 node-positive breast cancer.

Herceptin (trastuzumab), manufactured by Genentech Inc., was first approved by the FDA in 1998 for metastatic breast cancer. The latest approval is based on results from two phase III studies led by the National Surgical Adjuvant Breast and Bowel Project and the North Central Cancer Treatment Group, in collaboration with several National Cancer Institute cooperative groups.

In those studies, 87% of women treated with Herceptin plus the other chemotherapeutics were disease free after 3.5 years, compared with 71% of those treated with the combination minus Herceptin (N. Engl. J. Med. 2005;353:1673–84).

“For women with early-stage HER-2-positive breast cancer, the addition of Herceptin to chemotherapy reduces the relative risk of breast cancer recurrence by approximately half,” Dr. Edward Romond, a professor of medicine in hematology/oncology at the University of Kentucky, Lexington, said in a statement provided by Genentech.

About 212,000 women in the United States will be diagnosed with breast cancer this year. Of those, 25% percent will have HER-2-positive disease.

The approval “is especially good news for women who have breast cancer caused by excessive amounts of HER-2 protein because this cancer typically has a poor prognosis,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

Genentech markets Herceptin in the United States. Roche has licensed Herceptin outside of the United States.

The Food and Drug Administration granted expanded approval to the drug Herceptin. The biologic therapy was approved for use as an adjuvant in combination with doxorubicin, cyclophosphamide, and paclitaxel for treatment of early HER-2 node-positive breast cancer.

Herceptin (trastuzumab), manufactured by Genentech Inc., was first approved by the FDA in 1998 for metastatic breast cancer. The latest approval is based on results from two phase III studies led by the National Surgical Adjuvant Breast and Bowel Project and the North Central Cancer Treatment Group, in collaboration with several National Cancer Institute cooperative groups.

In those studies, 87% of women treated with Herceptin plus the other chemotherapeutics were disease free after 3.5 years, compared with 71% of those treated with the combination minus Herceptin (N. Engl. J. Med. 2005;353:1673–84).

“For women with early-stage HER-2-positive breast cancer, the addition of Herceptin to chemotherapy reduces the relative risk of breast cancer recurrence by approximately half,” Dr. Edward Romond, a professor of medicine in hematology/oncology at the University of Kentucky, Lexington, said in a statement provided by Genentech.

About 212,000 women in the United States will be diagnosed with breast cancer this year. Of those, 25% percent will have HER-2-positive disease.

The approval “is especially good news for women who have breast cancer caused by excessive amounts of HER-2 protein because this cancer typically has a poor prognosis,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

Genentech markets Herceptin in the United States. Roche has licensed Herceptin outside of the United States.

The Food and Drug Administration granted expanded approval to the drug Herceptin. The biologic therapy was approved for use as an adjuvant in combination with doxorubicin, cyclophosphamide, and paclitaxel for treatment of early HER-2 node-positive breast cancer.

Herceptin (trastuzumab), manufactured by Genentech Inc., was first approved by the FDA in 1998 for metastatic breast cancer. The latest approval is based on results from two phase III studies led by the National Surgical Adjuvant Breast and Bowel Project and the North Central Cancer Treatment Group, in collaboration with several National Cancer Institute cooperative groups.

In those studies, 87% of women treated with Herceptin plus the other chemotherapeutics were disease free after 3.5 years, compared with 71% of those treated with the combination minus Herceptin (N. Engl. J. Med. 2005;353:1673–84).

“For women with early-stage HER-2-positive breast cancer, the addition of Herceptin to chemotherapy reduces the relative risk of breast cancer recurrence by approximately half,” Dr. Edward Romond, a professor of medicine in hematology/oncology at the University of Kentucky, Lexington, said in a statement provided by Genentech.

About 212,000 women in the United States will be diagnosed with breast cancer this year. Of those, 25% percent will have HER-2-positive disease.

The approval “is especially good news for women who have breast cancer caused by excessive amounts of HER-2 protein because this cancer typically has a poor prognosis,” Dr. Steven Galson, director of the FDA's Center for Drug Evaluation and Research, said in a statement.

Genentech markets Herceptin in the United States. Roche has licensed Herceptin outside of the United States.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007.

Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, the agency said. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

As of Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

In another change, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data.

To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems. Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure.

“In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007.

Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, the agency said. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

As of Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

In another change, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data.

To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems. Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure.

“In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

Hospitals will get an average 3% increase in pay for outpatient services under a final rule issued by the Centers for Medicare and Medicaid Services.

But CMS also will cut reimbursement for implantation of some devices—mostly neurologic stimulation systems—under the Hospital Outpatient Prospective Payment System rule for 2007.

Not much has changed since the agency first proposed the rule in August, so there are few surprises.

With the 3% increase, Medicare will pay at least $32 billion to hospitals for outpatient procedures in 2007.

CMS has expressed concern that outpatient costs are rising precipitously—an estimated 12% in 2005 and 9% in 2007—mostly because of growth in volume and intensity of services. The increase in costs affects not only Medicare's overall budget but also seniors' pocketbooks due to the 25% copayments for outpatient services, according to the agency.

However, the agency only decreased payments in a few areas, for instance, cutting reimbursement by 3%–9% in 2007 for implantation of some neurologic devices. The agency said it will reduce payments for implantation of a neurostimulator—used to treat Parkinson's disease and essential tremor—by 7%, to $11,500 for 2007. CMS is reducing coverage of implantation of the leads and electrodes attached to the device by 9%, from $14,900 to $13,500.

Implantable cardiology devices such as pacemakers and implantable cardioverter defibrillators also are slated for increases. However, Medicare will no longer cover the cost of a device that is replaced under warranty or as part of a recall, the agency said. In the past, Medicare has paid for the procedure and the device, even though the hospital usually receives it free of charge.

As of Jan. 1, the hospital can only charge less than $1.01 for those devices. The minimal charge will ensure that the claim is accepted and will also help CMS identify and track recalls, according to the agency.

In a statement, device industry group AdvaMed mostly supported the new rule, but continued to object to the agency using 2-year-old claims data as a basis for the new payment rates.

Some procedures will be getting a fairly big boost, including implantation of drug infusion reservoirs (60% increase), drug infusion devices (16% increase), and pain management catheters (11% increase).

In another change, hospitals will not have to begin reporting on outpatient quality in 2007. CMS lifted that requirement, which was proposed in the initial rule and would have required reporting on certain measures to receive the increase in overall payments. Instead, the agency has postponed that requirement until 2009. In the meantime, CMS will develop outpatient-specific quality measures.

The American Hospital Association applauded the delay. “The AHA is pleased that CMS will develop quality measures specifically for the outpatient setting and has correctly given hospitals ample time to implement a reporting system for hospital outpatient services,” AHA Executive Vice President Rick Pollack said in a statement.

As incongruous as it seems, as part of the final rule on outpatient pay, hospitals also will be required to submit more inpatient quality data.

To get the full inpatient pay increase in 2008, hospitals will have to report on measures endorsed by the National Quality Forum, and also measure patient satisfaction using the Hospital Consumer Assessment of Healthcare Providers and Systems. Hospitals also will have to report risk-adjusted inpatient outcome measures such as 30-day mortality for patients hospitalized with acute myocardial infarction or heart failure.

“In this final rule, we are taking one more step toward rewarding hospitals for providing quality care, not just in the inpatient setting but also in the outpatient department,” Leslie Norwalk, CMS acting administrator, said in a statement.

The Food and Drug Administration has announced that it is taking steps to improve its postmarketing surveillance of medical device safety, including moving ahead on a proposal to require electronic reporting of adverse events.

The agency said it has created an action plan based on a major review that was completed in 2005. That review looked at how the Center for Radiological Devices and Health (CDRH) handles recalls and enforcement actions against manufacturers that are not in compliance with FDA rules.

The report “details a number of action items that we believe will transform the postmarketing safety program,” Dr. Daniel Schultz, director of CDRH, said in a briefing with reporters.

The FDA will focus on improvements in four major areas: collaboration among experts within CDRH, data systems, communications with patients and physicians about risks and benefits, and enforcement.

CDRH leaders will encourage more cross-organizational collaboration so premarket, postmarket, and enforcement efforts are better coordinated, he said.

Some of the biggest changes will come in data collection and analysis. The agency hopes to integrate its passive adverse events reporting system (Manufacturer and User Facility Device Experience Database, also known as MAUDE) and its active system, the Medical Product Safety Device Network (MedSun), Dr. Schultz said. Currently, 350 hospitals have been trained to report device problems on MedSun. One goal is to recruit more facilities and upgrade reporting so it is closer to real-time.

The agency also hopes to require manufacturers and others to electronically report adverse events. Currently, FDA receives about 200,000 reports to MAUDE each year, and most are on paper, which delays entry into the system and analysis for safety signals, Dr. Schultz said. The FDA has been piloting an electronic reporting program, and is writing a rule to require electronic reporting, he said.

Once data are being reported and analyzed more quickly, enforcement will be more timely also. This will let the FDA focus enforcement efforts on the highest-risk products, Dr. Schultz said.

The Food and Drug Administration has announced that it is taking steps to improve its postmarketing surveillance of medical device safety, including moving ahead on a proposal to require electronic reporting of adverse events.

The agency said it has created an action plan based on a major review that was completed in 2005. That review looked at how the Center for Radiological Devices and Health (CDRH) handles recalls and enforcement actions against manufacturers that are not in compliance with FDA rules.

The report “details a number of action items that we believe will transform the postmarketing safety program,” Dr. Daniel Schultz, director of CDRH, said in a briefing with reporters.

The FDA will focus on improvements in four major areas: collaboration among experts within CDRH, data systems, communications with patients and physicians about risks and benefits, and enforcement.

CDRH leaders will encourage more cross-organizational collaboration so premarket, postmarket, and enforcement efforts are better coordinated, he said.

Some of the biggest changes will come in data collection and analysis. The agency hopes to integrate its passive adverse events reporting system (Manufacturer and User Facility Device Experience Database, also known as MAUDE) and its active system, the Medical Product Safety Device Network (MedSun), Dr. Schultz said. Currently, 350 hospitals have been trained to report device problems on MedSun. One goal is to recruit more facilities and upgrade reporting so it is closer to real-time.

The agency also hopes to require manufacturers and others to electronically report adverse events. Currently, FDA receives about 200,000 reports to MAUDE each year, and most are on paper, which delays entry into the system and analysis for safety signals, Dr. Schultz said. The FDA has been piloting an electronic reporting program, and is writing a rule to require electronic reporting, he said.

Once data are being reported and analyzed more quickly, enforcement will be more timely also. This will let the FDA focus enforcement efforts on the highest-risk products, Dr. Schultz said.

The Food and Drug Administration has announced that it is taking steps to improve its postmarketing surveillance of medical device safety, including moving ahead on a proposal to require electronic reporting of adverse events.

The agency said it has created an action plan based on a major review that was completed in 2005. That review looked at how the Center for Radiological Devices and Health (CDRH) handles recalls and enforcement actions against manufacturers that are not in compliance with FDA rules.

The report “details a number of action items that we believe will transform the postmarketing safety program,” Dr. Daniel Schultz, director of CDRH, said in a briefing with reporters.

The FDA will focus on improvements in four major areas: collaboration among experts within CDRH, data systems, communications with patients and physicians about risks and benefits, and enforcement.

CDRH leaders will encourage more cross-organizational collaboration so premarket, postmarket, and enforcement efforts are better coordinated, he said.

Some of the biggest changes will come in data collection and analysis. The agency hopes to integrate its passive adverse events reporting system (Manufacturer and User Facility Device Experience Database, also known as MAUDE) and its active system, the Medical Product Safety Device Network (MedSun), Dr. Schultz said. Currently, 350 hospitals have been trained to report device problems on MedSun. One goal is to recruit more facilities and upgrade reporting so it is closer to real-time.

The agency also hopes to require manufacturers and others to electronically report adverse events. Currently, FDA receives about 200,000 reports to MAUDE each year, and most are on paper, which delays entry into the system and analysis for safety signals, Dr. Schultz said. The FDA has been piloting an electronic reporting program, and is writing a rule to require electronic reporting, he said.

Once data are being reported and analyzed more quickly, enforcement will be more timely also. This will let the FDA focus enforcement efforts on the highest-risk products, Dr. Schultz said.

SILVER SPRING, MD. — The antibiotic Ketek (telithromycin) is neither safe nor effective for treating acute exacerbation of chronic bronchitis or acute sinusitis, according to a Food and Drug Administration advisory committee that recommended that the agency remove those indications from the drug's approved labeling.

The panel—a joint meeting of the FDA's Anti-Infective Drugs and Drug Safety and Risk Management Advisory committees—concluded that although Ketek has been marketed since 2004, safety concerns argue against using the drug in two conditions that generally resolve on their own.

The panel voted 16–3 that Ketek should retain its approval for treating mild to moderate community-acquired pneumonia, but as a second- or third-line therapy. Ketek's maker, Sanofi-Aventis, also presented data suggesting that the drug may be effective against multidrug resistant Streptococcus pneumoniae, which was persuasive to the committee.

Although the panel supported keeping Ketek on the market, a majority of panelists recommended that a black box warning be added to the labeling.

“This is a drug that we need, but this is not something I'd reach for, and this is something I'd discourage people from using,” said Dr. Margo Smith, a panelist from the Washington Hospital Center.

If the FDA follows the panel's advice, as it normally does, the agency would determine how to educate physicians on the revised uses. Sanofi-Aventis agreed that it would create a medication guide for consumers. The FDA and Sanofi-Aventis would work out the content of the black box warning, which is likely to touch on the potential for liver toxicity, visual disturbances, loss of consciousness, and exacerbations of myasthenia gravis.

Ketek was under scrutiny during most of 2006. Senator Chuck Grassley (R-Iowa) has alleged that the drug was approved on the basis of a fraudulent trial, known as study 3014. On the eve of the 2-day FDA panel meeting, Sen. Grassley released results—so far—of his Finance Committee's Ketek investigation. He alleged that FDA managers failed to notify the Anti-Infective Drugs Advisory Committee when it met in 2003 that the agency had concerns about study 3014's integrity.

The panel recommended approval at that time. The agency later held a closed-door meeting with the panel to discuss problems with study 3014, but Sen. Grassley alleges that the committee members still were not given a complete story.

In making the original approval decision, the agency determined that it could toss out tainted data from study 3014 and instead rely on postmarketing data collected on about 4 million patient exposures in Europe, said Dr. Janice Soreth, director of the FDA's division of anti-infective and ophthalmology products, at the December meeting.

Several speakers at the FDA meeting—including a recently departed reviewer from the Ketek team—expressed outrage over the agency's reliance on postmarketing data instead of a prospective safety study for approval.

The panel did not seem as concerned.

The older postmarketing safety information—combined with updated surveillance reports from Europe and postmarketing data collected in the United States since Ketek's introduction—was presented at length.

FDA staffers disagreed on the incidence and import of side effects, as did the FDA and Sanofi-Aventis. Sanofi estimated that to date, the reporting rate in Europe for serious hepatic reactions is 4–10 cases/million courses of therapy. According to the FDA, from 2004 to 2006 there were 12 cases of acute liver failure among 5 million U.S. prescriptions, for a reporting rate of 23 per 10 million prescriptions. By comparison, the antibiotic Trovan (trovafloxacin) had a rate of 58 per 10 million in its first year on the market. The drug was subsequently recalled.

The FDA asked several experts from the Drug-Induced Liver Injury Network to take a closer look at 53 reports of hepatic toxicity associated with Ketek use. The network is a cooperative funded by the National Institute of Diabetes, Digestive, and Kidney Disorders.

One of those experts, Dr. William Lee, director of the clinical center for liver diseases at the University of Texas at Dallas, said that of the 53 patients, 44 were hospitalized, 5 died, and 2 had liver transplants. The cases had similar clinical features, including rapid onset, prominent fever, joint aches, and right upper quadrant pain.

Dr. Lee said he believed that 28 of the 53 cases were very likely or probably caused by Ketek, 17 were possibly related, and 8 had insufficient data to make a ruling. He said the hospitalization rate was probably 1 in 20,000 or 1 in 30,000 for liver toxicity and 1 in 150,000 for acute liver failure. Ketek's profile would be worse if it was a chronic medication, he said.

“The severity may be limited simply because the drug exposure is quite short,” Dr. Lee said.

Sanofi maintained that the hepatotoxicity was similar to that of other antibiotics. The panel was split on whether Ketek was an outlier.

Committee members were more concerned about exacerbations of myasthenia gravis, a neurologic condition affecting about 35,000–70,000 Americans. Many individuals aren't aware they have the condition and might unwittingly take Ketek. The FDA's review found 33 reports of exacerbations of myasthenia gravis since 2004. Of those, seven were life threatening. Twelve patients required a ventilator or intubation.

There were 71 cases of vision disorders and 23 cases of disturbances in consciousness with serious outcomes. In one case, an 18-year-old passed out while driving and struck and killed a pedestrian.

Sanofi-Aventis stuck to its data showing that Ketek was no different from other drugs in the class. “Overall, we believe that the safety risks with telithromycin appear to be similar to widely prescribed antibiotics,” said Dr. Bruno Leroy, head of the company's internal medicine franchise.

Some FDA staffers were not convinced. “Ketek stands out among the macrolides in its unique and notable toxicity,” said Dr. Rosemary Johann-Liang, deputy director of the division of drug risk evaluation at FDA's Center for Drug Evaluation and Research.

Ketek has been prescribed to 6 million U.S. patients since 2004, according to Sanofi-Aventis.

SILVER SPRING, MD. — The antibiotic Ketek (telithromycin) is neither safe nor effective for treating acute exacerbation of chronic bronchitis or acute sinusitis, according to a Food and Drug Administration advisory committee that recommended that the agency remove those indications from the drug's approved labeling.

The panel—a joint meeting of the FDA's Anti-Infective Drugs and Drug Safety and Risk Management Advisory committees—concluded that although Ketek has been marketed since 2004, safety concerns argue against using the drug in two conditions that generally resolve on their own.

The panel voted 16–3 that Ketek should retain its approval for treating mild to moderate community-acquired pneumonia, but as a second- or third-line therapy. Ketek's maker, Sanofi-Aventis, also presented data suggesting that the drug may be effective against multidrug resistant Streptococcus pneumoniae, which was persuasive to the committee.

Although the panel supported keeping Ketek on the market, a majority of panelists recommended that a black box warning be added to the labeling.

“This is a drug that we need, but this is not something I'd reach for, and this is something I'd discourage people from using,” said Dr. Margo Smith, a panelist from the Washington Hospital Center.

If the FDA follows the panel's advice, as it normally does, the agency would determine how to educate physicians on the revised uses. Sanofi-Aventis agreed that it would create a medication guide for consumers. The FDA and Sanofi-Aventis would work out the content of the black box warning, which is likely to touch on the potential for liver toxicity, visual disturbances, loss of consciousness, and exacerbations of myasthenia gravis.

Ketek was under scrutiny during most of 2006. Senator Chuck Grassley (R-Iowa) has alleged that the drug was approved on the basis of a fraudulent trial, known as study 3014. On the eve of the 2-day FDA panel meeting, Sen. Grassley released results—so far—of his Finance Committee's Ketek investigation. He alleged that FDA managers failed to notify the Anti-Infective Drugs Advisory Committee when it met in 2003 that the agency had concerns about study 3014's integrity.

The panel recommended approval at that time. The agency later held a closed-door meeting with the panel to discuss problems with study 3014, but Sen. Grassley alleges that the committee members still were not given a complete story.

In making the original approval decision, the agency determined that it could toss out tainted data from study 3014 and instead rely on postmarketing data collected on about 4 million patient exposures in Europe, said Dr. Janice Soreth, director of the FDA's division of anti-infective and ophthalmology products, at the December meeting.

Several speakers at the FDA meeting—including a recently departed reviewer from the Ketek team—expressed outrage over the agency's reliance on postmarketing data instead of a prospective safety study for approval.

The panel did not seem as concerned.

The older postmarketing safety information—combined with updated surveillance reports from Europe and postmarketing data collected in the United States since Ketek's introduction—was presented at length.

FDA staffers disagreed on the incidence and import of side effects, as did the FDA and Sanofi-Aventis. Sanofi estimated that to date, the reporting rate in Europe for serious hepatic reactions is 4–10 cases/million courses of therapy. According to the FDA, from 2004 to 2006 there were 12 cases of acute liver failure among 5 million U.S. prescriptions, for a reporting rate of 23 per 10 million prescriptions. By comparison, the antibiotic Trovan (trovafloxacin) had a rate of 58 per 10 million in its first year on the market. The drug was subsequently recalled.

The FDA asked several experts from the Drug-Induced Liver Injury Network to take a closer look at 53 reports of hepatic toxicity associated with Ketek use. The network is a cooperative funded by the National Institute of Diabetes, Digestive, and Kidney Disorders.

One of those experts, Dr. William Lee, director of the clinical center for liver diseases at the University of Texas at Dallas, said that of the 53 patients, 44 were hospitalized, 5 died, and 2 had liver transplants. The cases had similar clinical features, including rapid onset, prominent fever, joint aches, and right upper quadrant pain.

Dr. Lee said he believed that 28 of the 53 cases were very likely or probably caused by Ketek, 17 were possibly related, and 8 had insufficient data to make a ruling. He said the hospitalization rate was probably 1 in 20,000 or 1 in 30,000 for liver toxicity and 1 in 150,000 for acute liver failure. Ketek's profile would be worse if it was a chronic medication, he said.

“The severity may be limited simply because the drug exposure is quite short,” Dr. Lee said.

Sanofi maintained that the hepatotoxicity was similar to that of other antibiotics. The panel was split on whether Ketek was an outlier.

Committee members were more concerned about exacerbations of myasthenia gravis, a neurologic condition affecting about 35,000–70,000 Americans. Many individuals aren't aware they have the condition and might unwittingly take Ketek. The FDA's review found 33 reports of exacerbations of myasthenia gravis since 2004. Of those, seven were life threatening. Twelve patients required a ventilator or intubation.

There were 71 cases of vision disorders and 23 cases of disturbances in consciousness with serious outcomes. In one case, an 18-year-old passed out while driving and struck and killed a pedestrian.

Sanofi-Aventis stuck to its data showing that Ketek was no different from other drugs in the class. “Overall, we believe that the safety risks with telithromycin appear to be similar to widely prescribed antibiotics,” said Dr. Bruno Leroy, head of the company's internal medicine franchise.

Some FDA staffers were not convinced. “Ketek stands out among the macrolides in its unique and notable toxicity,” said Dr. Rosemary Johann-Liang, deputy director of the division of drug risk evaluation at FDA's Center for Drug Evaluation and Research.

Ketek has been prescribed to 6 million U.S. patients since 2004, according to Sanofi-Aventis.

SILVER SPRING, MD. — The antibiotic Ketek (telithromycin) is neither safe nor effective for treating acute exacerbation of chronic bronchitis or acute sinusitis, according to a Food and Drug Administration advisory committee that recommended that the agency remove those indications from the drug's approved labeling.

The panel—a joint meeting of the FDA's Anti-Infective Drugs and Drug Safety and Risk Management Advisory committees—concluded that although Ketek has been marketed since 2004, safety concerns argue against using the drug in two conditions that generally resolve on their own.

The panel voted 16–3 that Ketek should retain its approval for treating mild to moderate community-acquired pneumonia, but as a second- or third-line therapy. Ketek's maker, Sanofi-Aventis, also presented data suggesting that the drug may be effective against multidrug resistant Streptococcus pneumoniae, which was persuasive to the committee.

Although the panel supported keeping Ketek on the market, a majority of panelists recommended that a black box warning be added to the labeling.

“This is a drug that we need, but this is not something I'd reach for, and this is something I'd discourage people from using,” said Dr. Margo Smith, a panelist from the Washington Hospital Center.

If the FDA follows the panel's advice, as it normally does, the agency would determine how to educate physicians on the revised uses. Sanofi-Aventis agreed that it would create a medication guide for consumers. The FDA and Sanofi-Aventis would work out the content of the black box warning, which is likely to touch on the potential for liver toxicity, visual disturbances, loss of consciousness, and exacerbations of myasthenia gravis.

Ketek was under scrutiny during most of 2006. Senator Chuck Grassley (R-Iowa) has alleged that the drug was approved on the basis of a fraudulent trial, known as study 3014. On the eve of the 2-day FDA panel meeting, Sen. Grassley released results—so far—of his Finance Committee's Ketek investigation. He alleged that FDA managers failed to notify the Anti-Infective Drugs Advisory Committee when it met in 2003 that the agency had concerns about study 3014's integrity.

The panel recommended approval at that time. The agency later held a closed-door meeting with the panel to discuss problems with study 3014, but Sen. Grassley alleges that the committee members still were not given a complete story.

In making the original approval decision, the agency determined that it could toss out tainted data from study 3014 and instead rely on postmarketing data collected on about 4 million patient exposures in Europe, said Dr. Janice Soreth, director of the FDA's division of anti-infective and ophthalmology products, at the December meeting.

Several speakers at the FDA meeting—including a recently departed reviewer from the Ketek team—expressed outrage over the agency's reliance on postmarketing data instead of a prospective safety study for approval.

The panel did not seem as concerned.

The older postmarketing safety information—combined with updated surveillance reports from Europe and postmarketing data collected in the United States since Ketek's introduction—was presented at length.

FDA staffers disagreed on the incidence and import of side effects, as did the FDA and Sanofi-Aventis. Sanofi estimated that to date, the reporting rate in Europe for serious hepatic reactions is 4–10 cases/million courses of therapy. According to the FDA, from 2004 to 2006 there were 12 cases of acute liver failure among 5 million U.S. prescriptions, for a reporting rate of 23 per 10 million prescriptions. By comparison, the antibiotic Trovan (trovafloxacin) had a rate of 58 per 10 million in its first year on the market. The drug was subsequently recalled.

The FDA asked several experts from the Drug-Induced Liver Injury Network to take a closer look at 53 reports of hepatic toxicity associated with Ketek use. The network is a cooperative funded by the National Institute of Diabetes, Digestive, and Kidney Disorders.

One of those experts, Dr. William Lee, director of the clinical center for liver diseases at the University of Texas at Dallas, said that of the 53 patients, 44 were hospitalized, 5 died, and 2 had liver transplants. The cases had similar clinical features, including rapid onset, prominent fever, joint aches, and right upper quadrant pain.

Dr. Lee said he believed that 28 of the 53 cases were very likely or probably caused by Ketek, 17 were possibly related, and 8 had insufficient data to make a ruling. He said the hospitalization rate was probably 1 in 20,000 or 1 in 30,000 for liver toxicity and 1 in 150,000 for acute liver failure. Ketek's profile would be worse if it was a chronic medication, he said.

“The severity may be limited simply because the drug exposure is quite short,” Dr. Lee said.

Sanofi maintained that the hepatotoxicity was similar to that of other antibiotics. The panel was split on whether Ketek was an outlier.

Committee members were more concerned about exacerbations of myasthenia gravis, a neurologic condition affecting about 35,000–70,000 Americans. Many individuals aren't aware they have the condition and might unwittingly take Ketek. The FDA's review found 33 reports of exacerbations of myasthenia gravis since 2004. Of those, seven were life threatening. Twelve patients required a ventilator or intubation.

There were 71 cases of vision disorders and 23 cases of disturbances in consciousness with serious outcomes. In one case, an 18-year-old passed out while driving and struck and killed a pedestrian.

Sanofi-Aventis stuck to its data showing that Ketek was no different from other drugs in the class. “Overall, we believe that the safety risks with telithromycin appear to be similar to widely prescribed antibiotics,” said Dr. Bruno Leroy, head of the company's internal medicine franchise.

Some FDA staffers were not convinced. “Ketek stands out among the macrolides in its unique and notable toxicity,” said Dr. Rosemary Johann-Liang, deputy director of the division of drug risk evaluation at FDA's Center for Drug Evaluation and Research.

Ketek has been prescribed to 6 million U.S. patients since 2004, according to Sanofi-Aventis.

The Food and Drug Administration is proposing that all over-the-counter analgesic, antipyretic, and antirheumatic drugs carry new, stronger warnings on the potential for hepatic toxicity and gastrointestinal bleeding.

The warnings will be carried on products used by both adults and children, said Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, in a briefing with reporters.

Currently, manufacturers can choose what language to use and where to place the warnings. The FDA proposal would require standardized language and also dictate where the warnings appear on packaging and in what type size. Dr. Ganley said that the words “liver warning” and “stomach warning” would be in bold type and be listed as the first warning.

All acetaminophen packages will warn that severe liver damage can occur if more than the maximum recommended dosage is taken in 24 hours, if it is taken with other drugs containing acetaminophen, and if the user has more than three alcoholic drinks in a day while using the product, said Dr. Ganley.

There had been an alcohol warning before; now it will be incorporated into the liver warning section, he said.

The word “acetaminophen” will have to be highlighted on the medicine's container and its carton, he said, adding that many consumers aren't aware that a product contains acetaminophen. There will be a similar requirement for the term “NSAID” on aspirin, ibuprofen, naproxen, and ketoprofen containers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) also will carry a bold, large type “stomach warning,” cautioning that the risk of GI bleeding is increased for patients over age 60; who have stomach ulcers or bleeding; who are taking a blood thinner, or steroid medication; or another drug containing an NSAID; who have more than three alcoholic drinks a day; and who take it for longer than directed.

While it has been known for decades that acetaminophen is linked to liver damage, and that NSAIDs can cause GI bleeding, the agency has not been able to move quickly in requiring manufacturers to more prominently display warnings, said Dr. Ganley.

OTC drugs have to be addressed as a class through a formal rule-making process, he said. The agency held advisory committee hearings on OTC painkiller safety issues in 2002. This rule is a result of those recommendations, Dr. Ganley said.

Some critics were not satisfied. “What took the agency so long?” asked Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group, in a statement.

Dr. Lurie said that his organization presented data in 2002 showing that there were 26,000 hospitalizations and 450 deaths a year that were attributable to acetaminophen overdoses. The group has pushed for regulations similar to those in the United Kingdom, which limit the number of pills per package and mg per pill.

As part of this proposed rule, the FDA is seeking comment on whether such limitations should be adopted in the United States, said Dr. Ganley. He added that recent research shows there may be an increase in acute liver failure due to acetaminophen. In the paper he cited, researchers found that the annual percentage of acetaminophen-related acute liver failure increased from 28% in 1998 to 51% in 2003 (Hepatology 2005;42:1364–72).

“It is still a great concern to us that this is occurring, and there is a suggestion that it may be increasing,” said Dr. Ganley.

There has been no such increase in toxicity seen with NSAIDs. But, said Dr. Ganley, “These drugs are used by tens of millions of people every week in the U.S.” Though he said that in general, “they are quite safe,” he added that with so many people taking the medications, rare events will be seen more often.

After taking comment through June 2007, the FDA hopes to write a final rule by the year's end, said Dr. Ganley. He would not predict when manufacturers might have to start complying.

The Consumer Healthcare Products Association (CHPA) said that its member companies welcomed the changes. “The reality is, however, that over-the-counter medicines are real medicines with real risks if misused,” said CHPA president Linda Suydam in a statement.

The Food and Drug Administration is proposing that all over-the-counter analgesic, antipyretic, and antirheumatic drugs carry new, stronger warnings on the potential for hepatic toxicity and gastrointestinal bleeding.

The warnings will be carried on products used by both adults and children, said Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, in a briefing with reporters.

Currently, manufacturers can choose what language to use and where to place the warnings. The FDA proposal would require standardized language and also dictate where the warnings appear on packaging and in what type size. Dr. Ganley said that the words “liver warning” and “stomach warning” would be in bold type and be listed as the first warning.

All acetaminophen packages will warn that severe liver damage can occur if more than the maximum recommended dosage is taken in 24 hours, if it is taken with other drugs containing acetaminophen, and if the user has more than three alcoholic drinks in a day while using the product, said Dr. Ganley.

There had been an alcohol warning before; now it will be incorporated into the liver warning section, he said.

The word “acetaminophen” will have to be highlighted on the medicine's container and its carton, he said, adding that many consumers aren't aware that a product contains acetaminophen. There will be a similar requirement for the term “NSAID” on aspirin, ibuprofen, naproxen, and ketoprofen containers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) also will carry a bold, large type “stomach warning,” cautioning that the risk of GI bleeding is increased for patients over age 60; who have stomach ulcers or bleeding; who are taking a blood thinner, or steroid medication; or another drug containing an NSAID; who have more than three alcoholic drinks a day; and who take it for longer than directed.

While it has been known for decades that acetaminophen is linked to liver damage, and that NSAIDs can cause GI bleeding, the agency has not been able to move quickly in requiring manufacturers to more prominently display warnings, said Dr. Ganley.

OTC drugs have to be addressed as a class through a formal rule-making process, he said. The agency held advisory committee hearings on OTC painkiller safety issues in 2002. This rule is a result of those recommendations, Dr. Ganley said.

Some critics were not satisfied. “What took the agency so long?” asked Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group, in a statement.

Dr. Lurie said that his organization presented data in 2002 showing that there were 26,000 hospitalizations and 450 deaths a year that were attributable to acetaminophen overdoses. The group has pushed for regulations similar to those in the United Kingdom, which limit the number of pills per package and mg per pill.

As part of this proposed rule, the FDA is seeking comment on whether such limitations should be adopted in the United States, said Dr. Ganley. He added that recent research shows there may be an increase in acute liver failure due to acetaminophen. In the paper he cited, researchers found that the annual percentage of acetaminophen-related acute liver failure increased from 28% in 1998 to 51% in 2003 (Hepatology 2005;42:1364–72).

“It is still a great concern to us that this is occurring, and there is a suggestion that it may be increasing,” said Dr. Ganley.

There has been no such increase in toxicity seen with NSAIDs. But, said Dr. Ganley, “These drugs are used by tens of millions of people every week in the U.S.” Though he said that in general, “they are quite safe,” he added that with so many people taking the medications, rare events will be seen more often.

After taking comment through June 2007, the FDA hopes to write a final rule by the year's end, said Dr. Ganley. He would not predict when manufacturers might have to start complying.

The Consumer Healthcare Products Association (CHPA) said that its member companies welcomed the changes. “The reality is, however, that over-the-counter medicines are real medicines with real risks if misused,” said CHPA president Linda Suydam in a statement.

The Food and Drug Administration is proposing that all over-the-counter analgesic, antipyretic, and antirheumatic drugs carry new, stronger warnings on the potential for hepatic toxicity and gastrointestinal bleeding.

The warnings will be carried on products used by both adults and children, said Dr. Charles Ganley, director of the FDA's Office of Nonprescription Products, in a briefing with reporters.

Currently, manufacturers can choose what language to use and where to place the warnings. The FDA proposal would require standardized language and also dictate where the warnings appear on packaging and in what type size. Dr. Ganley said that the words “liver warning” and “stomach warning” would be in bold type and be listed as the first warning.

All acetaminophen packages will warn that severe liver damage can occur if more than the maximum recommended dosage is taken in 24 hours, if it is taken with other drugs containing acetaminophen, and if the user has more than three alcoholic drinks in a day while using the product, said Dr. Ganley.

There had been an alcohol warning before; now it will be incorporated into the liver warning section, he said.

The word “acetaminophen” will have to be highlighted on the medicine's container and its carton, he said, adding that many consumers aren't aware that a product contains acetaminophen. There will be a similar requirement for the term “NSAID” on aspirin, ibuprofen, naproxen, and ketoprofen containers.

Nonsteroidal anti-inflammatory drugs (NSAIDs) also will carry a bold, large type “stomach warning,” cautioning that the risk of GI bleeding is increased for patients over age 60; who have stomach ulcers or bleeding; who are taking a blood thinner, or steroid medication; or another drug containing an NSAID; who have more than three alcoholic drinks a day; and who take it for longer than directed.

While it has been known for decades that acetaminophen is linked to liver damage, and that NSAIDs can cause GI bleeding, the agency has not been able to move quickly in requiring manufacturers to more prominently display warnings, said Dr. Ganley.

OTC drugs have to be addressed as a class through a formal rule-making process, he said. The agency held advisory committee hearings on OTC painkiller safety issues in 2002. This rule is a result of those recommendations, Dr. Ganley said.

Some critics were not satisfied. “What took the agency so long?” asked Dr. Peter Lurie, deputy director of Public Citizen's Health Research Group, in a statement.

Dr. Lurie said that his organization presented data in 2002 showing that there were 26,000 hospitalizations and 450 deaths a year that were attributable to acetaminophen overdoses. The group has pushed for regulations similar to those in the United Kingdom, which limit the number of pills per package and mg per pill.

As part of this proposed rule, the FDA is seeking comment on whether such limitations should be adopted in the United States, said Dr. Ganley. He added that recent research shows there may be an increase in acute liver failure due to acetaminophen. In the paper he cited, researchers found that the annual percentage of acetaminophen-related acute liver failure increased from 28% in 1998 to 51% in 2003 (Hepatology 2005;42:1364–72).

“It is still a great concern to us that this is occurring, and there is a suggestion that it may be increasing,” said Dr. Ganley.

There has been no such increase in toxicity seen with NSAIDs. But, said Dr. Ganley, “These drugs are used by tens of millions of people every week in the U.S.” Though he said that in general, “they are quite safe,” he added that with so many people taking the medications, rare events will be seen more often.

After taking comment through June 2007, the FDA hopes to write a final rule by the year's end, said Dr. Ganley. He would not predict when manufacturers might have to start complying.

The Consumer Healthcare Products Association (CHPA) said that its member companies welcomed the changes. “The reality is, however, that over-the-counter medicines are real medicines with real risks if misused,” said CHPA president Linda Suydam in a statement.