Mark S. Lesney

A 2-plus-1 dosing schedule of the commonly used heptavalent pneumococcal conjugate vaccine showed satisfactory antibody responses to all serotypes of the bacteria, comparable with published immunogenicity studies on the 3-plus-1 dose schedule typically used.

The descriptive, nonrandomized trial was performed on children at 3, 5, and 12 months of age, and 99 of 101 healthy infants completed the study, wrote Helena Käyhty, Ph.D., of the National Public Health Institute, Helsinki, Finland, and her colleagues.

The investigators compared the geometric mean antibody concentrations obtained for all serotypes with published immunogenicity results, including those from two efficacy trials—the Northern California Kaiser-Permanente study and the Finnish Otitis Media Vaccine Trial—that used the standard 3-plus-1 schedule with different end points—invasive disease or acute otitis media.

A similar German trial with a 3-plus-1 schedule was also compared with the present study; it measured a slightly lower incidence of fever, a common symptom that was usually mild.

“At 13 months, 1 month after the third dose of PCV, antibody concentrations measured in this study were as high as those in the previous Finnish, U.S., and German studies and were distributed similarly with respect to those in the previous Finnish study after four doses, indicating equally good immunologic priming after two to three doses in early infancy,” the investigators said (Pediatr. Infect. Dis. J. 2005;24:108-14).

Serious adverse events observed for four children were lethargy/irritability, gastroenteritis, and scarlatina; one of these was considered as possibly related to the vaccinations. “All serious adverse symptoms disappeared within 3-6 days,” the authors wrote.

Due to the results of this study, and because “preliminary postmarketing surveillance reports from the United States suggest that two doses in the primary series are sufficient for protection,” the authors suggested that the use of fewer than four doses may be a practical option for the administration of the PCV.

A 2-plus-1 dosing schedule of the commonly used heptavalent pneumococcal conjugate vaccine showed satisfactory antibody responses to all serotypes of the bacteria, comparable with published immunogenicity studies on the 3-plus-1 dose schedule typically used.

The descriptive, nonrandomized trial was performed on children at 3, 5, and 12 months of age, and 99 of 101 healthy infants completed the study, wrote Helena Käyhty, Ph.D., of the National Public Health Institute, Helsinki, Finland, and her colleagues.

The investigators compared the geometric mean antibody concentrations obtained for all serotypes with published immunogenicity results, including those from two efficacy trials—the Northern California Kaiser-Permanente study and the Finnish Otitis Media Vaccine Trial—that used the standard 3-plus-1 schedule with different end points—invasive disease or acute otitis media.

A similar German trial with a 3-plus-1 schedule was also compared with the present study; it measured a slightly lower incidence of fever, a common symptom that was usually mild.

“At 13 months, 1 month after the third dose of PCV, antibody concentrations measured in this study were as high as those in the previous Finnish, U.S., and German studies and were distributed similarly with respect to those in the previous Finnish study after four doses, indicating equally good immunologic priming after two to three doses in early infancy,” the investigators said (Pediatr. Infect. Dis. J. 2005;24:108-14).

Serious adverse events observed for four children were lethargy/irritability, gastroenteritis, and scarlatina; one of these was considered as possibly related to the vaccinations. “All serious adverse symptoms disappeared within 3-6 days,” the authors wrote.

Due to the results of this study, and because “preliminary postmarketing surveillance reports from the United States suggest that two doses in the primary series are sufficient for protection,” the authors suggested that the use of fewer than four doses may be a practical option for the administration of the PCV.

A 2-plus-1 dosing schedule of the commonly used heptavalent pneumococcal conjugate vaccine showed satisfactory antibody responses to all serotypes of the bacteria, comparable with published immunogenicity studies on the 3-plus-1 dose schedule typically used.

The descriptive, nonrandomized trial was performed on children at 3, 5, and 12 months of age, and 99 of 101 healthy infants completed the study, wrote Helena Käyhty, Ph.D., of the National Public Health Institute, Helsinki, Finland, and her colleagues.

The investigators compared the geometric mean antibody concentrations obtained for all serotypes with published immunogenicity results, including those from two efficacy trials—the Northern California Kaiser-Permanente study and the Finnish Otitis Media Vaccine Trial—that used the standard 3-plus-1 schedule with different end points—invasive disease or acute otitis media.

A similar German trial with a 3-plus-1 schedule was also compared with the present study; it measured a slightly lower incidence of fever, a common symptom that was usually mild.

“At 13 months, 1 month after the third dose of PCV, antibody concentrations measured in this study were as high as those in the previous Finnish, U.S., and German studies and were distributed similarly with respect to those in the previous Finnish study after four doses, indicating equally good immunologic priming after two to three doses in early infancy,” the investigators said (Pediatr. Infect. Dis. J. 2005;24:108-14).

Serious adverse events observed for four children were lethargy/irritability, gastroenteritis, and scarlatina; one of these was considered as possibly related to the vaccinations. “All serious adverse symptoms disappeared within 3-6 days,” the authors wrote.

Due to the results of this study, and because “preliminary postmarketing surveillance reports from the United States suggest that two doses in the primary series are sufficient for protection,” the authors suggested that the use of fewer than four doses may be a practical option for the administration of the PCV.

Evidence of a heightened risk of rhabdomyolysis in Asian Americans led the Food and Drug Administration to issue an alert and to require a label revision for the statin rosuvastatin last month.

According to the FDA Public Health Advisory, in a phase IV pharmacokinetic study “involving a diverse population of Asians residing in the United States, rosuvastatin [Crestor] drug levels were found to be elevated approximately twofold, compared with a Caucasian control group.”

Because the risks of statin side effects have been shown to be dose dependent, a change to the Dosage and Administration section of the label was made to state that the 5-mg dose should be considered the starting dose for Asian patients, and any increase in dose should take into consideration the increased drug exposure in this patient population. The new label also emphasizes that 40 mg should not be used as a starting dose and should only be used in patients “who have not achieved their cholesterol goals with the 20-mg dose.”

All statins are known to create a risk of myopathy/rhabdomyolysis, and the original Crestor product label included a warning that patients of advanced age (older than 65 years) or those who had hypothyroidism and/or renal insufficiency should be considered to be at greater risk of developing myopathy while receiving a statin and should be started at low doses and carefully monitored.

In 2004 the drug's maker, AstraZeneca Pharmaceuticals LP, found itself under attack by Public Citizen Health Research Group, which petitioned the FDA to have rosuvastatin removed from the market because of safety concerns regarding the risk of myopathy/rhabdomyolysis.

In June, the FDA issued a public health advisory alert to physicians emphasizing that physicians should pay close attention to the rosuvastatin label regarding dosage, “to cut the risk of myopathy.”

Just days after the current advisory was released, Public Citizen renewed its call for the drug's withdrawal, citing its own analysis of adverse event reports in which the rate of rhabdomyolysis per million prescriptions filled for rosuvastatin was 6.2 times higher than the rate for all of the other statins combined.

The FDA denied the request, stating, “We do not believe that the adverse event reports on Crestor indicate the drug poses and unacceptable risk of rhabdomyolysis” and that extensive preapproval and ongoing clinical trial-safety experience indicates that rosuvastatin's muscle safety is comparable to that of other statins.

Evidence of a heightened risk of rhabdomyolysis in Asian Americans led the Food and Drug Administration to issue an alert and to require a label revision for the statin rosuvastatin last month.

According to the FDA Public Health Advisory, in a phase IV pharmacokinetic study “involving a diverse population of Asians residing in the United States, rosuvastatin [Crestor] drug levels were found to be elevated approximately twofold, compared with a Caucasian control group.”

Because the risks of statin side effects have been shown to be dose dependent, a change to the Dosage and Administration section of the label was made to state that the 5-mg dose should be considered the starting dose for Asian patients, and any increase in dose should take into consideration the increased drug exposure in this patient population. The new label also emphasizes that 40 mg should not be used as a starting dose and should only be used in patients “who have not achieved their cholesterol goals with the 20-mg dose.”

All statins are known to create a risk of myopathy/rhabdomyolysis, and the original Crestor product label included a warning that patients of advanced age (older than 65 years) or those who had hypothyroidism and/or renal insufficiency should be considered to be at greater risk of developing myopathy while receiving a statin and should be started at low doses and carefully monitored.

In 2004 the drug's maker, AstraZeneca Pharmaceuticals LP, found itself under attack by Public Citizen Health Research Group, which petitioned the FDA to have rosuvastatin removed from the market because of safety concerns regarding the risk of myopathy/rhabdomyolysis.

In June, the FDA issued a public health advisory alert to physicians emphasizing that physicians should pay close attention to the rosuvastatin label regarding dosage, “to cut the risk of myopathy.”

Just days after the current advisory was released, Public Citizen renewed its call for the drug's withdrawal, citing its own analysis of adverse event reports in which the rate of rhabdomyolysis per million prescriptions filled for rosuvastatin was 6.2 times higher than the rate for all of the other statins combined.

The FDA denied the request, stating, “We do not believe that the adverse event reports on Crestor indicate the drug poses and unacceptable risk of rhabdomyolysis” and that extensive preapproval and ongoing clinical trial-safety experience indicates that rosuvastatin's muscle safety is comparable to that of other statins.

Evidence of a heightened risk of rhabdomyolysis in Asian Americans led the Food and Drug Administration to issue an alert and to require a label revision for the statin rosuvastatin last month.

According to the FDA Public Health Advisory, in a phase IV pharmacokinetic study “involving a diverse population of Asians residing in the United States, rosuvastatin [Crestor] drug levels were found to be elevated approximately twofold, compared with a Caucasian control group.”

Because the risks of statin side effects have been shown to be dose dependent, a change to the Dosage and Administration section of the label was made to state that the 5-mg dose should be considered the starting dose for Asian patients, and any increase in dose should take into consideration the increased drug exposure in this patient population. The new label also emphasizes that 40 mg should not be used as a starting dose and should only be used in patients “who have not achieved their cholesterol goals with the 20-mg dose.”

All statins are known to create a risk of myopathy/rhabdomyolysis, and the original Crestor product label included a warning that patients of advanced age (older than 65 years) or those who had hypothyroidism and/or renal insufficiency should be considered to be at greater risk of developing myopathy while receiving a statin and should be started at low doses and carefully monitored.

In 2004 the drug's maker, AstraZeneca Pharmaceuticals LP, found itself under attack by Public Citizen Health Research Group, which petitioned the FDA to have rosuvastatin removed from the market because of safety concerns regarding the risk of myopathy/rhabdomyolysis.

In June, the FDA issued a public health advisory alert to physicians emphasizing that physicians should pay close attention to the rosuvastatin label regarding dosage, “to cut the risk of myopathy.”

Just days after the current advisory was released, Public Citizen renewed its call for the drug's withdrawal, citing its own analysis of adverse event reports in which the rate of rhabdomyolysis per million prescriptions filled for rosuvastatin was 6.2 times higher than the rate for all of the other statins combined.

The FDA denied the request, stating, “We do not believe that the adverse event reports on Crestor indicate the drug poses and unacceptable risk of rhabdomyolysis” and that extensive preapproval and ongoing clinical trial-safety experience indicates that rosuvastatin's muscle safety is comparable to that of other statins.

BETHESDA, MD. — A federal advisory panel unanimously recommended that only one of the current virus strains be changed in the production of the 2005–2006 influenza vaccine.

At last month's meeting of the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, the decision was made to retain the influenza A (H1N1) A/New Calendonia/20/99 strain, and the influenza B/Shanghai/361/2002-like strains.

The only change recommended was to replace the influenza A (H3N2) strain with an emerging contender, one of the California-like influenza strains that were first identifed as new by the Centers for Disease Control and Prevention.

Designated A/California/7/2004, because it originated in a patient from Santa Clara County last year, the new strain proved to be one of a family of strains identified as emerging in various locations across the globe. The decision to maintain two strains and to change one in response to the emerging California-like viruses “harmonizes”—in the words of one advisory panel member—the U.S. recommendation with the identical recommendation given mere days before by the World Health Organization as to next year's vaccine mix.

Retaining last year's choices seemed appropriate for the influenza A (H1N1) and influenza B strains because there was no significant change in predominance of the strains seen in the current season, said Roland Levandowski, M.D., of the FDA's division of viral products. But there was a noticeable migration of strains of influenza A (H3N2) with the appearance of the new California strain first identified in January.

The CDC is currently trying to grow four variations of the California-like influenza virus in eggs—the first step in seeing if vaccine can be produced from the virus—with low to moderate results, said Zhiping Ye, M.D., of the FDA. Dr. Ye also noted that six national laboratories in the United States, the United Kingdom, and Japan also are working to develop A/California/7/2004-like candidates in anticipation of demand. These would be made available as candidate viruses for manufacturers to test for their suitability for bulk vaccine production.

Dr. Levandowski noted that no California-like strain had yet reached the manufacturers. But previous experience indicated that there should be no particular problem for the industry to adapt to such a recommendation in time for the next flu season, given those strains under development.

One political issue surfaced during the meeting when a number of the panelists indicated that the nearness in time of the WHO decision might make it appear that the U.S. panel was acting simply as a rubber stamp. But according to Nancy Cox, Ph.D., chief of the CDC's influenza branch, when the FDA panel meeting was held earlier than the WHO meeting, the rest of the world thought that the United States was preempting the global initiative.

Since then, the meeting has been deliberately scheduled as soon as possible after the WHO deliberations in which, according to Dr. Cox, CDC always plays a significant role. This timing, she said, was especially important because the CDC was able to return with and process the most up-to-date global information in time for presentation to the FDA panel.

Panelists and speakers alike reiterated the difficulties that manufacturers face in producing a trivalent vaccine within the short turnaround period dictated by the timing of the committee's recommendation.

A presentation by Albert Thomas, director of viral manufacturing for Sanofi Pasteur, detailed the process used by manufacturers, and emphasized how companies, seeking to accelerate the process, actually started producing the first of the monovalent strains before the committee met. That entailed an “at-risk decision” because of the economic repercussions should they prove wrong in picking which strain was the most likely to be used.

Federal authorities also are concerned about the potential spread of avian influenza. Last September, the Department of Health and Human Services awarded a contract to Aventis Pasteur to manufacture and store 2 million doses of vaccine against avian influenza A (H5N1).

The CDC has developed and distributed a test kit to detect the currently circulating H5N1 strain and is collaborating with the WHO and the National Institutes of Health on the development of additional vaccine strain candidates.

A 'B'-Deviling Problem When Caring for Children

Dealing with the B strains of the influenza virus remains a continuing problem, especially in children, according to the vaccine advisory committee.

Influenza B viruses that are currently circulating can be divided into two distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87 (

www.cdc.gov/flu/weekly

But for the current season, Yamagata-lineage strains were predicted to predominate once more and the vaccine strain recommendation was changed to B/Shanghai/2002-like viruses, a subset of the Yamagata strains.

In adults and even the elderly, choice of which of these strain candidates to include in the final vaccine is less critical, as it has been noted that each provides some measure of immunity to the others.

But this is not the case in children, making proper prediction of which strain will predominate far more critical, especially as B virus outbreaks have been known to cause pediatric deaths.

Advisory panel members who specialize in the care of children, including Philip S. LaRussa, M.D., professor of clinical pediatrics, Columbia University, New York, and Gary D. Overturf, M.D., professor of pediatrics and pathology, University of New Mexico, Albuquerque, questioned if it would be possible for the panel to propose the development of a pediatric vaccine which would combine both types of B viruses in a single formulation. In discussion, the consensus was that such a formulation would need clinical testing, and initiating such testing did not fall under the authority of the panel, nor even of the FDA. Any such new vaccine would have to be initiated by a manufacturer and brought to the FDA through channels.

If necessary, it would be appropriate to recommend a monovalent vaccine with the alternative B strain to be given in addition to the trivalent standard for pediatric patients. It is well known that such vaccines are effective, Dr. Levandowski said.

BETHESDA, MD. — A federal advisory panel unanimously recommended that only one of the current virus strains be changed in the production of the 2005–2006 influenza vaccine.

At last month's meeting of the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, the decision was made to retain the influenza A (H1N1) A/New Calendonia/20/99 strain, and the influenza B/Shanghai/361/2002-like strains.

The only change recommended was to replace the influenza A (H3N2) strain with an emerging contender, one of the California-like influenza strains that were first identifed as new by the Centers for Disease Control and Prevention.

Designated A/California/7/2004, because it originated in a patient from Santa Clara County last year, the new strain proved to be one of a family of strains identified as emerging in various locations across the globe. The decision to maintain two strains and to change one in response to the emerging California-like viruses “harmonizes”—in the words of one advisory panel member—the U.S. recommendation with the identical recommendation given mere days before by the World Health Organization as to next year's vaccine mix.

Retaining last year's choices seemed appropriate for the influenza A (H1N1) and influenza B strains because there was no significant change in predominance of the strains seen in the current season, said Roland Levandowski, M.D., of the FDA's division of viral products. But there was a noticeable migration of strains of influenza A (H3N2) with the appearance of the new California strain first identified in January.

The CDC is currently trying to grow four variations of the California-like influenza virus in eggs—the first step in seeing if vaccine can be produced from the virus—with low to moderate results, said Zhiping Ye, M.D., of the FDA. Dr. Ye also noted that six national laboratories in the United States, the United Kingdom, and Japan also are working to develop A/California/7/2004-like candidates in anticipation of demand. These would be made available as candidate viruses for manufacturers to test for their suitability for bulk vaccine production.

Dr. Levandowski noted that no California-like strain had yet reached the manufacturers. But previous experience indicated that there should be no particular problem for the industry to adapt to such a recommendation in time for the next flu season, given those strains under development.

One political issue surfaced during the meeting when a number of the panelists indicated that the nearness in time of the WHO decision might make it appear that the U.S. panel was acting simply as a rubber stamp. But according to Nancy Cox, Ph.D., chief of the CDC's influenza branch, when the FDA panel meeting was held earlier than the WHO meeting, the rest of the world thought that the United States was preempting the global initiative.

Since then, the meeting has been deliberately scheduled as soon as possible after the WHO deliberations in which, according to Dr. Cox, CDC always plays a significant role. This timing, she said, was especially important because the CDC was able to return with and process the most up-to-date global information in time for presentation to the FDA panel.

Panelists and speakers alike reiterated the difficulties that manufacturers face in producing a trivalent vaccine within the short turnaround period dictated by the timing of the committee's recommendation.

A presentation by Albert Thomas, director of viral manufacturing for Sanofi Pasteur, detailed the process used by manufacturers, and emphasized how companies, seeking to accelerate the process, actually started producing the first of the monovalent strains before the committee met. That entailed an “at-risk decision” because of the economic repercussions should they prove wrong in picking which strain was the most likely to be used.

Federal authorities also are concerned about the potential spread of avian influenza. Last September, the Department of Health and Human Services awarded a contract to Aventis Pasteur to manufacture and store 2 million doses of vaccine against avian influenza A (H5N1).

The CDC has developed and distributed a test kit to detect the currently circulating H5N1 strain and is collaborating with the WHO and the National Institutes of Health on the development of additional vaccine strain candidates.

A 'B'-Deviling Problem When Caring for Children

Dealing with the B strains of the influenza virus remains a continuing problem, especially in children, according to the vaccine advisory committee.

Influenza B viruses that are currently circulating can be divided into two distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87 (

www.cdc.gov/flu/weekly

But for the current season, Yamagata-lineage strains were predicted to predominate once more and the vaccine strain recommendation was changed to B/Shanghai/2002-like viruses, a subset of the Yamagata strains.

In adults and even the elderly, choice of which of these strain candidates to include in the final vaccine is less critical, as it has been noted that each provides some measure of immunity to the others.

But this is not the case in children, making proper prediction of which strain will predominate far more critical, especially as B virus outbreaks have been known to cause pediatric deaths.

Advisory panel members who specialize in the care of children, including Philip S. LaRussa, M.D., professor of clinical pediatrics, Columbia University, New York, and Gary D. Overturf, M.D., professor of pediatrics and pathology, University of New Mexico, Albuquerque, questioned if it would be possible for the panel to propose the development of a pediatric vaccine which would combine both types of B viruses in a single formulation. In discussion, the consensus was that such a formulation would need clinical testing, and initiating such testing did not fall under the authority of the panel, nor even of the FDA. Any such new vaccine would have to be initiated by a manufacturer and brought to the FDA through channels.

If necessary, it would be appropriate to recommend a monovalent vaccine with the alternative B strain to be given in addition to the trivalent standard for pediatric patients. It is well known that such vaccines are effective, Dr. Levandowski said.

BETHESDA, MD. — A federal advisory panel unanimously recommended that only one of the current virus strains be changed in the production of the 2005–2006 influenza vaccine.

At last month's meeting of the Food and Drug Administration's Vaccines and Related Biological Products Advisory Committee, the decision was made to retain the influenza A (H1N1) A/New Calendonia/20/99 strain, and the influenza B/Shanghai/361/2002-like strains.

The only change recommended was to replace the influenza A (H3N2) strain with an emerging contender, one of the California-like influenza strains that were first identifed as new by the Centers for Disease Control and Prevention.

Designated A/California/7/2004, because it originated in a patient from Santa Clara County last year, the new strain proved to be one of a family of strains identified as emerging in various locations across the globe. The decision to maintain two strains and to change one in response to the emerging California-like viruses “harmonizes”—in the words of one advisory panel member—the U.S. recommendation with the identical recommendation given mere days before by the World Health Organization as to next year's vaccine mix.

Retaining last year's choices seemed appropriate for the influenza A (H1N1) and influenza B strains because there was no significant change in predominance of the strains seen in the current season, said Roland Levandowski, M.D., of the FDA's division of viral products. But there was a noticeable migration of strains of influenza A (H3N2) with the appearance of the new California strain first identified in January.

The CDC is currently trying to grow four variations of the California-like influenza virus in eggs—the first step in seeing if vaccine can be produced from the virus—with low to moderate results, said Zhiping Ye, M.D., of the FDA. Dr. Ye also noted that six national laboratories in the United States, the United Kingdom, and Japan also are working to develop A/California/7/2004-like candidates in anticipation of demand. These would be made available as candidate viruses for manufacturers to test for their suitability for bulk vaccine production.

Dr. Levandowski noted that no California-like strain had yet reached the manufacturers. But previous experience indicated that there should be no particular problem for the industry to adapt to such a recommendation in time for the next flu season, given those strains under development.

One political issue surfaced during the meeting when a number of the panelists indicated that the nearness in time of the WHO decision might make it appear that the U.S. panel was acting simply as a rubber stamp. But according to Nancy Cox, Ph.D., chief of the CDC's influenza branch, when the FDA panel meeting was held earlier than the WHO meeting, the rest of the world thought that the United States was preempting the global initiative.

Since then, the meeting has been deliberately scheduled as soon as possible after the WHO deliberations in which, according to Dr. Cox, CDC always plays a significant role. This timing, she said, was especially important because the CDC was able to return with and process the most up-to-date global information in time for presentation to the FDA panel.

Panelists and speakers alike reiterated the difficulties that manufacturers face in producing a trivalent vaccine within the short turnaround period dictated by the timing of the committee's recommendation.

A presentation by Albert Thomas, director of viral manufacturing for Sanofi Pasteur, detailed the process used by manufacturers, and emphasized how companies, seeking to accelerate the process, actually started producing the first of the monovalent strains before the committee met. That entailed an “at-risk decision” because of the economic repercussions should they prove wrong in picking which strain was the most likely to be used.

Federal authorities also are concerned about the potential spread of avian influenza. Last September, the Department of Health and Human Services awarded a contract to Aventis Pasteur to manufacture and store 2 million doses of vaccine against avian influenza A (H5N1).

The CDC has developed and distributed a test kit to detect the currently circulating H5N1 strain and is collaborating with the WHO and the National Institutes of Health on the development of additional vaccine strain candidates.

A 'B'-Deviling Problem When Caring for Children

Dealing with the B strains of the influenza virus remains a continuing problem, especially in children, according to the vaccine advisory committee.

Influenza B viruses that are currently circulating can be divided into two distinct lineages represented by B/Yamagata/16/88 and B/Victoria/2/87 (

www.cdc.gov/flu/weekly

But for the current season, Yamagata-lineage strains were predicted to predominate once more and the vaccine strain recommendation was changed to B/Shanghai/2002-like viruses, a subset of the Yamagata strains.

In adults and even the elderly, choice of which of these strain candidates to include in the final vaccine is less critical, as it has been noted that each provides some measure of immunity to the others.

But this is not the case in children, making proper prediction of which strain will predominate far more critical, especially as B virus outbreaks have been known to cause pediatric deaths.

Advisory panel members who specialize in the care of children, including Philip S. LaRussa, M.D., professor of clinical pediatrics, Columbia University, New York, and Gary D. Overturf, M.D., professor of pediatrics and pathology, University of New Mexico, Albuquerque, questioned if it would be possible for the panel to propose the development of a pediatric vaccine which would combine both types of B viruses in a single formulation. In discussion, the consensus was that such a formulation would need clinical testing, and initiating such testing did not fall under the authority of the panel, nor even of the FDA. Any such new vaccine would have to be initiated by a manufacturer and brought to the FDA through channels.

If necessary, it would be appropriate to recommend a monovalent vaccine with the alternative B strain to be given in addition to the trivalent standard for pediatric patients. It is well known that such vaccines are effective, Dr. Levandowski said.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these are events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Other study reporting sites have been developed by specific pharmaceutical companies. These include the GlaxoSmithKline Clinical Trial Register, which encompasses clinical trials completed since the formation of GSK on December 27, 2000—a move in part due to settlement of the GSK lawsuit involving the antidepressant Paxil (paroxetine). (See box.)

In a statement, GSK “welcomed” the announcement of the joint position paper and declared that the company will continue to post on its own site as well as “post information about GSK-sponsored patient trials initiated on or after Nov. 1, 2004, on clinicaltrials.gov

From Courts to Congress, Several Pharmaceutical Companies Took Heat in 2004

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these are events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Other study reporting sites have been developed by specific pharmaceutical companies. These include the GlaxoSmithKline Clinical Trial Register, which encompasses clinical trials completed since the formation of GSK on December 27, 2000—a move in part due to settlement of the GSK lawsuit involving the antidepressant Paxil (paroxetine). (See box.)

In a statement, GSK “welcomed” the announcement of the joint position paper and declared that the company will continue to post on its own site as well as “post information about GSK-sponsored patient trials initiated on or after Nov. 1, 2004, on clinicaltrials.gov

From Courts to Congress, Several Pharmaceutical Companies Took Heat in 2004

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these are events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Other study reporting sites have been developed by specific pharmaceutical companies. These include the GlaxoSmithKline Clinical Trial Register, which encompasses clinical trials completed since the formation of GSK on December 27, 2000—a move in part due to settlement of the GSK lawsuit involving the antidepressant Paxil (paroxetine). (See box.)

In a statement, GSK “welcomed” the announcement of the joint position paper and declared that the company will continue to post on its own site as well as “post information about GSK-sponsored patient trials initiated on or after Nov. 1, 2004, on clinicaltrials.gov

From Courts to Congress, Several Pharmaceutical Companies Took Heat in 2004

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence.

The Food and Drug Administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in patients with severe pulmonary hypertension. In nature, prostacyclin is a local hormone; intravenous introduction can result in systemic side effects and progressive tolerance, requiring more and more of the drug.

The randomized clinical trial reported for approval was conducted on 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6‐9 inhalations per day) was 19%, compared with 4% for the placebo group. The response rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost is dispensed in single‐use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Labeling indicated that iloprost should not be inhaled more than once every 2 hours, and the drug is not effective while a patient is sleeping. Vital signs should be monitored when initiating iloprost because of the risk of syncope.

Iloprost, though not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, which markets the drug in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA in August 2004.

Clinical trials are underway in the United States to examine its interaction with other drug treatments for PAH, as well as for its potential as a preventive agent for lung cancer in heavy smokers.

The Food and Drug Administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in patients with severe pulmonary hypertension. In nature, prostacyclin is a local hormone; intravenous introduction can result in systemic side effects and progressive tolerance, requiring more and more of the drug.

The randomized clinical trial reported for approval was conducted on 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6‐9 inhalations per day) was 19%, compared with 4% for the placebo group. The response rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost is dispensed in single‐use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Labeling indicated that iloprost should not be inhaled more than once every 2 hours, and the drug is not effective while a patient is sleeping. Vital signs should be monitored when initiating iloprost because of the risk of syncope.

Iloprost, though not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, which markets the drug in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA in August 2004.

Clinical trials are underway in the United States to examine its interaction with other drug treatments for PAH, as well as for its potential as a preventive agent for lung cancer in heavy smokers.

The Food and Drug Administration approved the first inhaled therapy for pulmonary arterial hypertension in December.

Iloprost, a stable synthetic analogue of prostacyclin, causes selective pulmonary vasodilation, improving exercise capacity and hemodynamics in patients with PAH.

The drug is a strong vasodilator and inhibitor of platelet aggregation. The inhalation formulation (Ventavis Inhalant Solution) was developed to replace continuous infusion prostacyclin, which was the first therapy shown to reduce mortality in patients with severe pulmonary hypertension. In nature, prostacyclin is a local hormone; intravenous introduction can result in systemic side effects and progressive tolerance, requiring more and more of the drug.

The randomized clinical trial reported for approval was conducted on 203 adult patients with PAH; 101 received inhaled iloprost, and 102 received placebo. The response rate in the iloprost group (6‐9 inhalations per day) was 19%, compared with 4% for the placebo group. The response rate was determined using a primary composite end point that incorporated improvement in exercise capacity, improvement in at least one New York Heart Association PAH class, and no death or deterioration. Adverse responses with iloprost included flushing, cough, jaw pain, and headache.

Iloprost is dispensed in single‐use glass ampules (2 mL) containing 20 mcg iloprost for inhalation via the Prodose Adaptive Aerosol Delivery system. Labeling indicated that iloprost should not be inhaled more than once every 2 hours, and the drug is not effective while a patient is sleeping. Vital signs should be monitored when initiating iloprost because of the risk of syncope.

Iloprost, though not yet commercially available in the United States, will be marketed by CoTherix Inc. as the Ventavis Inhalant Solution under exclusive contract with Schering AG, which markets the drug in Europe and Australia. CoTherix had previously received orphan drug designation for iloprost from the FDA in August 2004.

Clinical trials are underway in the United States to examine its interaction with other drug treatments for PAH, as well as for its potential as a preventive agent for lung cancer in heavy smokers.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1. Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2. Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

Although the industry's current proposal does not address the posting of historical clinical trials data, individual member companies have previously gone beyond the requirements of the position paper and included historical reporting, said Mr. Gajewski, and he believes they are likely to do so in the future.

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Big Pharma's Annus Horribilis

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the study authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors (including the editors of the Journal of the American Medical Association, the New England Journal of Medicine, and the British Medical Journal) issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Finally, problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence. The head of the agency wrote to pharmaceutical companies to demand more action on an agreement to publish clinical trial data.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1. Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2. Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

Although the industry's current proposal does not address the posting of historical clinical trials data, individual member companies have previously gone beyond the requirements of the position paper and included historical reporting, said Mr. Gajewski, and he believes they are likely to do so in the future.

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Big Pharma's Annus Horribilis

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the study authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors (including the editors of the Journal of the American Medical Association, the New England Journal of Medicine, and the British Medical Journal) issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Finally, problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence. The head of the agency wrote to pharmaceutical companies to demand more action on an agreement to publish clinical trial data.

In the face of bad publicity and impending restrictions, trade groups representing pharmaceutical companies have proposed a voluntary plan for using a clinical trials registry as well as results databases by midyear.

The “Joint Position on the Disclosure of Clinical Trial Information via Clinical Trials Registries and Databases,” issued by the Pharmaceutical Research and Manufacturers of America (PhRMA), sister organizations in Europe and Japan, and the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) covers all nonexploratory (non-phase I) clinical drug trials and has two major requirements:

1. Clinical trials registry listing. All trials initiated on or after July 1, 2005, must be included in a clinical trials registry. Trials that are now underway must be included by Sept. 13, 2005.

Each trial “should be given a unique identifier to ensure transparency of clinical trial results” that would permit tracking the trial results through multiple databases. The U.S. government's trial registry site (www.clinicaltrials.gov

2. Timely posting of results. Results for all trials completed after Jan. 6, 2005, must be posted in a timely manner, generally within 1 year after the drug is first approved and commercially available in any country, or, for trials completed after approval, within 1 year of trial completion. An exception is made if posting would compromise publication in a peer-reviewed journal.

The database should include results of all non-phase I trials “conducted on a drug that is approved for marketing and is commercially available in at least one country,” according to the proposal. Furthermore, the data must be disclosed “on a free, publicly accessible, clinical trials database, regardless of outcome.”

The deadlines for registration outlined in the proposal match the mandatory deadlines issued by the International Committee of Medical Journal Editors last September. The ICMJE will require clinical trials registration prior to publication of drug trial results in member journals (including the Journal of the American Medical Association and the New England Journal of Medicine).

This mandatory requirement was one of the reasons the pharmaceutical groups included a registry in their proposal, Maciej Gajewski, manager of health care systems issues at IFPMA, told this newspaper.

But more significantly, the trade organizations hope that a voluntary international registry and results database will preempt the efforts of individual governments to enact their own clinical trials legislation that would make it difficult for member companies to operate efficiently on a global scale, Mr. Gajewski said.

For example, legislation was introduced in both houses of the U.S. Congress last October to mandate both trial registration and data disclosure. Although the bills did not pass, proponents say that they intend to submit similar bills this year, even in the face of the new pharmaceutical industry proposal.

A significant difference in the congressional approach is the introduction of penalties for noncompliance of up to $10,000 per day. In addition, their proposed registry (which would build upon www.clinicaltrials.gov

The focus in the position paper and the ICMJE statement (and mirrored in the federal legislation) on using www.clinicaltrials.gov

In a September 2004 editorial, Kamran Abbasi, acting editor of the BMJ, called www.clinicaltrials.gov

Requiring worldwide adherence to FDA regulations also concerns the IFPMA, Mr. Gajewski said, because “more and more trials are being conducted in developing countries.”

Although the industry's current proposal does not address the posting of historical clinical trials data, individual member companies have previously gone beyond the requirements of the position paper and included historical reporting, said Mr. Gajewski, and he believes they are likely to do so in the future.

He declined to comment, however, on the next steps in moving forward with the clinical trials registration and the databases, given that some of these events involve nonpublic, industry-related issues.

Last October, PhRMA launched its own results database for use by health care professionals and the general public (www.clinicalstudyresults.org

Big Pharma's Annus Horribilis

Not everything went wrong for big pharma last year, but it might have seemed that way to some companies. Attacks came on several fronts, from journal articles to journal editors to the courts, and even legislators in the U.S. Congress and British Parliament.

In May, a report in the Journal of the American Medical Association highlighted the need for full disclosure by the industry of drug trial outcomes. An-Wen Chan, M.D., and colleagues at the Centre for Statistics and Medicine, Oxford, England, reviewed the original reports behind 122 published studies of 102 clinical trials. They found that overall, 50% of efficacy outcomes and 65% of harm outcomes per trial were incompletely reported. Furthermore, 86% (42 of 49) of trial investigators surveyed denied the existence of unreported outcomes despite clear evidence to the contrary (JAMA 2004;291:2457–65).

“The reporting of trial outcomes is not only frequently incomplete but also biased and inconsistent with protocols. Published articles, as well as reviews that incorporate them, may therefore be unreliable and overestimate the benefits of an intervention,” the study authors wrote.

In June, the American Medical Association endorsed the concept of clinical trial registration, and GlaxoSmithKline was sued by the state of New York for concealing negative information from clinical trials related to Paxil.

In August, GSK agreed to a settlement that required posting a summary on its corporate Web site of every company-sponsored drug trial completed after Dec. 27, 2000.

In September, Forest Laboratories, manufacturers of the antidepressants Lexapro (escitalopram) and Celexa (citalopram) in a separate agreement with the state of New York, said it would post clinical study results completed since Jan. 1, 2000, for its marketed drugs.

That same month, the International Committee of Medical Journal Editors (including the editors of the Journal of the American Medical Association, the New England Journal of Medicine, and the British Medical Journal) issued a requirement that clinical trials be registered by July 1, 2005, for results to be published in member journals.

Finally, problems with cyclooxygenase-2 (COX-2) drugs came to light, and Merck pulled Vioxx (rofecoxib) off the market after its own study revealed an association between the use of the drug and an increased the risk of cardiovascular events.

In October, bills were introduced (but not passed) in the U.S. Congress that would mandate registration of all clinical trials and provide penalties of up to $10,000 per day for noncompliance.

And in November 2004, the Medicines and Healthcare Products Regulatory Authority (the British version of the U.S. FDA) announced its intention to add members of the general public to its regulation of medicines committee, in part to limit industry influence. The head of the agency wrote to pharmaceutical companies to demand more action on an agreement to publish clinical trial data.

Medicare has agreed to reimburse for vertebral fracture assessment by dual-energy x-ray absorptiometry using the newly approved CPT code 76077, according to the International Society for Clinical Densitometry.

“Vertebral fractures are a powerful barometer in predicting future bone fragility in a patient,” said E. Michael Lewiecki, M.D., osteoporosis director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque, and president of the ISCD. “The new code gives physicians the opportunity to accurately evaluate a patient's future fracture risk and therefore improve the accuracy of the diagnosis.”

Previous vertebral fracture is a major risk factor for future fragility fractures. “Vertebral fractures are present in about one-third of women over age 65 and are highly related to increased fracture risk at the spine and hip independent of a patient's bone density,” according to Hologic Inc., one of two manufacturers of the dual-energy x-ray absorptiometry (DXA) systems covered under the new code.

Women with such fractures also have less ability to perform daily activities and a significantly higher morbidity, the company added.

Vertebral fracture assessment (VFA) also is a more sensitive measure of identifying osteoporosis than is bone mineral density analysis.

“Based upon BMD alone and the central site measured, 11%-18% of women with vertebral fractures would have been classified as normal,” according to Vance J. Bray, M.D., of the Denver Arthritis Clinic, in a report in the ISCD newsletter, Osteoflash. Such vertebral deformities occur in approximately 11 per 100 women aged 50-59 years and in 54 per 100 women aged 80 years and older, according to Dr. Bray.

The CPT is a continually updated listing of descriptive terms and identifying codes developed and maintained by the American Medical Association, which recently approved implementing the new CPT code for physicians to diagnose vertebral fractures.

Physicians use CPT codes to refer to (and to report providing) medical services and procedures. The CPT is the most widely accepted nomenclature used for service claims under private and public health insurance programs.

Implementation of a new code is recognition of the importance of a new procedure and a vehicle for its inclusion in insurance claims for reimbursement

The ISCD testified to the AMA about the value of this technique to facilitate approval of the new code.

The Health Insurance Portability and Accountability Act of 1996 requires that the most current code be used in all covered health care transactions, and the new code must be used for dates of service as of Jan. 1, 2005.

The Centers for Medicare and Medicaid Services reimbursement for vertebral fracture assessment is set for a national average of about $40, according to Dr. Bray.

Reimbursement for this new imaging technique recognizes its importance, according to the ISCD. “Health care providers will be able to use VFA to select those patients who are at the highest risk for fractures and structure treatment plans to be most beneficial and cost effective,” the organization said.

ISCD is developing educational programs to teach physicians high-quality acquisition and interpretation of vertebral fracture assessment using DXA technology. In February 2005, the ISCD annual meeting in New Orleans will offer an updated bone densitometry class that will incorporate 1-hour VFA introductory lectures for clinicians and technologists.

Criteria for the performance of vertebral fracture assessment are being developed by an ISCD task force and will be discussed at the 2005 ISCD Position Development Conference in Vancouver, B.C., in July, according to Dr. Bray.

DXA has been called the “gold standard” of analysis for measurement of bone mineral density and will continue to be covered by CPT code 76075 for that purpose.

Medicare has agreed to reimburse for vertebral fracture assessment by dual-energy x-ray absorptiometry using the newly approved CPT code 76077, according to the International Society for Clinical Densitometry.

“Vertebral fractures are a powerful barometer in predicting future bone fragility in a patient,” said E. Michael Lewiecki, M.D., osteoporosis director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque, and president of the ISCD. “The new code gives physicians the opportunity to accurately evaluate a patient's future fracture risk and therefore improve the accuracy of the diagnosis.”

Previous vertebral fracture is a major risk factor for future fragility fractures. “Vertebral fractures are present in about one-third of women over age 65 and are highly related to increased fracture risk at the spine and hip independent of a patient's bone density,” according to Hologic Inc., one of two manufacturers of the dual-energy x-ray absorptiometry (DXA) systems covered under the new code.

Women with such fractures also have less ability to perform daily activities and a significantly higher morbidity, the company added.

Vertebral fracture assessment (VFA) also is a more sensitive measure of identifying osteoporosis than is bone mineral density analysis.

“Based upon BMD alone and the central site measured, 11%-18% of women with vertebral fractures would have been classified as normal,” according to Vance J. Bray, M.D., of the Denver Arthritis Clinic, in a report in the ISCD newsletter, Osteoflash. Such vertebral deformities occur in approximately 11 per 100 women aged 50-59 years and in 54 per 100 women aged 80 years and older, according to Dr. Bray.

The CPT is a continually updated listing of descriptive terms and identifying codes developed and maintained by the American Medical Association, which recently approved implementing the new CPT code for physicians to diagnose vertebral fractures.

Physicians use CPT codes to refer to (and to report providing) medical services and procedures. The CPT is the most widely accepted nomenclature used for service claims under private and public health insurance programs.

Implementation of a new code is recognition of the importance of a new procedure and a vehicle for its inclusion in insurance claims for reimbursement

The ISCD testified to the AMA about the value of this technique to facilitate approval of the new code.

The Health Insurance Portability and Accountability Act of 1996 requires that the most current code be used in all covered health care transactions, and the new code must be used for dates of service as of Jan. 1, 2005.

The Centers for Medicare and Medicaid Services reimbursement for vertebral fracture assessment is set for a national average of about $40, according to Dr. Bray.

Reimbursement for this new imaging technique recognizes its importance, according to the ISCD. “Health care providers will be able to use VFA to select those patients who are at the highest risk for fractures and structure treatment plans to be most beneficial and cost effective,” the organization said.

ISCD is developing educational programs to teach physicians high-quality acquisition and interpretation of vertebral fracture assessment using DXA technology. In February 2005, the ISCD annual meeting in New Orleans will offer an updated bone densitometry class that will incorporate 1-hour VFA introductory lectures for clinicians and technologists.

Criteria for the performance of vertebral fracture assessment are being developed by an ISCD task force and will be discussed at the 2005 ISCD Position Development Conference in Vancouver, B.C., in July, according to Dr. Bray.

DXA has been called the “gold standard” of analysis for measurement of bone mineral density and will continue to be covered by CPT code 76075 for that purpose.

Medicare has agreed to reimburse for vertebral fracture assessment by dual-energy x-ray absorptiometry using the newly approved CPT code 76077, according to the International Society for Clinical Densitometry.

“Vertebral fractures are a powerful barometer in predicting future bone fragility in a patient,” said E. Michael Lewiecki, M.D., osteoporosis director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque, and president of the ISCD. “The new code gives physicians the opportunity to accurately evaluate a patient's future fracture risk and therefore improve the accuracy of the diagnosis.”

Previous vertebral fracture is a major risk factor for future fragility fractures. “Vertebral fractures are present in about one-third of women over age 65 and are highly related to increased fracture risk at the spine and hip independent of a patient's bone density,” according to Hologic Inc., one of two manufacturers of the dual-energy x-ray absorptiometry (DXA) systems covered under the new code.

Women with such fractures also have less ability to perform daily activities and a significantly higher morbidity, the company added.

Vertebral fracture assessment (VFA) also is a more sensitive measure of identifying osteoporosis than is bone mineral density analysis.

“Based upon BMD alone and the central site measured, 11%-18% of women with vertebral fractures would have been classified as normal,” according to Vance J. Bray, M.D., of the Denver Arthritis Clinic, in a report in the ISCD newsletter, Osteoflash. Such vertebral deformities occur in approximately 11 per 100 women aged 50-59 years and in 54 per 100 women aged 80 years and older, according to Dr. Bray.

The CPT is a continually updated listing of descriptive terms and identifying codes developed and maintained by the American Medical Association, which recently approved implementing the new CPT code for physicians to diagnose vertebral fractures.

Physicians use CPT codes to refer to (and to report providing) medical services and procedures. The CPT is the most widely accepted nomenclature used for service claims under private and public health insurance programs.

Implementation of a new code is recognition of the importance of a new procedure and a vehicle for its inclusion in insurance claims for reimbursement

The ISCD testified to the AMA about the value of this technique to facilitate approval of the new code.

The Health Insurance Portability and Accountability Act of 1996 requires that the most current code be used in all covered health care transactions, and the new code must be used for dates of service as of Jan. 1, 2005.

The Centers for Medicare and Medicaid Services reimbursement for vertebral fracture assessment is set for a national average of about $40, according to Dr. Bray.

Reimbursement for this new imaging technique recognizes its importance, according to the ISCD. “Health care providers will be able to use VFA to select those patients who are at the highest risk for fractures and structure treatment plans to be most beneficial and cost effective,” the organization said.

ISCD is developing educational programs to teach physicians high-quality acquisition and interpretation of vertebral fracture assessment using DXA technology. In February 2005, the ISCD annual meeting in New Orleans will offer an updated bone densitometry class that will incorporate 1-hour VFA introductory lectures for clinicians and technologists.

Criteria for the performance of vertebral fracture assessment are being developed by an ISCD task force and will be discussed at the 2005 ISCD Position Development Conference in Vancouver, B.C., in July, according to Dr. Bray.

DXA has been called the “gold standard” of analysis for measurement of bone mineral density and will continue to be covered by CPT code 76075 for that purpose.

Appreciation

Ancel Keys, Ph.D., the physiologist who became a leading authority on the role of diet in health, died on November 20 at the age of 100. His influence stretched from the skies of World War II, owing to his role in developing “K-rations” for U.S. paratroopers, to the cover of Time magazine, for his role in the discovery and popularization of the link between cholesterol and heart disease.

Dr. Keys attended the University of California, Berkeley, where he received a B.A. in economics, an M.S. in biology, and a Ph.D. in oceanography and biology. He received a second Ph.D., in physiology, from King's College, Cambridge in 1938.

Dr. Keys became a professor at the University of Minnesota in 1936, and organized what would become the Laboratory of Physiological Hygiene. He remained its director until his retirement in 1972.

Nicknamed “Mr. Cholesterol,” Dr. Keys was most noted for his “Seven Countries Study,” in which he postulated that the disparity in heart attack rates between nations was due to the influence of fat in the diets.

Finns, with the highest national heart attack, ate large quantities of animal fat and had high cholesterol levels. Cretans, with the lowest heart attack rate, ate far less fat, with olive oil the primary source, and had lower cholesterol levels. This was the first linkage between diet and coronary disease.

Such data led Dr. Keys to the development and popularization of the “Mediterranean Diet” in a series of best-selling books cowritten with his wife, Margaret Harvey, a biochemist.

Changes

Gary S. Roubin, M.D., was chosen head of the Department of Interventional Cardiology at Lenox Hill Hospital, New York. Dr. Roubin, the coinventor of the Gianturo-Roubin Flex-Stent, the first Food and Drug Administration-approved coronary artery stent, is slated to expand the new department in depth and breadth of service. This includes hiring Howard Cohen, M.D., formerly of the University of Pittsburgh, to serve as director of the heart failure and structural heart program, and Kirk Garratt, M.D., from the Mayo Clinic, who will serve as director of interventional cardiology research. Dr. Roubin returns to Lenox Hill Hospital where he was director of endovascular therapy in 1997–2003. Roubin's new team follows the departure of nine interventional cardiologists, including Jeffery Moses, M.D., former chief of interventional cardiology, who all left Lenox Hill for Columbia University in August 2004.

The Cardiovascular Research Foundation will collaborate with Columbia University Medical Center (CUMC), New York, to translate basic science into new therapies and less invasive procedures for patients with cardiovascular disease. CUMC has also created a new Center for Interventional Vascular Therapy to foster collaboration across medical subspecialties.

The Heart Rhythm Society has relocated its headquarters to Washington from Natick, Mass. “Being in Washington will help us forge stronger alliances with governing agencies and health care groups whose work complements ours,” said Stephen C. Hammill, M.D., president of the society.

Rx Briefs

The FDA issued a Class 1 recall on automated external defibrillators (AEDs) produced by the now-defunct Access CardioSystems Inc., warning customers to stop using them immediately. These devices are used by hospitals, fire departments, and emergency personnel. The AEDs were recalled because they may fail to deliver a shock due to a faulty circuit board and/or may turn on unexpectedly due to a faulty switch and fail to operate.

The ASCOT trial of Pfizer's amlodipine (Norvasc) and perindopril (Coversyl) ended early because the drugs performed so well it would have been unethical to continue, said Peter Sever, Ph.D., of Imperial College, London, cochair of the 19,000-patient study. Patients on amlodipine (calcium channel blocker) and perindopril (ACE inhibitor) had substantially fewer cardiovascular events, including heart attacks, than did those on β-blockers and diuretics.

Appreciation

Ancel Keys, Ph.D., the physiologist who became a leading authority on the role of diet in health, died on November 20 at the age of 100. His influence stretched from the skies of World War II, owing to his role in developing “K-rations” for U.S. paratroopers, to the cover of Time magazine, for his role in the discovery and popularization of the link between cholesterol and heart disease.

Dr. Keys attended the University of California, Berkeley, where he received a B.A. in economics, an M.S. in biology, and a Ph.D. in oceanography and biology. He received a second Ph.D., in physiology, from King's College, Cambridge in 1938.

Dr. Keys became a professor at the University of Minnesota in 1936, and organized what would become the Laboratory of Physiological Hygiene. He remained its director until his retirement in 1972.

Nicknamed “Mr. Cholesterol,” Dr. Keys was most noted for his “Seven Countries Study,” in which he postulated that the disparity in heart attack rates between nations was due to the influence of fat in the diets.

Finns, with the highest national heart attack, ate large quantities of animal fat and had high cholesterol levels. Cretans, with the lowest heart attack rate, ate far less fat, with olive oil the primary source, and had lower cholesterol levels. This was the first linkage between diet and coronary disease.

Such data led Dr. Keys to the development and popularization of the “Mediterranean Diet” in a series of best-selling books cowritten with his wife, Margaret Harvey, a biochemist.

Changes

Gary S. Roubin, M.D., was chosen head of the Department of Interventional Cardiology at Lenox Hill Hospital, New York. Dr. Roubin, the coinventor of the Gianturo-Roubin Flex-Stent, the first Food and Drug Administration-approved coronary artery stent, is slated to expand the new department in depth and breadth of service. This includes hiring Howard Cohen, M.D., formerly of the University of Pittsburgh, to serve as director of the heart failure and structural heart program, and Kirk Garratt, M.D., from the Mayo Clinic, who will serve as director of interventional cardiology research. Dr. Roubin returns to Lenox Hill Hospital where he was director of endovascular therapy in 1997–2003. Roubin's new team follows the departure of nine interventional cardiologists, including Jeffery Moses, M.D., former chief of interventional cardiology, who all left Lenox Hill for Columbia University in August 2004.

The Cardiovascular Research Foundation will collaborate with Columbia University Medical Center (CUMC), New York, to translate basic science into new therapies and less invasive procedures for patients with cardiovascular disease. CUMC has also created a new Center for Interventional Vascular Therapy to foster collaboration across medical subspecialties.

The Heart Rhythm Society has relocated its headquarters to Washington from Natick, Mass. “Being in Washington will help us forge stronger alliances with governing agencies and health care groups whose work complements ours,” said Stephen C. Hammill, M.D., president of the society.

Rx Briefs

The FDA issued a Class 1 recall on automated external defibrillators (AEDs) produced by the now-defunct Access CardioSystems Inc., warning customers to stop using them immediately. These devices are used by hospitals, fire departments, and emergency personnel. The AEDs were recalled because they may fail to deliver a shock due to a faulty circuit board and/or may turn on unexpectedly due to a faulty switch and fail to operate.

The ASCOT trial of Pfizer's amlodipine (Norvasc) and perindopril (Coversyl) ended early because the drugs performed so well it would have been unethical to continue, said Peter Sever, Ph.D., of Imperial College, London, cochair of the 19,000-patient study. Patients on amlodipine (calcium channel blocker) and perindopril (ACE inhibitor) had substantially fewer cardiovascular events, including heart attacks, than did those on β-blockers and diuretics.

Appreciation

Ancel Keys, Ph.D., the physiologist who became a leading authority on the role of diet in health, died on November 20 at the age of 100. His influence stretched from the skies of World War II, owing to his role in developing “K-rations” for U.S. paratroopers, to the cover of Time magazine, for his role in the discovery and popularization of the link between cholesterol and heart disease.

Dr. Keys attended the University of California, Berkeley, where he received a B.A. in economics, an M.S. in biology, and a Ph.D. in oceanography and biology. He received a second Ph.D., in physiology, from King's College, Cambridge in 1938.

Dr. Keys became a professor at the University of Minnesota in 1936, and organized what would become the Laboratory of Physiological Hygiene. He remained its director until his retirement in 1972.

Nicknamed “Mr. Cholesterol,” Dr. Keys was most noted for his “Seven Countries Study,” in which he postulated that the disparity in heart attack rates between nations was due to the influence of fat in the diets.

Finns, with the highest national heart attack, ate large quantities of animal fat and had high cholesterol levels. Cretans, with the lowest heart attack rate, ate far less fat, with olive oil the primary source, and had lower cholesterol levels. This was the first linkage between diet and coronary disease.

Such data led Dr. Keys to the development and popularization of the “Mediterranean Diet” in a series of best-selling books cowritten with his wife, Margaret Harvey, a biochemist.

Changes

Gary S. Roubin, M.D., was chosen head of the Department of Interventional Cardiology at Lenox Hill Hospital, New York. Dr. Roubin, the coinventor of the Gianturo-Roubin Flex-Stent, the first Food and Drug Administration-approved coronary artery stent, is slated to expand the new department in depth and breadth of service. This includes hiring Howard Cohen, M.D., formerly of the University of Pittsburgh, to serve as director of the heart failure and structural heart program, and Kirk Garratt, M.D., from the Mayo Clinic, who will serve as director of interventional cardiology research. Dr. Roubin returns to Lenox Hill Hospital where he was director of endovascular therapy in 1997–2003. Roubin's new team follows the departure of nine interventional cardiologists, including Jeffery Moses, M.D., former chief of interventional cardiology, who all left Lenox Hill for Columbia University in August 2004.

The Cardiovascular Research Foundation will collaborate with Columbia University Medical Center (CUMC), New York, to translate basic science into new therapies and less invasive procedures for patients with cardiovascular disease. CUMC has also created a new Center for Interventional Vascular Therapy to foster collaboration across medical subspecialties.

The Heart Rhythm Society has relocated its headquarters to Washington from Natick, Mass. “Being in Washington will help us forge stronger alliances with governing agencies and health care groups whose work complements ours,” said Stephen C. Hammill, M.D., president of the society.

Rx Briefs

The FDA issued a Class 1 recall on automated external defibrillators (AEDs) produced by the now-defunct Access CardioSystems Inc., warning customers to stop using them immediately. These devices are used by hospitals, fire departments, and emergency personnel. The AEDs were recalled because they may fail to deliver a shock due to a faulty circuit board and/or may turn on unexpectedly due to a faulty switch and fail to operate.

The ASCOT trial of Pfizer's amlodipine (Norvasc) and perindopril (Coversyl) ended early because the drugs performed so well it would have been unethical to continue, said Peter Sever, Ph.D., of Imperial College, London, cochair of the 19,000-patient study. Patients on amlodipine (calcium channel blocker) and perindopril (ACE inhibitor) had substantially fewer cardiovascular events, including heart attacks, than did those on β-blockers and diuretics.