Jennie Smith

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three – adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs £9,295 ($14,782.50) per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs £9,295 ($14,782.50) per year, assuming a 40-mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs £10,910 ($17,352.16) per year based on infusions repeated every 8 weeks (average of 6.5 doses per year), according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated £9,295 (14,782.50) per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a "significant" portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug's monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum. 2009;60:976-86). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, "the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment," and in the case of an adverse event, "it would take longer for the treatment effect to wear off."

NICE's guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three -- adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs ?9,295 per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs ?9,295 per year, assuming a 40 mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs ?10,910 per year based on infusions repeated every 8 weeks (average of 6.5 doses per year], according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated ?9,295 per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a “significant” portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug’s monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum 2009; 60: 976-986). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, “the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment,” and in the case of an adverse event, “it would take longer for the treatment effect to wear off.”

NICE’s guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three -- adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs ?9,295 per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs ?9,295 per year, assuming a 40 mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs ?10,910 per year based on infusions repeated every 8 weeks (average of 6.5 doses per year], according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated ?9,295 per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a “significant” portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug’s monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum 2009; 60: 976-986). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, “the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment,” and in the case of an adverse event, “it would take longer for the treatment effect to wear off.”

NICE’s guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

The clinical effectiveness agency for England and Wales said in draft guidance Oct. 6 that it would not recommend golimumab to treat psoriatic arthritis, saying that it was less effective than another drug in the same class, and that it may in practice be costlier than its manufacturer says.

In August, the National Institute for Health and Clinical Excellence recommended three similar drugs for adults with psoriatic arthritis who have not responded well to standard disease-modifying anti-rheumatic therapies, such as methotrexate and sulfasalazine. All three -- adalimumab, etanercept and infliximab – are TNF-inhibitors, human monoclonal antibodies that inhibit the binding of tumor necrosis factor to its receptors.

Treatment with etanercerpt (Enbrel, Wyeth Pharmaceuticals) costs ?9,295 per year assuming a 50 mg once-weekly dose (52 doses per year) or 25 mg twice-weekly dose (104 doses per year). Treatment with adalimumab (Humira, Abbot Laboratories) costs ?9,295 per year, assuming a 40 mg dose given every two weeks (26 doses per year). Treatment with infliximab (Remicade, Schering-Plough) for an adult weighing 75 kg costs ?10,910 per year based on infusions repeated every 8 weeks (average of 6.5 doses per year], according to a statement on psoriatic arthritis treatment issued by NICE in August.

Golimumab (Simponi, Schering-Plough/Centocor), also a TNF-inhibitor, is administered via monthly self-injections of 50 mg (or 100 mg for people weighing at least 100 kg). Treatment costs an estimated ?9,295 per year, on par with etanercept and adalimumab, for a normal-weight person. The NICE reviewers said, however, they believed a “significant” portion of patients would be eligible for the higher dose, which is double the cost, making cost-effectiveness estimates for golimumab less favorable.

The NICE reviewers said they did consider the drug’s monthly dosing as an advantage to patients, compared with the other TNF inhibitors. They also determined, based on the results of one Phase III manufacturer-sponsored randomized controlled trial of 405 patients, that golimumab 50 mg was effective compared with placebo (Arthritis Rheum 2009; 60: 976-986). However, a mixed treatment comparison presented by the manufacturer showed that it was not as effective as etanercept for the same patient group.

The reviewers also noted some safety concerns about golimumab, including a lack of long-term safety data; some adverse events reported in the randomized controlled trial (though the trial was not powered to detect statistically significant differences in adverse effect outcomes); and concerns related to its 12-day half life. For example, they said, “the longer retreatment interval with golimumab may result in longer periods of discomfort because of waning efficacy before retreatment,” and in the case of an adverse event, “it would take longer for the treatment effect to wear off.”

NICE’s guidance on golimumab is not yet final; the agency is accepting comments until Oct. 27.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys' and girls' drinking habits narrowed significantly, Swiss investigators report.

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find "gender and cultural convergence in drunkenness" over the 8-year period of their study, thanks in part, they wrote, to the Eastern countries' transition to market economies and the subsequent opening of their borders to "contemporary global alcohol marketing strategies that target particularly young people"(doi:10.1001/archpediatrics.2010.191).

Photo Copyright: Galina Barskaya/Fotolia.com

Results from the WHO's Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998.

Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been "really drunk," (from "never," to "once," "2 to 3 times," "4 to 10 times," or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey.

Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. "This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use," the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, "alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group" during the study period. In Eastern Europe, by contrast, "alcohol consumption might have appeared to be part of a new and attractive lifestyle element." But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, "caution should be exercised in extending these conclusions to periods before or after" the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys' and girls' drinking habits narrowed significantly, Swiss investigators report.

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find "gender and cultural convergence in drunkenness" over the 8-year period of their study, thanks in part, they wrote, to the Eastern countries' transition to market economies and the subsequent opening of their borders to "contemporary global alcohol marketing strategies that target particularly young people"(doi:10.1001/archpediatrics.2010.191).

Photo Copyright: Galina Barskaya/Fotolia.com

Results from the WHO's Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998.

Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been "really drunk," (from "never," to "once," "2 to 3 times," "4 to 10 times," or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey.

Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. "This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use," the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, "alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group" during the study period. In Eastern Europe, by contrast, "alcohol consumption might have appeared to be part of a new and attractive lifestyle element." But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, "caution should be exercised in extending these conclusions to periods before or after" the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys' and girls' drinking habits narrowed significantly, Swiss investigators report.

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find "gender and cultural convergence in drunkenness" over the 8-year period of their study, thanks in part, they wrote, to the Eastern countries' transition to market economies and the subsequent opening of their borders to "contemporary global alcohol marketing strategies that target particularly young people"(doi:10.1001/archpediatrics.2010.191).

Photo Copyright: Galina Barskaya/Fotolia.com

Results from the WHO's Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998.

Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been "really drunk," (from "never," to "once," "2 to 3 times," "4 to 10 times," or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey.

Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. "This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use," the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, "alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group" during the study period. In Eastern Europe, by contrast, "alcohol consumption might have appeared to be part of a new and attractive lifestyle element." But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, "caution should be exercised in extending these conclusions to periods before or after" the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

Teens in Eastern Europe became more prone to drunkenness in the late 1990s, while excessive alcohol consumption among Western adolescents declined, and the gap between boys’ and girls’ drinking habits narrowed significantly, Swiss investigators report.

© Galina Barskaya/Fotolia.com

Research published online Oct. 4 in Archives of Pediatrics & Adolescent Medicine used data from an ongoing cohort study coordinated by the World Health Organization that is conducted every 4 years among 11-, 13-, and 15-year-olds. Emmanuel Kuntsche, Ph.D., of the Addiction Info Switzerland, a research institute in Lausanne, and his colleagues, analyzed responses from 77,586 questionnaires completed by 15-year old students only, as drinking was deemed more likely to occur in that age group.

Dr. Kuntsche and his colleagues hypothesized that they would find “gender and cultural convergence in drunkenness” over the eight-year period of their study, thanks in part, they wrote, to the Eastern countries’ transition to market economies and the subsequent opening of their borders to “contemporary global alcohol marketing strategies that target particularly young people” (doi:10.1001/archpediatrics.2010.191).

Results from the WHO’s Health Behavior in School-Aged Children Study of 15-year-olds in 23 countries showed that in 2005 and 2006, reports of drunkenness (defined as having five or more drinks at a time) were 40% higher among teens in all seven participating Eastern European states than they had been in 1997 and 1998. Teens in the 16 Western European and North American countries, by contrast, reported 25% fewer drunken episodes over the same time span, bringing the drinking tendencies of the Eastern and Western youths closer together. For all the countries analyzed, 15-year-olds in 2005 and 2006 reported being drunk an average of two to three times in their lives.

The researchers also noted a recent gender convergence in drinking habits. Countries with increases in adolescent drunkenness saw marked increases among girls. But, in most of the Western countries where reported drunkenness decreased since 1997 and 1998, the declines were led by boys. Still in all 23 countries, with the exception of Greenland, Norway and the United Kingdom, boys continued to report more drunken episodes than girls.

Using questionnaires that asked students to estimate how many times in their lives they had ever been “really drunk,” (from “never,” to “once,” 2 to 3 times,” “4 to 10 times,” or more), Dr. Kuntsche and his colleagues found the mean frequency of self-reported drunkenness to have increased in the seven participating formerly socialist Eastern European countries by about 40% since the 1997-1998 survey. Significant increases were found for girls in all seven Eastern countries in the survey, whereas for boys the increase was significant only in Estonia, Lithuania, and the Russian Federation. In Lithuania, the frequency of drunkenness nearly doubled among both boys and girls, from 1.81 times to 3.91 times among boys and from 1.13 times to 2.80 times among girls.

In the Western countries, by contrast, reported episodes of drinking declined in 13 of 16 countries surveyed. Drunkenness decreased significantly among boys in eight countries and among girls in seven countries, the investigators found.

Among the 13 countries in which boys had earlier reported more drunkenness than girls, the decrease was greater among boys in Canada, Denmark, Germany, Greenland, Ireland, the United Kingdom, and the United States. In Finland and Sweden, where (along with Norway) girls had reported more frequent drunkenness than boys in 1997 and 1998, the decline was greater among girls. Girls continued to be drunk more often than were boys in Norway in 2005 and 2006, just as they had been before.

Though no European nations permit the sale of alcohol to 15-year-olds, the legal drinking age is usually either 16 or 18. In the United States, where the legal drinking age is 21, reported drunkenness was on the low end among the countries, with both boys and girls reporting fewer than two episodes in 2005 and 2006, both decreases from 1997 and 1998. “This trend might have been facilitated by policies that restrict marketing and access, and by the increasing development and implementation of evidence-based prevention programs targeting adolescent substance use,” the investigators wrote in their analysis.

Dr. Kuntsche and his colleagues theorized that in Western Europe and North America, “alcohol consumption and drunkenness may have lost some of their appeal to a formerly high-consuming group” during the study period. In Eastern Europe, by contrast, “alcohol consumption might have appeared to be part of a new and attractive lifestyle element.” But in general, the findings – including the narrowing gender gaps – appeared to be consistent with trends in the adult populations of the countries surveyed, the investigators noted.

The authors noted that their study relied on self reports, which are imprecise, as was their measure of drunkenness, and so results of the surveys could vary according to respondent interpretation. Also, they wrote, “caution should be exercised in extending these conclusions to periods before or after” the defined 8-year period.

The cohort study was funded by its participating countries. Neither Dr. Kuntsche nor his colleagues reported conflicts of interest.

The European Medicines Agency on Sept. 23 moved to suspend the marketing authorizations for Avandia, Avandamet, and Avaglim, antidiabetes medicines that have increasingly been linked to increased adverse cardiovascular events, including heart attacks.

Courtesy of European Association for the Study of Diabetes

Upon legislative action by the European Commission, which is expected within the next few weeks, none of the medicines, all of which contain the drug rosiglitazone and are manufactured by GlaxoSmithKline, will be available anywhere in the European Union.

The EMA’s decision was announced simultaneously to a decision by the U.S. Food and Drug Administration to severely restrict the drug in the United States, but not take it off the market altogether. In a news conference about the decision to suspend, EMA officials said that there had been extensive contact between the U.S. and European agencies on rosiglitazone, and the data used to make the decisions were the same, regardless of the different risk-management strategies adopted. 

Dr. Kristina Dunder, and the member of the EMA’s human medicines committee in charge of Avandia (rosiglitazone), Avandamet (rosiglitazone and metformin) and Avaglim (rosiglitazone and glimepiride), said that the agency, considering all available data, now estimated that the drugs were associated with 20%-40% increased risk for cardiovascular events, “depending on baselines.”

EMA officials explained that the two agencies’ different decisions on rosiglitazone were based on the legal tools available to each. “We looked at the possibility of further restricting the use of [rosiglitazone],” Dr. Hans-Georg Eichler, EMA’s senior medical officer, told reporters. Its use, however, “was already very much restricted in Europe.” After an EMA investigation revealed that despite restrictive labeling and warnings, the drug was being prescribed off-label in Europe, the agency concluded that “the best way forward was a suspension,” Dr. Eichler said.

Because the EMA stopped short of revoking the marketing authorizations for the three medicines, opting instead for the ostensibly temporary measure of suspension, the possibility that rosiglitazone might be used in clinical trials remains open. Individual European countries will have to decide whether such trials can proceed, Dr. Eichler said.

Rosiglitazone has had EU marketing authorization since 2000, though its indications have gradually been narrowed because of concerns about cardiovascular risks.

“Since its first authorization, rosiglitazone has been recognized to be associated with fluid retention and increased risk of heart failure, and its cardiovascular safety has always been kept under close review. Consequently, the use of rosiglitazone was restricted to a second-line treatment and contraindicated in patients with heart failure or a history of heart failure,” in 2000, EMA said in a news release explaining its suspension decision. “Data from clinical trials, observational studies and meta-analyses of existing studies that have become available over the last three years have suggested a possibly increased risk of ischaemic heart disease associated with the use of rosiglitazone. Further restrictions on the use of these medicines in patients with ischaemic heart disease were introduced.”

Asked why it took 10 years for the EMA to acquire sufficient data to suspend the drug, Dr. Eichler defended his agency’s actions.

“The difficulty in a situation like this is that we’re looking at a very common adverse event,” he said, saying that though the agency had received “signals” about the drug’s cardiovascular risks from the beginning, such signals were common to nearly every drug, and if heeded, “we’d probably not have a single drug for our patients on the market.”

In the case of a diabetes drug, Dr. Eichler said, it was particularly difficult to determine whether adverse cardiovascular events were the result of the drug or the disease itself. “Evidence accumulates over time, and now sufficient evidence seems to have accumulated,” he said about rosiglitazone’s risks. “Are we happy with the fact that it took 10 years? Of course not.”

Simon O’Neill, a director of care at the health charity Diabetes UK, said in a prepared statement Sept. 23 that his organization was urging people taking rosiglitazone to contact their health care providers as soon as possible, but not to stop taking the medication until meeting with them. “Patient safety is paramount, so we welcome that a decision has been made about Avandia so people can now be supported to change onto an alternative treatment,” O’Neill said. “We would urge the EMA to make swifter decisions in the future to ensure patient safety.”

In a statement released immediately after the FDA announced its decision, Dr. Steven Nissen, the author of the meta-analysis published in 2007 that found an increased risk for myocardial infarction and cardiovascular death associated with treatment, said that both the FDA and EMA decisions will result in essentially the same outcome, and predicted that Avandia “will quickly become a rarely used therapy.”

“By severely restricting access to Avandia, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive Avandia,” said Dr. Nissen, chairman of the department of Cardiovascular Medicine, Cleveland Clinic Foundation.

The European Medicines Agency on Sept. 23 moved to suspend the marketing authorizations for Avandia, Avandamet, and Avaglim, antidiabetes medicines that have increasingly been linked to increased adverse cardiovascular events, including heart attacks.

Courtesy of European Association for the Study of Diabetes

Upon legislative action by the European Commission, which is expected within the next few weeks, none of the medicines, all of which contain the drug rosiglitazone and are manufactured by GlaxoSmithKline, will be available anywhere in the European Union.

The EMA’s decision was announced simultaneously to a decision by the U.S. Food and Drug Administration to severely restrict the drug in the United States, but not take it off the market altogether. In a news conference about the decision to suspend, EMA officials said that there had been extensive contact between the U.S. and European agencies on rosiglitazone, and the data used to make the decisions were the same, regardless of the different risk-management strategies adopted. 

Dr. Kristina Dunder, and the member of the EMA’s human medicines committee in charge of Avandia (rosiglitazone), Avandamet (rosiglitazone and metformin) and Avaglim (rosiglitazone and glimepiride), said that the agency, considering all available data, now estimated that the drugs were associated with 20%-40% increased risk for cardiovascular events, “depending on baselines.”

EMA officials explained that the two agencies’ different decisions on rosiglitazone were based on the legal tools available to each. “We looked at the possibility of further restricting the use of [rosiglitazone],” Dr. Hans-Georg Eichler, EMA’s senior medical officer, told reporters. Its use, however, “was already very much restricted in Europe.” After an EMA investigation revealed that despite restrictive labeling and warnings, the drug was being prescribed off-label in Europe, the agency concluded that “the best way forward was a suspension,” Dr. Eichler said.

Because the EMA stopped short of revoking the marketing authorizations for the three medicines, opting instead for the ostensibly temporary measure of suspension, the possibility that rosiglitazone might be used in clinical trials remains open. Individual European countries will have to decide whether such trials can proceed, Dr. Eichler said.

Rosiglitazone has had EU marketing authorization since 2000, though its indications have gradually been narrowed because of concerns about cardiovascular risks.

“Since its first authorization, rosiglitazone has been recognized to be associated with fluid retention and increased risk of heart failure, and its cardiovascular safety has always been kept under close review. Consequently, the use of rosiglitazone was restricted to a second-line treatment and contraindicated in patients with heart failure or a history of heart failure,” in 2000, EMA said in a news release explaining its suspension decision. “Data from clinical trials, observational studies and meta-analyses of existing studies that have become available over the last three years have suggested a possibly increased risk of ischaemic heart disease associated with the use of rosiglitazone. Further restrictions on the use of these medicines in patients with ischaemic heart disease were introduced.”

Asked why it took 10 years for the EMA to acquire sufficient data to suspend the drug, Dr. Eichler defended his agency’s actions.

“The difficulty in a situation like this is that we’re looking at a very common adverse event,” he said, saying that though the agency had received “signals” about the drug’s cardiovascular risks from the beginning, such signals were common to nearly every drug, and if heeded, “we’d probably not have a single drug for our patients on the market.”

In the case of a diabetes drug, Dr. Eichler said, it was particularly difficult to determine whether adverse cardiovascular events were the result of the drug or the disease itself. “Evidence accumulates over time, and now sufficient evidence seems to have accumulated,” he said about rosiglitazone’s risks. “Are we happy with the fact that it took 10 years? Of course not.”

Simon O’Neill, a director of care at the health charity Diabetes UK, said in a prepared statement Sept. 23 that his organization was urging people taking rosiglitazone to contact their health care providers as soon as possible, but not to stop taking the medication until meeting with them. “Patient safety is paramount, so we welcome that a decision has been made about Avandia so people can now be supported to change onto an alternative treatment,” O’Neill said. “We would urge the EMA to make swifter decisions in the future to ensure patient safety.”

In a statement released immediately after the FDA announced its decision, Dr. Steven Nissen, the author of the meta-analysis published in 2007 that found an increased risk for myocardial infarction and cardiovascular death associated with treatment, said that both the FDA and EMA decisions will result in essentially the same outcome, and predicted that Avandia “will quickly become a rarely used therapy.”

“By severely restricting access to Avandia, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive Avandia,” said Dr. Nissen, chairman of the department of Cardiovascular Medicine, Cleveland Clinic Foundation.

The European Medicines Agency on Sept. 23 moved to suspend the marketing authorizations for Avandia, Avandamet, and Avaglim, antidiabetes medicines that have increasingly been linked to increased adverse cardiovascular events, including heart attacks.

Courtesy of European Association for the Study of Diabetes

Upon legislative action by the European Commission, which is expected within the next few weeks, none of the medicines, all of which contain the drug rosiglitazone and are manufactured by GlaxoSmithKline, will be available anywhere in the European Union.

The EMA’s decision was announced simultaneously to a decision by the U.S. Food and Drug Administration to severely restrict the drug in the United States, but not take it off the market altogether. In a news conference about the decision to suspend, EMA officials said that there had been extensive contact between the U.S. and European agencies on rosiglitazone, and the data used to make the decisions were the same, regardless of the different risk-management strategies adopted. 

Dr. Kristina Dunder, and the member of the EMA’s human medicines committee in charge of Avandia (rosiglitazone), Avandamet (rosiglitazone and metformin) and Avaglim (rosiglitazone and glimepiride), said that the agency, considering all available data, now estimated that the drugs were associated with 20%-40% increased risk for cardiovascular events, “depending on baselines.”

EMA officials explained that the two agencies’ different decisions on rosiglitazone were based on the legal tools available to each. “We looked at the possibility of further restricting the use of [rosiglitazone],” Dr. Hans-Georg Eichler, EMA’s senior medical officer, told reporters. Its use, however, “was already very much restricted in Europe.” After an EMA investigation revealed that despite restrictive labeling and warnings, the drug was being prescribed off-label in Europe, the agency concluded that “the best way forward was a suspension,” Dr. Eichler said.

Because the EMA stopped short of revoking the marketing authorizations for the three medicines, opting instead for the ostensibly temporary measure of suspension, the possibility that rosiglitazone might be used in clinical trials remains open. Individual European countries will have to decide whether such trials can proceed, Dr. Eichler said.

Rosiglitazone has had EU marketing authorization since 2000, though its indications have gradually been narrowed because of concerns about cardiovascular risks.

“Since its first authorization, rosiglitazone has been recognized to be associated with fluid retention and increased risk of heart failure, and its cardiovascular safety has always been kept under close review. Consequently, the use of rosiglitazone was restricted to a second-line treatment and contraindicated in patients with heart failure or a history of heart failure,” in 2000, EMA said in a news release explaining its suspension decision. “Data from clinical trials, observational studies and meta-analyses of existing studies that have become available over the last three years have suggested a possibly increased risk of ischaemic heart disease associated with the use of rosiglitazone. Further restrictions on the use of these medicines in patients with ischaemic heart disease were introduced.”

Asked why it took 10 years for the EMA to acquire sufficient data to suspend the drug, Dr. Eichler defended his agency’s actions.

“The difficulty in a situation like this is that we’re looking at a very common adverse event,” he said, saying that though the agency had received “signals” about the drug’s cardiovascular risks from the beginning, such signals were common to nearly every drug, and if heeded, “we’d probably not have a single drug for our patients on the market.”

In the case of a diabetes drug, Dr. Eichler said, it was particularly difficult to determine whether adverse cardiovascular events were the result of the drug or the disease itself. “Evidence accumulates over time, and now sufficient evidence seems to have accumulated,” he said about rosiglitazone’s risks. “Are we happy with the fact that it took 10 years? Of course not.”

Simon O’Neill, a director of care at the health charity Diabetes UK, said in a prepared statement Sept. 23 that his organization was urging people taking rosiglitazone to contact their health care providers as soon as possible, but not to stop taking the medication until meeting with them. “Patient safety is paramount, so we welcome that a decision has been made about Avandia so people can now be supported to change onto an alternative treatment,” O’Neill said. “We would urge the EMA to make swifter decisions in the future to ensure patient safety.”

In a statement released immediately after the FDA announced its decision, Dr. Steven Nissen, the author of the meta-analysis published in 2007 that found an increased risk for myocardial infarction and cardiovascular death associated with treatment, said that both the FDA and EMA decisions will result in essentially the same outcome, and predicted that Avandia “will quickly become a rarely used therapy.”

“By severely restricting access to Avandia, the FDA is ensuring that only a few individuals in America will continue to take this drug. Only those patients who have failed to respond to all other therapies will be eligible to receive Avandia,” said Dr. Nissen, chairman of the department of Cardiovascular Medicine, Cleveland Clinic Foundation.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

A vaginal gel containing the microbicide PRO2000 failed to prevent HIV transmission, according to results from a randomized, controlled trial that enrolled more than 9,000 African women who inserted either PRO2000 or a placebo gel before having sex. The results were published Sept. 20 by the Lancet.

But the phase III trial’s lead investigator said that some of the lessons learned during the trial bode well for anti-HIV gels at a time when more effective ones are being tested, and that the failure of one agent shouldn’t be confused with the failure of gels as a prevention strategy – not least because women like using them. (Lancet 2010 Sept. 20 [doi:10.1016/S0140-6736(10)61086-0]).

For their research, Sheena McCormack of the U.K. Medical Research Council’s Clinical Trials Unit, in London, and colleagues, randomized 9,385 women aged 18-45 years (16 years and older in two countries) from 13 clinics in Tanzania, Zambia, Uganda, and South Africa to receive prefilled vaginal applicators with gel containing PRO2000 2%, PRO2000 0.5%, or placebo (ratio, 1:1:1). Professional sex workers (or women who are likely to have sex more than 14 times a week) and pregnant women were not enrolled. All women were HIV negative at enrollment; all were instructed to insert the gel before sexual intercourse.

The results showed that although compliance with the gel regimen was nearly 90% (measured in part by the return of used applicators), neither concentration of PRO2000 was more effective than was placebo in preventing new HIV infections after a year of use.

PRO2000, a synthetic naphthalene sulphonate polymer, had been shown to prevent HIV transmission in primate trials, and data from a smaller and unrelated study (presented in Montreal at the 2009 conference on retroviruses and opportunistic infections) had shown a 30% reduction in infections with the 0.5% concentration of PRO2000, compared with placebo, a statistically insignificant but promising result.

Dr. McCormack and colleagues’ interim trial results had shown that 2% PRO2000, the higher of the two concentrations tested, was ineffective as early as 2008, when the 2% arm of the trial was discontinued. However, the investigators had hypothesized that the higher-concentration gel might prove to be the less effective because of its potential to irritate the vagina, undermining some of its potential protective effect.

At the study’s end, the less-concentrated gel also disappointed, with the incidence of new HIV infections per 100 woman-years at 4.5 for 0.5% PRO2000 and 4.3 for placebo. Although it had biological potency in the lab, “it seemed that the most likely explanation is that the ejaculate disturbs the equilibrium in some way,” precluding PRO2000’s effectiveness, Dr. McCormack said in an interview.

But even though the final results were a surprise and a letdown, Dr. McCormack said, much was learned during the trial that could prove to be good omens for a gel containing the antiretroviral drug tenofovir. In interim results from an ongoing South African trial (n = 889) released in July (Science 2010 July 19 [doi:10.1126/science.1193748]), tenofovir 1% vaginal gel, used before sex, was shown to reduce a woman’s risk of HIV infection by 39%. Women who used the gel 80% of the time saw a 54% reduction in HIV infections.

Dr. McCormack’s group saw more than 80% compliance in the PRO2000 study, and found that – despite reports of some mild adverse effects, such as itching, in both the treatment and placebo arms – women generally reported that they enjoyed using the gel, “and a portion raved about it,” Dr. McCormack said. “Adherence around the sex act has been very good,” comparing favorably with condom use, which was found to be very low among enrollees in some of the trial countries.

The popularity of the gels would seem auspicious for an effective one, but Dr. McCormack, who is struggling to raise funds for a new study involving tenofovir gel, said she feared a waning of donor interest in vaginal gels – many of which have been disappointments – at the time when a truly effective antitransmission agent seems to have finally been discovered. This month, the New York Times reported that the U.K. government, which funded much of Dr. McCormack’s study and contributed to other gel trials, had become noncommittal on its plans to fund further research into gels.

“I am anxious not to confuse the results of our trial with [the tenofovir trial]. PRO2000 is much less potent than tenofovir,” Dr. McCormack said. “You’ve got to think about this in a bigger picture: At the moment, there’s a real possibility in tenofovir gel.”

Dr. McCormack’s study was funded by the U.K. government, the European and Developing Countries Clinical Trials Partnership, the International Partnership for Microbicides, and Endo Pharmaceuticals, the manufacturer of PRO2000, which donated the gels for the study. One coauthor of the study was an employee of Endo Pharmaceuticals with an equity interest in the company.

Neither glucosamine nor chondroitin, alone or combined, reduced joint pain or preserved joint space, according to Swiss researchers, who conclude that these supplements should not be prescribed, and if they are, health authorities and insurers should not cover them.

Meanwhile, despite a growing body of recent evidence showing the popular supplements to be ineffective, global sales of glucosamine and chondroitin have more than doubled since 2003. As of 2008, the sales of these supplements approached $2 billion and are projected to reach $2.3 billion in 2013, according to the same research team, which published its findings – from a meta-analysis of data from 10 randomized, controlled trials -- online Sept. 17 in the British Medical Journal.

The paradox of a market for a medication growing as its evidence base shrinks is probably merely the result of a predictable delay between evidence and adoption, said Dr. Peter Jüni, an epidemiologist at the University of Bern (Switzerland), lead author of the study.

High-quality evidence from large randomized controlled trials is relatively recent in the field of osteoarthritis, Dr. Jüni said in an interview, Sept. 17. “Only in the last 5-10 years has it become established in this field to do large-scale clinical trials,” he said. Of the 10 published randomized placebo-controlled trials Dr. Jüni and colleagues identified for their analysis, one was published in 1994 and the rest in the past decade, with the most recent in 2008.

“At the end of the 1990s and beginning of the 2000s, there were moderately small studies that actually made it into meta-analysis and into treatment guidelines” showing favorable results from glucosamine and chondroitin,” Dr. Jüni said. “Physicians were very reluctant to accept these then.” Eventually, of course, they did, and now “it will take time for the bad news to sink in, just as it took time for the good news in the 1990s.” Currently, Dr. Jüni noted, two more large nonindustry trials of glucosamine and chondroitin are underway. These “could put the nail in the coffin – or, you never know, could re-open the book.”

For their research, Dr. Jüni and colleagues analyzed results from randomized, placebo-controlled trials – seven of them industry-sponsored – enrolling 200 or more patients with knee or hip osteoarthritis (3,803 patients total). Using complex statistical modeling that allowed for comparisons at varied time points, the team assessed changes in levels of perceived pain after patients took glucosamine, chondroitin, or placebo daily for between 1 and 36 months. Six of the trials also measured joint narrowing (BMJ 2010;341:c4675[doi:10.1136/bmj.c4675]).

The 10 trials differed significantly in design. The majority enrolled patients with osteoarthritis on the knee only, though one enrolled patients with osteoarthritis of the hip or knee, and another included just patients with osteoarthritis of the hip. Supplements used included glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, and combinations of these. All the glucosamine supplements were tested at 1,500 mg daily, while the chondroitin supplements varied between 800 and 1,200 mg daily.

Some of the trials took place in the United States, where supplements are not standardized for quality, and some in Europe, where they are. In eight, the supplements were evaluated to ensure correct concentrations of glucosamine or chondroitin, and in two the quality of the supplements was unclear. Patients ranged in age from 58 to 66 years, and the median percentage of women participants was 68%.

On a 10-cm visual analogue scale, Dr. Jüni and colleagues found, the overall difference in pain intensity compared with placebo was -0.4 cm (95% confidence interval, -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. “For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference,” the investigators wrote. “The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero.”

The seven industry-sponsored trials were more likely to detect an effect, however limited, than the non-industry trials (P = .02 for interaction). In industry independent trials, estimated treatment effects “were minute to zero and by no means clinically relevant,” Dr. Jüni and colleagues wrote in their analysis.

A possible reason that glucosamine and chondroitin are perceived widely as effective, Dr. Jüni said, is because osteoarthritic pain tends to fluctuate naturally. If people take a supplement when their symptoms are worse, “it leads you to perceive that it works perfectly” as they gradually subside, and the theoretical mechanism of the supplement is biologically plausible. In the end, he said, it may come down to need – as much as 30% of the adult population suffers joint pain, he said, glucosamine and chondroitin are demonstrably safe, and there are few truly safe long-term treatments for joint pain.

The study was funded by grants from the Swiss National Science Foundation’s National Research Program. Neither Dr. Jüni nor any of his colleagues declared conflicts of interest.

Neither glucosamine nor chondroitin, alone or combined, reduced joint pain or preserved joint space, according to Swiss researchers, who conclude that these supplements should not be prescribed, and if they are, health authorities and insurers should not cover them.

Meanwhile, despite a growing body of recent evidence showing the popular supplements to be ineffective, global sales of glucosamine and chondroitin have more than doubled since 2003. As of 2008, the sales of these supplements approached $2 billion and are projected to reach $2.3 billion in 2013, according to the same research team, which published its findings – from a meta-analysis of data from 10 randomized, controlled trials -- online Sept. 17 in the British Medical Journal.

The paradox of a market for a medication growing as its evidence base shrinks is probably merely the result of a predictable delay between evidence and adoption, said Dr. Peter Jüni, an epidemiologist at the University of Bern (Switzerland), lead author of the study.

High-quality evidence from large randomized controlled trials is relatively recent in the field of osteoarthritis, Dr. Jüni said in an interview, Sept. 17. “Only in the last 5-10 years has it become established in this field to do large-scale clinical trials,” he said. Of the 10 published randomized placebo-controlled trials Dr. Jüni and colleagues identified for their analysis, one was published in 1994 and the rest in the past decade, with the most recent in 2008.

“At the end of the 1990s and beginning of the 2000s, there were moderately small studies that actually made it into meta-analysis and into treatment guidelines” showing favorable results from glucosamine and chondroitin,” Dr. Jüni said. “Physicians were very reluctant to accept these then.” Eventually, of course, they did, and now “it will take time for the bad news to sink in, just as it took time for the good news in the 1990s.” Currently, Dr. Jüni noted, two more large nonindustry trials of glucosamine and chondroitin are underway. These “could put the nail in the coffin – or, you never know, could re-open the book.”

For their research, Dr. Jüni and colleagues analyzed results from randomized, placebo-controlled trials – seven of them industry-sponsored – enrolling 200 or more patients with knee or hip osteoarthritis (3,803 patients total). Using complex statistical modeling that allowed for comparisons at varied time points, the team assessed changes in levels of perceived pain after patients took glucosamine, chondroitin, or placebo daily for between 1 and 36 months. Six of the trials also measured joint narrowing (BMJ 2010;341:c4675[doi:10.1136/bmj.c4675]).

The 10 trials differed significantly in design. The majority enrolled patients with osteoarthritis on the knee only, though one enrolled patients with osteoarthritis of the hip or knee, and another included just patients with osteoarthritis of the hip. Supplements used included glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, and combinations of these. All the glucosamine supplements were tested at 1,500 mg daily, while the chondroitin supplements varied between 800 and 1,200 mg daily.

Some of the trials took place in the United States, where supplements are not standardized for quality, and some in Europe, where they are. In eight, the supplements were evaluated to ensure correct concentrations of glucosamine or chondroitin, and in two the quality of the supplements was unclear. Patients ranged in age from 58 to 66 years, and the median percentage of women participants was 68%.

On a 10-cm visual analogue scale, Dr. Jüni and colleagues found, the overall difference in pain intensity compared with placebo was -0.4 cm (95% confidence interval, -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. “For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference,” the investigators wrote. “The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero.”

The seven industry-sponsored trials were more likely to detect an effect, however limited, than the non-industry trials (P = .02 for interaction). In industry independent trials, estimated treatment effects “were minute to zero and by no means clinically relevant,” Dr. Jüni and colleagues wrote in their analysis.

A possible reason that glucosamine and chondroitin are perceived widely as effective, Dr. Jüni said, is because osteoarthritic pain tends to fluctuate naturally. If people take a supplement when their symptoms are worse, “it leads you to perceive that it works perfectly” as they gradually subside, and the theoretical mechanism of the supplement is biologically plausible. In the end, he said, it may come down to need – as much as 30% of the adult population suffers joint pain, he said, glucosamine and chondroitin are demonstrably safe, and there are few truly safe long-term treatments for joint pain.

The study was funded by grants from the Swiss National Science Foundation’s National Research Program. Neither Dr. Jüni nor any of his colleagues declared conflicts of interest.

Neither glucosamine nor chondroitin, alone or combined, reduced joint pain or preserved joint space, according to Swiss researchers, who conclude that these supplements should not be prescribed, and if they are, health authorities and insurers should not cover them.

Meanwhile, despite a growing body of recent evidence showing the popular supplements to be ineffective, global sales of glucosamine and chondroitin have more than doubled since 2003. As of 2008, the sales of these supplements approached $2 billion and are projected to reach $2.3 billion in 2013, according to the same research team, which published its findings – from a meta-analysis of data from 10 randomized, controlled trials -- online Sept. 17 in the British Medical Journal.

The paradox of a market for a medication growing as its evidence base shrinks is probably merely the result of a predictable delay between evidence and adoption, said Dr. Peter Jüni, an epidemiologist at the University of Bern (Switzerland), lead author of the study.

High-quality evidence from large randomized controlled trials is relatively recent in the field of osteoarthritis, Dr. Jüni said in an interview, Sept. 17. “Only in the last 5-10 years has it become established in this field to do large-scale clinical trials,” he said. Of the 10 published randomized placebo-controlled trials Dr. Jüni and colleagues identified for their analysis, one was published in 1994 and the rest in the past decade, with the most recent in 2008.

“At the end of the 1990s and beginning of the 2000s, there were moderately small studies that actually made it into meta-analysis and into treatment guidelines” showing favorable results from glucosamine and chondroitin,” Dr. Jüni said. “Physicians were very reluctant to accept these then.” Eventually, of course, they did, and now “it will take time for the bad news to sink in, just as it took time for the good news in the 1990s.” Currently, Dr. Jüni noted, two more large nonindustry trials of glucosamine and chondroitin are underway. These “could put the nail in the coffin – or, you never know, could re-open the book.”

For their research, Dr. Jüni and colleagues analyzed results from randomized, placebo-controlled trials – seven of them industry-sponsored – enrolling 200 or more patients with knee or hip osteoarthritis (3,803 patients total). Using complex statistical modeling that allowed for comparisons at varied time points, the team assessed changes in levels of perceived pain after patients took glucosamine, chondroitin, or placebo daily for between 1 and 36 months. Six of the trials also measured joint narrowing (BMJ 2010;341:c4675[doi:10.1136/bmj.c4675]).

The 10 trials differed significantly in design. The majority enrolled patients with osteoarthritis on the knee only, though one enrolled patients with osteoarthritis of the hip or knee, and another included just patients with osteoarthritis of the hip. Supplements used included glucosamine sulfate, glucosamine hydrochloride, chondroitin sulfate, and combinations of these. All the glucosamine supplements were tested at 1,500 mg daily, while the chondroitin supplements varied between 800 and 1,200 mg daily.

Some of the trials took place in the United States, where supplements are not standardized for quality, and some in Europe, where they are. In eight, the supplements were evaluated to ensure correct concentrations of glucosamine or chondroitin, and in two the quality of the supplements was unclear. Patients ranged in age from 58 to 66 years, and the median percentage of women participants was 68%.

On a 10-cm visual analogue scale, Dr. Jüni and colleagues found, the overall difference in pain intensity compared with placebo was -0.4 cm (95% confidence interval, -0.7 to -0.1 cm) for glucosamine, -0.3 cm (-0.7 to 0.0 cm) for chondroitin, and -0.5 cm (-0.9 to 0.0 cm) for the combination. “For none of the estimates did the 95% credible intervals cross the boundary of the minimal clinically important difference,” the investigators wrote. “The differences in changes in minimal width of joint space were all minute, with 95% credible intervals overlapping zero.”

The seven industry-sponsored trials were more likely to detect an effect, however limited, than the non-industry trials (P = .02 for interaction). In industry independent trials, estimated treatment effects “were minute to zero and by no means clinically relevant,” Dr. Jüni and colleagues wrote in their analysis.

A possible reason that glucosamine and chondroitin are perceived widely as effective, Dr. Jüni said, is because osteoarthritic pain tends to fluctuate naturally. If people take a supplement when their symptoms are worse, “it leads you to perceive that it works perfectly” as they gradually subside, and the theoretical mechanism of the supplement is biologically plausible. In the end, he said, it may come down to need – as much as 30% of the adult population suffers joint pain, he said, glucosamine and chondroitin are demonstrably safe, and there are few truly safe long-term treatments for joint pain.

The study was funded by grants from the Swiss National Science Foundation’s National Research Program. Neither Dr. Jüni nor any of his colleagues declared conflicts of interest.

The National Institute for Health and Clinical Excellence said September 9 that not enough bariatric surgery is being performed in England. The agency cited a report commissioned by the Royal College of Surgeons, showing that only a small fraction of people eligible for weight loss surgery in England are actually receiving it.

About a quarter of Britons are obese, with obesity a rising trend despite numerous public health campaigns aimed at addressing it. Obesity-related disorders cost the National Health Service an estimated £4.3 billion annually, according to the U.K. Department of Health. Yet the report commissioned by the surgeons warns that English primary care trusts (PCT) are not following established clinical guidelines on bariatric surgery, which, if followed, would reduce health care costs systematically.

“If NICE guidelines on bariatric surgery were followed, direct NHS cost savings would be around £56 million a year,” NICE said in a press statement about the report. “PCTs are either ignoring NICE guidelines and rationing care for all but the most severely ill patients, or offering no service at all.”

The NICE statement stood in some contrast to the U.K. Department of Health’s response to the report, in which Public Health Minister Anne Milton said surgery “should always be a last resort” and that “it is up to individual trusts to commission a range of services to meet their local community’s needs.”

NICE officials contacted said they refused to speculate as to why their agency’s obesity guideline wasn’t being followed. However, the agency’s clinical guidelines, which include its obesity and bariatric surgery guideline, differ from its technical appraisals in that PCTs are not mandated to adhere to them.

The surgeons’ report – carried out by the Office of Health Economics, an independent research firm, and published Sept 8. – estimated that as many as many as 140,000 people in England qualified for bariatric surgery in 2009 and 2010 under guidelines published by NICE. Yet the actual number of surgeries performed at trusts in England in that time period was 3,607. This, the report concluded, was largely the result of different practices among different primary care trusts: “Adherence is generally sub-optimal but the number of procedures commissioned by PCTs ranged from one to 194 in 2009-10,” the report stated, “indicating a wide variation in practice.”

The 2006 NICE clinical guideline on obesity offers tiered recommendations on interventions based on the severity of a patient’s disease and the presence of comorbidities, with surgery as a last option following lifestyle and other interventions. According to the guideline, people with a body mass index of 40 or higher, and who have failed to lose weight through other means, qualify for surgery. People with a body mass index as low as 35 may quality for surgery if they have comorbidities, such as diabetes or high blood pressure.

Yet the trusts themselves seem to have decided to make surgery rarer, implementing the guidelines more stringently, according to the surgeons’ report, which used findings from other reports, a self-reported questionnaire to all 152 PCTs in England about their practices (81 responses were considered in the analysis), and additional records to gain a picture of how much bariatric surgery was really being performed.

The surveys revealed that the self-rationing was likely to continue in the current cost-cutting mood: “Although only one in ten PCTs that responded said that they would be reducing funding for obesity services, one third said that they would be applying the NICE guidance more stringently and none that the guidance would be applied less stringently,” the report said.

The National Institute for Health and Clinical Excellence said September 9 that not enough bariatric surgery is being performed in England. The agency cited a report commissioned by the Royal College of Surgeons, showing that only a small fraction of people eligible for weight loss surgery in England are actually receiving it.

About a quarter of Britons are obese, with obesity a rising trend despite numerous public health campaigns aimed at addressing it. Obesity-related disorders cost the National Health Service an estimated £4.3 billion annually, according to the U.K. Department of Health. Yet the report commissioned by the surgeons warns that English primary care trusts (PCT) are not following established clinical guidelines on bariatric surgery, which, if followed, would reduce health care costs systematically.

“If NICE guidelines on bariatric surgery were followed, direct NHS cost savings would be around £56 million a year,” NICE said in a press statement about the report. “PCTs are either ignoring NICE guidelines and rationing care for all but the most severely ill patients, or offering no service at all.”

The NICE statement stood in some contrast to the U.K. Department of Health’s response to the report, in which Public Health Minister Anne Milton said surgery “should always be a last resort” and that “it is up to individual trusts to commission a range of services to meet their local community’s needs.”

NICE officials contacted said they refused to speculate as to why their agency’s obesity guideline wasn’t being followed. However, the agency’s clinical guidelines, which include its obesity and bariatric surgery guideline, differ from its technical appraisals in that PCTs are not mandated to adhere to them.

The surgeons’ report – carried out by the Office of Health Economics, an independent research firm, and published Sept 8. – estimated that as many as many as 140,000 people in England qualified for bariatric surgery in 2009 and 2010 under guidelines published by NICE. Yet the actual number of surgeries performed at trusts in England in that time period was 3,607. This, the report concluded, was largely the result of different practices among different primary care trusts: “Adherence is generally sub-optimal but the number of procedures commissioned by PCTs ranged from one to 194 in 2009-10,” the report stated, “indicating a wide variation in practice.”

The 2006 NICE clinical guideline on obesity offers tiered recommendations on interventions based on the severity of a patient’s disease and the presence of comorbidities, with surgery as a last option following lifestyle and other interventions. According to the guideline, people with a body mass index of 40 or higher, and who have failed to lose weight through other means, qualify for surgery. People with a body mass index as low as 35 may quality for surgery if they have comorbidities, such as diabetes or high blood pressure.

Yet the trusts themselves seem to have decided to make surgery rarer, implementing the guidelines more stringently, according to the surgeons’ report, which used findings from other reports, a self-reported questionnaire to all 152 PCTs in England about their practices (81 responses were considered in the analysis), and additional records to gain a picture of how much bariatric surgery was really being performed.

The surveys revealed that the self-rationing was likely to continue in the current cost-cutting mood: “Although only one in ten PCTs that responded said that they would be reducing funding for obesity services, one third said that they would be applying the NICE guidance more stringently and none that the guidance would be applied less stringently,” the report said.

The National Institute for Health and Clinical Excellence said September 9 that not enough bariatric surgery is being performed in England. The agency cited a report commissioned by the Royal College of Surgeons, showing that only a small fraction of people eligible for weight loss surgery in England are actually receiving it.

About a quarter of Britons are obese, with obesity a rising trend despite numerous public health campaigns aimed at addressing it. Obesity-related disorders cost the National Health Service an estimated £4.3 billion annually, according to the U.K. Department of Health. Yet the report commissioned by the surgeons warns that English primary care trusts (PCT) are not following established clinical guidelines on bariatric surgery, which, if followed, would reduce health care costs systematically.

“If NICE guidelines on bariatric surgery were followed, direct NHS cost savings would be around £56 million a year,” NICE said in a press statement about the report. “PCTs are either ignoring NICE guidelines and rationing care for all but the most severely ill patients, or offering no service at all.”

The NICE statement stood in some contrast to the U.K. Department of Health’s response to the report, in which Public Health Minister Anne Milton said surgery “should always be a last resort” and that “it is up to individual trusts to commission a range of services to meet their local community’s needs.”

NICE officials contacted said they refused to speculate as to why their agency’s obesity guideline wasn’t being followed. However, the agency’s clinical guidelines, which include its obesity and bariatric surgery guideline, differ from its technical appraisals in that PCTs are not mandated to adhere to them.

The surgeons’ report – carried out by the Office of Health Economics, an independent research firm, and published Sept 8. – estimated that as many as many as 140,000 people in England qualified for bariatric surgery in 2009 and 2010 under guidelines published by NICE. Yet the actual number of surgeries performed at trusts in England in that time period was 3,607. This, the report concluded, was largely the result of different practices among different primary care trusts: “Adherence is generally sub-optimal but the number of procedures commissioned by PCTs ranged from one to 194 in 2009-10,” the report stated, “indicating a wide variation in practice.”

The 2006 NICE clinical guideline on obesity offers tiered recommendations on interventions based on the severity of a patient’s disease and the presence of comorbidities, with surgery as a last option following lifestyle and other interventions. According to the guideline, people with a body mass index of 40 or higher, and who have failed to lose weight through other means, qualify for surgery. People with a body mass index as low as 35 may quality for surgery if they have comorbidities, such as diabetes or high blood pressure.

Yet the trusts themselves seem to have decided to make surgery rarer, implementing the guidelines more stringently, according to the surgeons’ report, which used findings from other reports, a self-reported questionnaire to all 152 PCTs in England about their practices (81 responses were considered in the analysis), and additional records to gain a picture of how much bariatric surgery was really being performed.

The surveys revealed that the self-rationing was likely to continue in the current cost-cutting mood: “Although only one in ten PCTs that responded said that they would be reducing funding for obesity services, one third said that they would be applying the NICE guidance more stringently and none that the guidance would be applied less stringently,” the report said.