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AAP advises moderate physical, cognitive activity after sports concussion
according to a new clinical report from the American Academy of Pediatrics.
The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.
The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.
“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.
“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.
The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.
Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.
Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.
Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.
“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.
“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.
Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.
“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.
More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.
In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”
Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.
SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.
according to a new clinical report from the American Academy of Pediatrics.
The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.
The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.
“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.
“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.
The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.
Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.
Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.
Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.
“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.
“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.
Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.
“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.
More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.
In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”
Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.
SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.
according to a new clinical report from the American Academy of Pediatrics.
The update to the 2010 guidelines was needed to reflect the latest research “and it was necessary to provide this new information to guide pediatricians in evaluating and treating concussions they may see in their practice,” Mark Halstead, MD, of Washington University, St. Louis, said in an interview.
The biggest changes to the guidelines involve management of concussion, noted Dr. Halstead, who was a coauthor of the AAP clinical report. “The previous recommendation called for cognitive and physical rest, which unfortunately was interpreted as complete removal from all physical activity and limiting many other things including electronic use.
“Because of research that has been conducted since the original report, it has been shown that starting some light physical activity to increase heart rate, provided it does not worsen symptoms, can be beneficial in recovery. Also, the recommendation for complete removal of electronics and computer use has unfortunately created some issues with kids getting socially isolated,” he added.
“For better or for worse, kids are connected through their electronic devices. Removing them, with no evidence that it worsens the concussion, essentially punishes kids for their injury. We also are trying to discourage prolonged removal of kids from school,” Dr. Halstead emphasized.
The new recommendations emphasize the unique nature of sports-related concussion (SRC) from one individual to another, and the need for individualized management.
Symptoms of SRC fall into five categories, according to the guidelines: somatic, vestibular, oculomotor, cognitive, and emotional/sleep. Pediatric health care providers should rule out more severe head injuries and recognize that concussion symptoms are nonspecific and may reflect preexisting conditions, such as migraine or headache disorders, learning disorders, ADHD, mental health conditions, or sleep disorders.
Use of assessments such as the Sport Concussion Management Tool (SCAT5 for 13 years and older or Child SCAT5 for 5-12 years) can help guide clinicians, but should not be used in isolation to diagnose a concussion, the guideline authors wrote.
Strategies for injury prevention are included in the guidelines as well, such as the use of appropriate headgear. As for management, computerized neurocognitive testing can play a role in decisions regarding return to play, but should not be used in isolation.
“The biggest thing we are lacking is an objective diagnostic test to determine the presence of a concussion or its resolution,” coauthor Kody A. Moffatt, MD, of Creighton University, Omaha, Nebraska, said in an interview.
“Mandatory baseline and postinjury computerized neurocognitive testing is not recommended,” he added.
Clinicians can best manage SRC with prompt recognition and diagnosis using the available tools, followed by relative rest and return to school, then noncontact physical activities, and eventually a return to sport if appropriate.
“Most concussions in children and adolescents will resolve within 4 weeks as long as there is not additional injury to the brain during that time,” Dr. Moffat said.
More research is needed in particular about concussions in elementary and middle school children, Dr. Halstead added.
In the meantime, the take-home message to pediatricians for managing SRC is one of common sense. “Extremes of removing all stimulus from a child is not likely to get them better sooner and research suggests may take them longer to get better,” Dr. Halstead noted. “That doesn’t mean they don’t have to reduce anything, as it is important to reduce physical activity and modify school workload while recovering but we should be avoiding the blanket recommendation to ‘stay home and do nothing until you are better’ approach to concussion management.”
Dr. Halstead and Dr. Moffatt reported no relevant financial conflicts to disclose; the same was true for the other report coauthors. There was no external funding for the report.
SOURCE: Halstead M et al. Pediatrics. 2018 Nov 12. doi: 10.1542/peds.2018-3074.
FROM PEDIATRICS
USPSTF advises primary care to screen for unhealthy alcohol use
All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.
Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.
However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.
Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.
After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.
Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.
In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.
In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.
None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.
The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.
The USPSTF recommendations to screen adults for unhealthy alcohol use acknowledge the serious public health problem it presents, wrote E. Jennifer Edelman, MD, and Jeanette M. Tetrault, MD, in an accompanying editorial.
The recommendations are similar to those issued in 2013 that endorsed screening and brief behavioral interventions for patients with at-risk alcohol use, they said. “Notably, the 2018 recommendations replace alcohol misuse with unhealthy alcohol use and explicitly recommend screening in all pregnant women,” they said.
In clinical practice, most patients with alcohol problems are seen for issues that are consequences of unhealthy alcohol use, such as poorly controlled hypertension, rather than the alcohol use itself, they noted. “Although patients are treated for their immediate problem, they often leave without clear plans to cut back or abstain from alcohol use and thus improve their health.”
Although the recommendations are based on studies showing the effectiveness of brief intervention in primary care, the interventions’ components tend not to be standardized in terms of content, delivery, dose, or duration, the editorialists noted. The terminology used in studies and in clinical practice is inconsistent as well and can cause confusion for doctors and stigma for patients, Dr. Edelman and Dr. Tetrault said.
In addition, they noted that the new USPSTF recommendations don’t incorporate guidance against any alcohol use while taking medications that may interact with it, such as sedating drugs and medications for opioid use disorders.
“Nonetheless, primary care physicians should focus on prevention of alcohol-related harms across the spectrum of alcohol use, including prescribing medications for alcohol use disorder when appropriate,” they noted. “Medications such as naltrexone, acamprosate, and disulfiram can easily be prescribed in primary care and do not require specific training” (JAMA. 2018 Nov 13. doi: 10.1001/jamainternmed.2018.6125).
Dr. Edelman and Dr. Tetrault are affiliated with Yale School of Medicine in New Haven, Conn. They had no financial conflicts to disclose.
The USPSTF recommendations to screen adults for unhealthy alcohol use acknowledge the serious public health problem it presents, wrote E. Jennifer Edelman, MD, and Jeanette M. Tetrault, MD, in an accompanying editorial.
The recommendations are similar to those issued in 2013 that endorsed screening and brief behavioral interventions for patients with at-risk alcohol use, they said. “Notably, the 2018 recommendations replace alcohol misuse with unhealthy alcohol use and explicitly recommend screening in all pregnant women,” they said.
In clinical practice, most patients with alcohol problems are seen for issues that are consequences of unhealthy alcohol use, such as poorly controlled hypertension, rather than the alcohol use itself, they noted. “Although patients are treated for their immediate problem, they often leave without clear plans to cut back or abstain from alcohol use and thus improve their health.”
Although the recommendations are based on studies showing the effectiveness of brief intervention in primary care, the interventions’ components tend not to be standardized in terms of content, delivery, dose, or duration, the editorialists noted. The terminology used in studies and in clinical practice is inconsistent as well and can cause confusion for doctors and stigma for patients, Dr. Edelman and Dr. Tetrault said.
In addition, they noted that the new USPSTF recommendations don’t incorporate guidance against any alcohol use while taking medications that may interact with it, such as sedating drugs and medications for opioid use disorders.
“Nonetheless, primary care physicians should focus on prevention of alcohol-related harms across the spectrum of alcohol use, including prescribing medications for alcohol use disorder when appropriate,” they noted. “Medications such as naltrexone, acamprosate, and disulfiram can easily be prescribed in primary care and do not require specific training” (JAMA. 2018 Nov 13. doi: 10.1001/jamainternmed.2018.6125).
Dr. Edelman and Dr. Tetrault are affiliated with Yale School of Medicine in New Haven, Conn. They had no financial conflicts to disclose.
The USPSTF recommendations to screen adults for unhealthy alcohol use acknowledge the serious public health problem it presents, wrote E. Jennifer Edelman, MD, and Jeanette M. Tetrault, MD, in an accompanying editorial.
The recommendations are similar to those issued in 2013 that endorsed screening and brief behavioral interventions for patients with at-risk alcohol use, they said. “Notably, the 2018 recommendations replace alcohol misuse with unhealthy alcohol use and explicitly recommend screening in all pregnant women,” they said.
In clinical practice, most patients with alcohol problems are seen for issues that are consequences of unhealthy alcohol use, such as poorly controlled hypertension, rather than the alcohol use itself, they noted. “Although patients are treated for their immediate problem, they often leave without clear plans to cut back or abstain from alcohol use and thus improve their health.”
Although the recommendations are based on studies showing the effectiveness of brief intervention in primary care, the interventions’ components tend not to be standardized in terms of content, delivery, dose, or duration, the editorialists noted. The terminology used in studies and in clinical practice is inconsistent as well and can cause confusion for doctors and stigma for patients, Dr. Edelman and Dr. Tetrault said.
In addition, they noted that the new USPSTF recommendations don’t incorporate guidance against any alcohol use while taking medications that may interact with it, such as sedating drugs and medications for opioid use disorders.
“Nonetheless, primary care physicians should focus on prevention of alcohol-related harms across the spectrum of alcohol use, including prescribing medications for alcohol use disorder when appropriate,” they noted. “Medications such as naltrexone, acamprosate, and disulfiram can easily be prescribed in primary care and do not require specific training” (JAMA. 2018 Nov 13. doi: 10.1001/jamainternmed.2018.6125).
Dr. Edelman and Dr. Tetrault are affiliated with Yale School of Medicine in New Haven, Conn. They had no financial conflicts to disclose.
All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.
Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.
However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.
Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.
After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.
Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.
In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.
In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.
None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.
The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.
All adults aged 18 years and older, including pregnant women, should be screened in primary care settings for unhealthy alcohol use and offered behavioral counseling if needed, according to recommendations from the U.S. Preventive Services Task Force.
Adults who meet the criteria for unhealthy alcohol use should be offered brief behavioral counseling interventions, the task force concluded with a B recommendation.
However, the task force also concluded that evidence is insufficient to recommend screening for alcohol use in adolescents aged 12-17 years in primary care settings (an I statement), wrote Susan J. Curry, PhD, of the University of Iowa, Iowa City, and colleagues. The recommendations were published in JAMA as an update of the USPSTF 2013 recommendation on screening for unhealthy alcohol use in primary care settings.
Approximately 88,000 deaths occurred each year in the United States between 2006 and 2010, the task force noted. Those deaths include death by acute causes, such as alcohol-related injuries, and chronic causes, such as alcoholic liver disease. In addition, alcohol use during pregnancy is a major preventable cause of birth defects and developmental disabilities, the task force wrote.
After reviewing the evidence, the USPSTF concluded that brief behavioral counseling offered moderate net benefits for adults 18 years and older, including pregnant women, who met criteria for unhealthy alcohol use.
Unhealthy alcohol used was defined as exceeding the National Institute on Alcohol Abuse and Alcoholism (NIAAA) recommended limits of 4 drinks per day, or 14 drinks per week, for men aged 21-64 years, and 3 drinks per day, or 7 drinks per week, for women aged 21-64 years.
In the evidence review accompanying the recommendations, Elizabeth A. O’Connor, PhD, of Kaiser Permanente in Portland, Ore., and colleagues analyzed data from 113 studies, including 314,466 individuals; 10 studies included adolescents.
In 68 studies including 36,528 individuals, brief counseling was associated with fewer drinks per week, fewer individuals exceeding recommended limits for alcohol consumption, fewer drinkers reporting a heavy drinking episode, and a greater proportion of pregnant women reporting alcohol abstinence after 6-12 months.
None of the studies assessed benefits or harms, but no evidence suggested that the interventions could be harmful.
The USPSTF is supported by the Agency for Healthcare Research and Quality. The researchers had no financial conflicts to disclose.
SOURCES: Curry S et al. JAMA. 2018;320(18):1899-1909; O’Connor E et al. JAMA. 2018;320(18):1910-28.
FROM JAMA
FDA accepts priority review of dupilumab for adolescent atopic dermatitis
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
The Food and Drug Administration has accepted the who have not been well controlled with topical therapies or who are unable to use topical therapies.
In a statement, dupilumab manufacturers Regeneron and Sanofi announced that the target action data for an FDA decision on dupilumab for adolescents is March 11, 2019. “Currently, there are no FDA-approved systemic biologic medicines to treat adolescents with moderate to severe atopic dermatitis,” the companies said in the statement.
The sBLA for dupilumab use in teens is based on data from a phase 3 study presented at the annual congress of European Academy of Dermatology and Venereology in September 2018. In that study, the proportion of patients who achieved a 75% or greater improvement in the Eczema Area and Severity Index at 16 weeks was 38.1% with monthly dupilumab, 41.5% with dupilumab every 2 weeks, and 8.2% with placebo.
According to the companies, the most common adverse events included injection site reactions, oropharyngeal pain, and cold sores. Conjunctivitis has also been reported in some patients.
Dupilumab (Dupixent), which inhibits interleukin-4 and interleukin-13 signaling, is currently approved for treating uncontrolled moderate to severe AD in adults and, more recently, as an add-on maintenance treatment in patients with moderate to severe asthma aged 12 years and older with an eosinophilic phenotype or with oral corticosteroid–dependent asthma.
The FDA granted Breakthrough Therapy designation for dupilumab in 2016 for the treatment of moderate to severe AD in adolescents and severe AD in children aged 6 months to 11 years who are insufficiently controlled with topical medications.
Guideline authors inconsistently disclose conflicts
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
None of the guidelines included in either study was fully compliant with National Academy of Medicine standards, which include written disclosure, appointing committee chairs or cochairs with no conflicts of interest, and keeping committee members with conflicts to a minority of the committee membership, wrote Colette DeJong, MD, and Robert Steinbrook, MD, in an accompanying editorial. In the study by Khan et al., “Notably, 14 of the 18 panels had chairs with industry payments, and 10 had a majority of members with payments,” they wrote.
However, the federal government has so far shown no interest in supporting a fully independent entity to develop clinical practice guidelines, as occurs in the United Kingdom via the National Institute for Health and Care Excellence. “Preparation of guidelines by an independent public body with assured funding and independence could be an effective approach, not only for eliminating issues related to financial conflicts of interest but also for assuring the use of rigorous methodologies and avoiding the wasteful duplication of efforts by multiple committees,” they wrote.
Financial conflicts in clinical practice guidelines persist in the United States in part because many professional societies have financial conflicts with industry, the editorialists wrote.
“Robust, objective, and unbiased clinical practice guidelines support improvements in patient care; the best interests of patients are the paramount consideration,” they emphasized (JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4974).
Dr. DeJong is affiliated with the University of California, San Francisco; Dr. Steinbrook is Editor at Large for JAMA Internal Medicine. They had no financial conflicts to disclose.
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
Financial conflicts are often underreported by authors of clinical practice guidelines (CPGs) in several specialties including oncology, rheumatology, and gastroenterology, according to a pair of research letters published in JAMA Internal Medicine. The Institute of Medicine recommends that guideline authors include no more than 50% individuals with financial conflicts.
In one research letter, Rishad Khan, BSc, of the University of Toronto in Ontario and his colleagues reviewed data on undeclared financial conflicts of interest among authors of guidelines related to high-revenue medications.
The researchers identified CPGs via the National Guideline Clearinghouse and selected 18 CPGs for 10 high-revenue medications published between 2013 and 2017. Financial conflicts of interest were based on the Centers for Medicare & Medicaid Services Open Payments.
Of the 160 authors involved in the various guidelines, 79 (49.4%) disclosed a payment in the CPG or supplemental materials, and 50 (31.3%) disclosed payments from companies marketing 1 of the 10 high-revenue medications in the related guidelines.
Another 41 authors (25.6%) received but did not disclose payments from companies marketing 1 of the 10 high-revenue medications in CPGs.
Overall, 91 authors (56.9%) were found to have financial conflicts of interest that involved 1 of the 10 high-revenue medications, and “the median value of undeclared payments from companies marketing 1 of the 10 high-revenue medications recommended in the CPGs was $522 (interquartile range, $0-$40,444) from two companies,” the researchers said.
The study findings were limited by several factors including “potential inaccuracies in CMS-OP reporting, which are rarely corrected, and lack of generalizability outside the United States” and by the limited time frame for data collection, which may have led to underestimation of conflicts for the guidelines, the researchers noted. In addition, “we did not have access to guideline voting records and thus did not know when conflicted panel members recommended against a medication or recused themselves from voting,” they said.
Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals.
In a second research letter, half of the authors of gastroenterology guidelines received payments from industry, wrote Tyler Combs, BS, of Oklahoma State University, Tulsa, and his colleagues. Previous studies have reviewed the financial conflicts of interest in specialties including oncology, dermatology, and otolaryngology, but financial conflicts of interest among authors of gastroenterology guidelines have not been examined, the researchers said.
Mr. Combs and his colleagues identified 15 CPGs published by the American College of Gastroenterology between 2014 and 2016. They identified 83 authors, with an average of 4 authors for each guideline. Overall, 53% of the authors received industry payments, according to based on data from the 2014 to 2016 Centers for Medicare and Medicaid Services Open Payments database (OPD).
However, OPD information was not always consistent with information published with the guidelines, the researchers noted. They found that 16 (19%) of the 83 authors both disclosed financial conflicts of interests in the CPGs and had received payments according to OPD or had disclosed no financial conflicts of interest and had received no payments according to OPD. In addition, 49 (34%) of 146 cumulative financial conflicts of interest disclosed in the CPGs and 148 relationships identified on OPD were both disclosed as financial conflicts of interest and evidenced by OPD payment records. In this review, the median total payment was $1,000, with an interquartile range from $0 to $39,938.
The study findings were limited by a relatively short 12-month time frame, the researchers noted. However, “our finding that FCOI [financial conflicts of interest] disclosure only corroborates with OPD payment records between 19% and 34% of the time also suggests that guidance from the ACG [American College of Gastroenterology] may be needed to improve FCOI disclosure efforts in future iterations of gastroenterology CPGs,” they said.
The researchers had no financial conflicts to disclose.
SOURCE: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Financial conflicts of interest in the development of clinical guidelines persist in the United States.
Major finding: Approximately half of the committee members of guidelines in both studies had financial relationships; many were undisclosed and involved substantial payments.
Study details: The data come from two research letters, including 15 gastroenterology guidelines and 18 guidelines from multiple specialties.
Disclosures: Mr. Khan disclosed research funding from AbbVie and Ferring Pharmaceuticals. Mr. Combs had no financial conflicts to disclose.
Source: Combs T et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.4730. Khan R et al. JAMA Intern Med. 2018 Oct 29. doi: 10.1001/jamainternmed.2018.5106.
FDA panels back brexanolone infusion for postpartum depression
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 2 in support of brexanolone infusion as a treatment for postpartum depression.
The 17-1 vote by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based primarily on data from three studies, including 247 women aged 18-44 years with postpartum depression; 140 received brexanolone and 107 received placebo. Effectiveness was assessed based on the Hamilton Depression Scale (HAM-D) at the end of the infusion (hour 60).
In all three studies, patients given brexanolone showed significantly improved HAM-D scores, compared with placebo. The patients experienced significant differences at hour 24, which illustrated the rapid response. “The individual item scores of the HAM-D consistently favored brexanolone IV over placebo, confirming an overall antidepressant effect of the drug,” according to the briefing document of Sage Therapeutics, developer of the drug. In addition, more than 80% of the patients in the treatment and placebo groups sustained their improvement in symptoms at 30 days after the end of the infusion.
“[Postpartum depression] is symptomatically indistinguishable from an episode of major depression,” the FDA briefing document said. “However, the timing of its onset has led to its recognition as a potentially unique illness. There are no drugs specifically approved to treat [postpartum depression].”
Some clinicians use drugs approved for major depression to treat postpartum depression, but the effectiveness of these drugs is limited, the agency said. Other interventions, such as electroconvulsive therapy, repetitive transcranial magnetic stimulation, and psychotherapy also are used, but they can take several weeks to show results.
Recent estimates of postpartum depression in the United States range from about 8% to 20%, according to the FDA document. and both the FDA and Sage Therapeutics agreed on the need for additional treatment options for women with postpartum depression. , according to Sage.
The treatment protocol for brexanolone involves a single 60-hour continuous infusion with a recommended maximum dose of 90 µg/kg/h, referred to as a “90 dose regimen.” The patient receives a single infusion per episode of postpartum depression. The infusion includes three dosing phases: titration at 30 μg/kg/h for 4 hours followed by 60 μg/kg/h for 20 hours (hour 0-24), maintenance at 90 μg/kg/h for 28 hours (hour 24-52), and taper at 60 μg/kg/h for 4 hours – followed by 30 μg/kg/h for 4 hours (hour 52-60).
Brexanolone is an allosteric modulator of GABAA receptors and “a new molecular entity not currently marketed anywhere in the world for any indication,” according to the FDA document. The drug originally was studied as a treatment for seizure patients before its antidepressant properties were discovered.
Adverse reactions observed in 3% or more of the brexanolone patients during the 60-hour treatment and 4-week follow-up included dry mouth, infusion site pain, fatigue, headache, sedation/somnolence, dizziness/vertigo, and loss of consciousness.
Of those reactions, loss of consciousness was the issue of greatest concern to the committee members and informed their discussion of the strict Risk Evaluation and Mitigation Strategy protocol that would be needed to accompany approval of the drug. The details of the REMS will be determined, but the basics of the FDA’s proposed REMS to mitigate the risk of loss of consciousness include administration of the drug only in medically supervised settings by an authorized representative.
In addition, the proposed REMS states that the authorized representative must “establish policies and procedures to ensure that 1) all staff are trained on the risks and 2) the product is not dispensed for use outside the health care setting.”
The proposed REMS also stated that, “Patients must be continuously monitored for the duration of the infusion and 12 hours after, by health care provider who can intervene if the patient experiences excessive sedation or loss of consciousness.”
Despite those concerns, which most committee members thought could be addressed by the REMS, the overall impression of the committees’ members was that brexanolone could have a significant impact on postpartum depression. According to one member, brexanolone is mechanistically “groundbreaking” and “could be a tremendous help in changing the trajectory of postpartum depression.”
The FDA usually follows its panels’ recommendations, which are not binding.
Pediatric indications appear in one-third of orphan drug approvals
WASHINGTON – Pediatric indications appeared in approximately 36% of orphan drug approvals between 2000 and 2017, according to data from the Food and Drug Administration.
“Given the impact of rare disease on children, it is of particular interest to better understand where new drug approvals and advances are occurring, through the lens of pediatrics,” said Kathleen L. Miller, Ph.D., and Michael Lanthier of the Food and Drug Administration in Silver Spring, Md. They presented their findings in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
Overall, 31% of 314 orphan drug approvals by the FDA between 2000 and 2017 had a pediatric and adult indication, 5% had pediatric-only indications, and 64% had adult-only indications.
For the 112 pediatric indication approvals, 14% were for inherited blood disorders, 14% for inherited metabolic disorders, 13% for rare cancers, 10% for antidotes and medical countermeasures, 9% for infectious diseases, 8% for auto-inflammatory diseases, 7% for neurologic disorders, and 25% for other conditions.
Approximately 63% of the total orphan drug approvals during the study period were for rare cancers or genetic disorders (138 approvals and 59 approvals, respectively). Although 90% of the rare cancer approvals were for adults only, 84% of genetic disorder drug approvals had pediatric indications, Dr. Miller and Mr. Lanthier noted.
When analyzed by submission type, pediatric indications were included in 52% of new orphan formulations, 35% of orphan secondary indication approvals, and 32% of new molecular entity approvals.
Although more research is needed, the results suggest that “pediatric indications represent a sizable proportion of orphan drug approvals in both a range of therapeutic areas and in a range of approval types,” the investigators concluded.
The researchers are employed by the FDA, which sponsored the study. They had no financial conflicts to disclose.
WASHINGTON – Pediatric indications appeared in approximately 36% of orphan drug approvals between 2000 and 2017, according to data from the Food and Drug Administration.
“Given the impact of rare disease on children, it is of particular interest to better understand where new drug approvals and advances are occurring, through the lens of pediatrics,” said Kathleen L. Miller, Ph.D., and Michael Lanthier of the Food and Drug Administration in Silver Spring, Md. They presented their findings in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
Overall, 31% of 314 orphan drug approvals by the FDA between 2000 and 2017 had a pediatric and adult indication, 5% had pediatric-only indications, and 64% had adult-only indications.
For the 112 pediatric indication approvals, 14% were for inherited blood disorders, 14% for inherited metabolic disorders, 13% for rare cancers, 10% for antidotes and medical countermeasures, 9% for infectious diseases, 8% for auto-inflammatory diseases, 7% for neurologic disorders, and 25% for other conditions.
Approximately 63% of the total orphan drug approvals during the study period were for rare cancers or genetic disorders (138 approvals and 59 approvals, respectively). Although 90% of the rare cancer approvals were for adults only, 84% of genetic disorder drug approvals had pediatric indications, Dr. Miller and Mr. Lanthier noted.
When analyzed by submission type, pediatric indications were included in 52% of new orphan formulations, 35% of orphan secondary indication approvals, and 32% of new molecular entity approvals.
Although more research is needed, the results suggest that “pediatric indications represent a sizable proportion of orphan drug approvals in both a range of therapeutic areas and in a range of approval types,” the investigators concluded.
The researchers are employed by the FDA, which sponsored the study. They had no financial conflicts to disclose.
WASHINGTON – Pediatric indications appeared in approximately 36% of orphan drug approvals between 2000 and 2017, according to data from the Food and Drug Administration.
“Given the impact of rare disease on children, it is of particular interest to better understand where new drug approvals and advances are occurring, through the lens of pediatrics,” said Kathleen L. Miller, Ph.D., and Michael Lanthier of the Food and Drug Administration in Silver Spring, Md. They presented their findings in a poster at the NORD Rare Summit, held by the National Organization for Rare Disorders.
Overall, 31% of 314 orphan drug approvals by the FDA between 2000 and 2017 had a pediatric and adult indication, 5% had pediatric-only indications, and 64% had adult-only indications.
For the 112 pediatric indication approvals, 14% were for inherited blood disorders, 14% for inherited metabolic disorders, 13% for rare cancers, 10% for antidotes and medical countermeasures, 9% for infectious diseases, 8% for auto-inflammatory diseases, 7% for neurologic disorders, and 25% for other conditions.
Approximately 63% of the total orphan drug approvals during the study period were for rare cancers or genetic disorders (138 approvals and 59 approvals, respectively). Although 90% of the rare cancer approvals were for adults only, 84% of genetic disorder drug approvals had pediatric indications, Dr. Miller and Mr. Lanthier noted.
When analyzed by submission type, pediatric indications were included in 52% of new orphan formulations, 35% of orphan secondary indication approvals, and 32% of new molecular entity approvals.
Although more research is needed, the results suggest that “pediatric indications represent a sizable proportion of orphan drug approvals in both a range of therapeutic areas and in a range of approval types,” the investigators concluded.
The researchers are employed by the FDA, which sponsored the study. They had no financial conflicts to disclose.
REPORTING FROM NORD SUMMIT 2018
Key clinical point:
Major finding: A total of 112 orphan drug approvals between 2000 and 2017 included a pediatric indication.
Study details: The data come from a review of 314 orphan drug approvals by the FDA between 2000 and 2017.
Disclosures: The researchers are employed by the Food and Drug Administration, which sponsored the study. They had no financial conflicts to disclose.
FDA panels vote no on opioid-containing drug for MDD
A joint panel of the Food and Drug Administration voted Nov. 1 against approving a new opioid-containing drug as an adjunctive treatment for major depressive disorder.
The 21-2 vote against approval by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based on concerns that the drug’s benefit-risk profile was not strong enough to warrant approval, according to a press release from Alkermes, developer of the drug, which is a combination of buprenorphine and samidorphan known as ALKS 5461.
“We were disappointed and surprised by the FDA’s characterization of the safety and efficacy data for ALKS 5461 and the resulting outcome of the advisory committee vote, particularly for the patients, their families and treatment providers who need and deserve access to novel therapies that work differently than currently available antidepressants, Richard Pops, chief executive officer of Alkermes, said in the release. “We remain steadfast in our commitment to make a meaningful difference in the lives of people suffering with serious mental health conditions, and will continue to work with the FDA as it completes its review of the ALKS 5461 regulatory submission.”
At the meeting, Sanjay J. Mathew, MD, a psychiatrist affiliated with the Baylor College of Medicine in Houston and a consultant for Alkermes who was paid for his time and travel to the meeting, discussed which patients might be good candidates for the new drug. He used an example of a patient who had failed on several monotherapies and would consider augmentation with a second drug. “In my view, this drug has a positive benefit-risk profile with a comparable efficacy” to currently available drugs, but with a new distinct mechanism that appears not to have certain undesirable side effects such as weight gain and sleepiness, he said.
Meanwhile, representatives from Alkermes discussed phase 3 studies, in which adults with treatment-resistant major depressive disorder were randomized to BUP/SAM in doses of 1mg/1mg or 2mg/2mg, or a placebo. In the trial, known as Study 207, changes in the MADRAS-10 total scores were significantly higher in the 2mg/2mg treatment groups, compared with placebo when data from 5 weeks and 6 weeks of treatment were combined.
However, in the FDA’s review of the data, it was noted that the efficacy was based on the MADRAS-10 average vs. the MADRAS-10 end of treatment, and the average “tends to obscure a possible drop-off in drug efficacy after the first few weeks of treatment.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 1 against approving a new opioid-containing drug as an adjunctive treatment for major depressive disorder.
The 21-2 vote against approval by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based on concerns that the drug’s benefit-risk profile was not strong enough to warrant approval, according to a press release from Alkermes, developer of the drug, which is a combination of buprenorphine and samidorphan known as ALKS 5461.
“We were disappointed and surprised by the FDA’s characterization of the safety and efficacy data for ALKS 5461 and the resulting outcome of the advisory committee vote, particularly for the patients, their families and treatment providers who need and deserve access to novel therapies that work differently than currently available antidepressants, Richard Pops, chief executive officer of Alkermes, said in the release. “We remain steadfast in our commitment to make a meaningful difference in the lives of people suffering with serious mental health conditions, and will continue to work with the FDA as it completes its review of the ALKS 5461 regulatory submission.”
At the meeting, Sanjay J. Mathew, MD, a psychiatrist affiliated with the Baylor College of Medicine in Houston and a consultant for Alkermes who was paid for his time and travel to the meeting, discussed which patients might be good candidates for the new drug. He used an example of a patient who had failed on several monotherapies and would consider augmentation with a second drug. “In my view, this drug has a positive benefit-risk profile with a comparable efficacy” to currently available drugs, but with a new distinct mechanism that appears not to have certain undesirable side effects such as weight gain and sleepiness, he said.
Meanwhile, representatives from Alkermes discussed phase 3 studies, in which adults with treatment-resistant major depressive disorder were randomized to BUP/SAM in doses of 1mg/1mg or 2mg/2mg, or a placebo. In the trial, known as Study 207, changes in the MADRAS-10 total scores were significantly higher in the 2mg/2mg treatment groups, compared with placebo when data from 5 weeks and 6 weeks of treatment were combined.
However, in the FDA’s review of the data, it was noted that the efficacy was based on the MADRAS-10 average vs. the MADRAS-10 end of treatment, and the average “tends to obscure a possible drop-off in drug efficacy after the first few weeks of treatment.”
The FDA usually follows its panels’ recommendations, which are not binding.
A joint panel of the Food and Drug Administration voted Nov. 1 against approving a new opioid-containing drug as an adjunctive treatment for major depressive disorder.
The 21-2 vote against approval by members of the Psychopharmacologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee was based on concerns that the drug’s benefit-risk profile was not strong enough to warrant approval, according to a press release from Alkermes, developer of the drug, which is a combination of buprenorphine and samidorphan known as ALKS 5461.
“We were disappointed and surprised by the FDA’s characterization of the safety and efficacy data for ALKS 5461 and the resulting outcome of the advisory committee vote, particularly for the patients, their families and treatment providers who need and deserve access to novel therapies that work differently than currently available antidepressants, Richard Pops, chief executive officer of Alkermes, said in the release. “We remain steadfast in our commitment to make a meaningful difference in the lives of people suffering with serious mental health conditions, and will continue to work with the FDA as it completes its review of the ALKS 5461 regulatory submission.”
At the meeting, Sanjay J. Mathew, MD, a psychiatrist affiliated with the Baylor College of Medicine in Houston and a consultant for Alkermes who was paid for his time and travel to the meeting, discussed which patients might be good candidates for the new drug. He used an example of a patient who had failed on several monotherapies and would consider augmentation with a second drug. “In my view, this drug has a positive benefit-risk profile with a comparable efficacy” to currently available drugs, but with a new distinct mechanism that appears not to have certain undesirable side effects such as weight gain and sleepiness, he said.
Meanwhile, representatives from Alkermes discussed phase 3 studies, in which adults with treatment-resistant major depressive disorder were randomized to BUP/SAM in doses of 1mg/1mg or 2mg/2mg, or a placebo. In the trial, known as Study 207, changes in the MADRAS-10 total scores were significantly higher in the 2mg/2mg treatment groups, compared with placebo when data from 5 weeks and 6 weeks of treatment were combined.
However, in the FDA’s review of the data, it was noted that the efficacy was based on the MADRAS-10 average vs. the MADRAS-10 end of treatment, and the average “tends to obscure a possible drop-off in drug efficacy after the first few weeks of treatment.”
The FDA usually follows its panels’ recommendations, which are not binding.
Medical exemptions spike after vaccine policy change
according to data from interviews with health officials and immunization staff after implementation of the policy.
In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.
Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.
They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.
Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.
“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.
“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.
Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.
Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.
There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.
The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.
The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.
SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.
Passage of SB277 has had a positive impact on the proportion of California kindergarteners who are fully vaccinated, Richard J. Pan, MD, MPH, and Dorit Rubinstein Reiss, LLB, PhD, wrote in an editorial.
“Vaccines are one of the greatest public health successes in history. Mandating vaccination for school is an effective strategy to prevent outbreaks,” they said. However, “this protection is undermined when unscrupulous physicians monetize their license and abuse the authority delegated to them from the state by granting unwarranted [medical exemptions (MEs)],” they said.
The editorialists emphasized that states have the authority to mandate vaccinations in the interest of public health, and that allowing physicians to grant medical exemptions is appropriate because doctors know their patients and know whether exemptions are needed.
“However, the lack of cooperation by patients’ families who desire unwarranted MEs makes disciplining physicians who are engaged in this unprofessional behavior difficult and costly because licensing boards need to subpoena patient records over families’ objections to obtain evidence. Similarly, professional standard-setting organizations, including professional associations and certification boards, have been reluctant to withdraw credentials or expel members who promote vaccine misinformation and grant unwarranted MEs,” they said. They proposed strategies including establishing a searchable database for MEs, allowing public health officials the option to review and invalidate MEs, and requiring parents to submit MEs to public health departments as well as to schools.
“Pediatricians can partner with public health advocates and proscience parents to pass laws that empower public health officers to protect our children and community. Every child needs community immunity,” they said.
Dr. Pan is a California State Senator, Sacramento, and Dr. Reiss is at the Hastings College of the Law, University of California, San Francisco. Their comments on the article by Mohanty et al. were published in Pediatrics (2018;142[5]:e20182009). Dr. Pan authored legislation (Senate Bill 277) to abolish nonmedical exemption. Dr. Reiss’s family owns regular stock in GlaxoSmithKline.
Passage of SB277 has had a positive impact on the proportion of California kindergarteners who are fully vaccinated, Richard J. Pan, MD, MPH, and Dorit Rubinstein Reiss, LLB, PhD, wrote in an editorial.
“Vaccines are one of the greatest public health successes in history. Mandating vaccination for school is an effective strategy to prevent outbreaks,” they said. However, “this protection is undermined when unscrupulous physicians monetize their license and abuse the authority delegated to them from the state by granting unwarranted [medical exemptions (MEs)],” they said.
The editorialists emphasized that states have the authority to mandate vaccinations in the interest of public health, and that allowing physicians to grant medical exemptions is appropriate because doctors know their patients and know whether exemptions are needed.
“However, the lack of cooperation by patients’ families who desire unwarranted MEs makes disciplining physicians who are engaged in this unprofessional behavior difficult and costly because licensing boards need to subpoena patient records over families’ objections to obtain evidence. Similarly, professional standard-setting organizations, including professional associations and certification boards, have been reluctant to withdraw credentials or expel members who promote vaccine misinformation and grant unwarranted MEs,” they said. They proposed strategies including establishing a searchable database for MEs, allowing public health officials the option to review and invalidate MEs, and requiring parents to submit MEs to public health departments as well as to schools.
“Pediatricians can partner with public health advocates and proscience parents to pass laws that empower public health officers to protect our children and community. Every child needs community immunity,” they said.
Dr. Pan is a California State Senator, Sacramento, and Dr. Reiss is at the Hastings College of the Law, University of California, San Francisco. Their comments on the article by Mohanty et al. were published in Pediatrics (2018;142[5]:e20182009). Dr. Pan authored legislation (Senate Bill 277) to abolish nonmedical exemption. Dr. Reiss’s family owns regular stock in GlaxoSmithKline.
Passage of SB277 has had a positive impact on the proportion of California kindergarteners who are fully vaccinated, Richard J. Pan, MD, MPH, and Dorit Rubinstein Reiss, LLB, PhD, wrote in an editorial.
“Vaccines are one of the greatest public health successes in history. Mandating vaccination for school is an effective strategy to prevent outbreaks,” they said. However, “this protection is undermined when unscrupulous physicians monetize their license and abuse the authority delegated to them from the state by granting unwarranted [medical exemptions (MEs)],” they said.
The editorialists emphasized that states have the authority to mandate vaccinations in the interest of public health, and that allowing physicians to grant medical exemptions is appropriate because doctors know their patients and know whether exemptions are needed.
“However, the lack of cooperation by patients’ families who desire unwarranted MEs makes disciplining physicians who are engaged in this unprofessional behavior difficult and costly because licensing boards need to subpoena patient records over families’ objections to obtain evidence. Similarly, professional standard-setting organizations, including professional associations and certification boards, have been reluctant to withdraw credentials or expel members who promote vaccine misinformation and grant unwarranted MEs,” they said. They proposed strategies including establishing a searchable database for MEs, allowing public health officials the option to review and invalidate MEs, and requiring parents to submit MEs to public health departments as well as to schools.
“Pediatricians can partner with public health advocates and proscience parents to pass laws that empower public health officers to protect our children and community. Every child needs community immunity,” they said.
Dr. Pan is a California State Senator, Sacramento, and Dr. Reiss is at the Hastings College of the Law, University of California, San Francisco. Their comments on the article by Mohanty et al. were published in Pediatrics (2018;142[5]:e20182009). Dr. Pan authored legislation (Senate Bill 277) to abolish nonmedical exemption. Dr. Reiss’s family owns regular stock in GlaxoSmithKline.
according to data from interviews with health officials and immunization staff after implementation of the policy.
In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.
Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.
They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.
Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.
“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.
“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.
Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.
Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.
There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.
The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.
The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.
SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.
according to data from interviews with health officials and immunization staff after implementation of the policy.
In a study published in Pediatrics, Salini Mohanty, DrPH, of the University of Pennsylvania School of Nursing, Philadelphia, and her colleagues conducted semistructured phone interviews with 40 health officers and immunization staff who represented 35 of 61 California heath jurisdictions. The interviews occurred between August 2017 and September 2017, and participants discussed their experiences with medical exemption requests after the policy change.
Although the percentage of fully vaccinated kindergarten students in California increased from 93% in 2015-2016 to 95% in 2017-2018, and the rate of personal belief exemptions declined, overall medical exemption requests rose 250% from 0.2% in 2015-2016 to 0.7% 2017-2018, the researchers noted.
They identified four main issues based on participant responses: the role of stakeholders, the review of medical exemptions received by schools, the medical exemptions perceived as problematic, and the general frustration and concern over medical exemptions.
Based on the interviews, one concerning subtheme involved reports that some physicians wrote medical exemptions for vaccine-hesitant parents based on conditions such as allergies and autoimmune diseases.
“The Internet provides access to physicians who are willing to sign off on exemptions and to websites used to instruct parents on how to get physicians to approve medical exemptions,” the researchers said.
“Understanding how physicians interpret the law is important because they are writing the medical exemptions,” Dr. Mohanty and her associates noted, and they proposed increased outreach and education of physicians about the law to reduce problematic medical exemptions.
Many health officials expressed frustration with their inability to review medical exemptions submitted directly to schools. In fact, interviewees cited one California jurisdiction that was named in a lawsuit for attempting to track medical exemptions, “which had an impact on other jurisdictions decision to track,” they said.
Officials also expressed concern that parents’ use of medical exemptions to replace personal belief exemptions would reduce herd immunity. Overall, regions with high levels of personal belief exemptions showed the largest increases in medical exemptions after SB277, which could put these regions at increased risk for vaccine-preventable outbreaks, the researchers noted.
There also were reports of physicians “who advertised medical exemptions online for a fee.” Officials also reported “receiving medical exemptions signed by physicians who do not typically treat children (cardiologists, dermatologists, surgeons, and physicians at medical marijuana dispensaries) and by unauthorized nonphysician providers, including nurse practitioners,” Dr. Mohanty and her associates said.
The study findings were limited by several factors including small sample size and potential recall bias, the researchers noted. However, the study is the first to include perspectives of local health officials after a change in vaccine exemption policy.
The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.
SOURCE: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.
FROM PEDIATRICS
Key clinical point: Medical exemptions for childhood vaccinations in California increased after the implementation of Senate Bill 277 (SB277) eliminating nonmedical exemptions.
Major finding: Medical exemptions in California increased by 250% after the SB277 took effect.
Study details: The data come from 34 interviews with 40 health officers and immunization staff about their experiences with medical exemptions before and after the passage of SB277.
Disclosures: The National Institutes of Health supported the study. Dr. Mohanty had no financial conflicts to disclose; one coauthor disclosed relationships with Merck, Pfizer, and Walgreens.
Source: Mohanty S et al. Pediatrics. 2018. doi: 10.1542/peds.2018-1051.
Full-dose quadrivalent flu vaccine shows increased efficacy in children
according to data from a randomized trial of nearly 2,000 children aged 6-35 months.
Data from previous studies have suggested that a full dose of vaccine may be more immunogenic in young children compared with a half dose, and Sanofi Pasteur has submitted a supplemental Biologics License Application to the Food and Drug Administration to allow use of the full 0.5-mL dose in children as young as 6 months, Monica Mercer, MD, of Sanofi Pasteur, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
Dr. Mercer presented findings from a phase IV randomized, observer-blinded study, in which the researchers assigned healthy children aged 6-35 months to receive Fluzone quadrivalent vaccine at a dose of 0.25 mL or 0.5 mL.
A total of 1,941 children (949 for the 0.25-mL dose and 992 for the 0.5-mL dose) were included in the safety analysis.
The most important safety outcome was to compare the rate of any fever, Dr. Mercer said at the meeting.
Overall, at 7 days after vaccination, the rate of fever was 11% for the half dose and 12% for the full dose, she said. The resulting difference of 0.84% met the criteria for noninferiority (less than 5%), she added.
In terms of safety, tenderness was the most frequently reported injection site reaction, noted in 47% of the half-dose group and 50% of the full-dose group. The rates of unsolicited adverse events were similar in both groups, the most common included diarrhea and cough, Dr. Mercer said.
No subjects in the full-dose group and three in the half-dose group discontinued the study because of adverse events. The only reported serious adverse event was one case of chronic urticaria in the half-dose group; no deaths were reported in either group.
As for efficacy, the full dose demonstrated noninferiority, compared with the half dose, against each of four strains: influenza A H1N1, influenza A H3N2, influenza B Victoria, and influenza B Yamagata. The geometric mean titers of the full and half doses for each of the four strains were, respectively, 310 and 214, 332 and 221, 348 and 261, and 349 and 243.
The potential action date for the supplemental Biologics License Application is January 2019, noted Dr. Mercer, who is employed by Sanofi Pasteur.
according to data from a randomized trial of nearly 2,000 children aged 6-35 months.
Data from previous studies have suggested that a full dose of vaccine may be more immunogenic in young children compared with a half dose, and Sanofi Pasteur has submitted a supplemental Biologics License Application to the Food and Drug Administration to allow use of the full 0.5-mL dose in children as young as 6 months, Monica Mercer, MD, of Sanofi Pasteur, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
Dr. Mercer presented findings from a phase IV randomized, observer-blinded study, in which the researchers assigned healthy children aged 6-35 months to receive Fluzone quadrivalent vaccine at a dose of 0.25 mL or 0.5 mL.
A total of 1,941 children (949 for the 0.25-mL dose and 992 for the 0.5-mL dose) were included in the safety analysis.
The most important safety outcome was to compare the rate of any fever, Dr. Mercer said at the meeting.
Overall, at 7 days after vaccination, the rate of fever was 11% for the half dose and 12% for the full dose, she said. The resulting difference of 0.84% met the criteria for noninferiority (less than 5%), she added.
In terms of safety, tenderness was the most frequently reported injection site reaction, noted in 47% of the half-dose group and 50% of the full-dose group. The rates of unsolicited adverse events were similar in both groups, the most common included diarrhea and cough, Dr. Mercer said.
No subjects in the full-dose group and three in the half-dose group discontinued the study because of adverse events. The only reported serious adverse event was one case of chronic urticaria in the half-dose group; no deaths were reported in either group.
As for efficacy, the full dose demonstrated noninferiority, compared with the half dose, against each of four strains: influenza A H1N1, influenza A H3N2, influenza B Victoria, and influenza B Yamagata. The geometric mean titers of the full and half doses for each of the four strains were, respectively, 310 and 214, 332 and 221, 348 and 261, and 349 and 243.
The potential action date for the supplemental Biologics License Application is January 2019, noted Dr. Mercer, who is employed by Sanofi Pasteur.
according to data from a randomized trial of nearly 2,000 children aged 6-35 months.
Data from previous studies have suggested that a full dose of vaccine may be more immunogenic in young children compared with a half dose, and Sanofi Pasteur has submitted a supplemental Biologics License Application to the Food and Drug Administration to allow use of the full 0.5-mL dose in children as young as 6 months, Monica Mercer, MD, of Sanofi Pasteur, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
Dr. Mercer presented findings from a phase IV randomized, observer-blinded study, in which the researchers assigned healthy children aged 6-35 months to receive Fluzone quadrivalent vaccine at a dose of 0.25 mL or 0.5 mL.
A total of 1,941 children (949 for the 0.25-mL dose and 992 for the 0.5-mL dose) were included in the safety analysis.
The most important safety outcome was to compare the rate of any fever, Dr. Mercer said at the meeting.
Overall, at 7 days after vaccination, the rate of fever was 11% for the half dose and 12% for the full dose, she said. The resulting difference of 0.84% met the criteria for noninferiority (less than 5%), she added.
In terms of safety, tenderness was the most frequently reported injection site reaction, noted in 47% of the half-dose group and 50% of the full-dose group. The rates of unsolicited adverse events were similar in both groups, the most common included diarrhea and cough, Dr. Mercer said.
No subjects in the full-dose group and three in the half-dose group discontinued the study because of adverse events. The only reported serious adverse event was one case of chronic urticaria in the half-dose group; no deaths were reported in either group.
As for efficacy, the full dose demonstrated noninferiority, compared with the half dose, against each of four strains: influenza A H1N1, influenza A H3N2, influenza B Victoria, and influenza B Yamagata. The geometric mean titers of the full and half doses for each of the four strains were, respectively, 310 and 214, 332 and 221, 348 and 261, and 349 and 243.
The potential action date for the supplemental Biologics License Application is January 2019, noted Dr. Mercer, who is employed by Sanofi Pasteur.
REPORTING FROM AN ACIP MEETING
Vaccine protects against flu-related hospitalizations in pregnancy
A review of more than 1,000 hospitalizations revealed a 40% influenza vaccine effectiveness against laboratory-confirmed influenza-associated hospitalizations during pregnancy, Mark Thompson, MD, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
To date, no study has examined influenza vaccine effectiveness (IVE) against hospitalizations among pregnant women, said Dr. Thompson, of the CDC’s influenza division.
He presented results of a study based on data from the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), which included public health or health care systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and three states (California, Oregon, and Washington). The study included women aged 18-50 years who were pregnant during local influenza seasons from 2010 to 2016. Most of the women were older than 35 years (79%), and in the third trimester (65%), and had no high risk medical conditions (66%). The study was published in Clinical Infectious Diseases (2018 Oct 11. doi: 10.1093/cid/ciy737).
The researchers identified 19,450 hospitalizations with an acute respiratory or febrile illness discharge diagnosis and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for flu viruses. Of these, 1,030 (6%) of the women underwent rRT-PCR testing, 54% were diagnosed with either influenza or pneumonia, and 58% had detectable influenza A or B virus infections.
Overall, the adjusted IVE was 40%; 13% of rRT-PCR-confirmed influenza-positive pregnant women and 22% of influenza-negative pregnant women were vaccinated; IVE was adjusted for site, season, season timing, and high-risk medical conditions.
“The takeaway is this is the average performance of the vaccine across multiple countries and different seasons,” and the vaccine effectiveness appeared stable across high-risk medical conditions and trimesters of pregnancy, Dr. Thompson said.
The generalizability of the study findings was limited by the lack of data from low- to middle-income countries, he said during the meeting discussion. However, the ICU admission rate is “what we would expect” and similar to results from previous studies. The consistent results showed the need to increase flu vaccination for pregnant women worldwide and to include study populations from lower-income countries in future research.
Dr. Thompson had no financial conflicts to disclose.
A review of more than 1,000 hospitalizations revealed a 40% influenza vaccine effectiveness against laboratory-confirmed influenza-associated hospitalizations during pregnancy, Mark Thompson, MD, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
To date, no study has examined influenza vaccine effectiveness (IVE) against hospitalizations among pregnant women, said Dr. Thompson, of the CDC’s influenza division.
He presented results of a study based on data from the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), which included public health or health care systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and three states (California, Oregon, and Washington). The study included women aged 18-50 years who were pregnant during local influenza seasons from 2010 to 2016. Most of the women were older than 35 years (79%), and in the third trimester (65%), and had no high risk medical conditions (66%). The study was published in Clinical Infectious Diseases (2018 Oct 11. doi: 10.1093/cid/ciy737).
The researchers identified 19,450 hospitalizations with an acute respiratory or febrile illness discharge diagnosis and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for flu viruses. Of these, 1,030 (6%) of the women underwent rRT-PCR testing, 54% were diagnosed with either influenza or pneumonia, and 58% had detectable influenza A or B virus infections.
Overall, the adjusted IVE was 40%; 13% of rRT-PCR-confirmed influenza-positive pregnant women and 22% of influenza-negative pregnant women were vaccinated; IVE was adjusted for site, season, season timing, and high-risk medical conditions.
“The takeaway is this is the average performance of the vaccine across multiple countries and different seasons,” and the vaccine effectiveness appeared stable across high-risk medical conditions and trimesters of pregnancy, Dr. Thompson said.
The generalizability of the study findings was limited by the lack of data from low- to middle-income countries, he said during the meeting discussion. However, the ICU admission rate is “what we would expect” and similar to results from previous studies. The consistent results showed the need to increase flu vaccination for pregnant women worldwide and to include study populations from lower-income countries in future research.
Dr. Thompson had no financial conflicts to disclose.
A review of more than 1,000 hospitalizations revealed a 40% influenza vaccine effectiveness against laboratory-confirmed influenza-associated hospitalizations during pregnancy, Mark Thompson, MD, said at a meeting of the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices in Atlanta.
To date, no study has examined influenza vaccine effectiveness (IVE) against hospitalizations among pregnant women, said Dr. Thompson, of the CDC’s influenza division.
He presented results of a study based on data from the Pregnancy Influenza Vaccine Effectiveness Network (PREVENT), which included public health or health care systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and three states (California, Oregon, and Washington). The study included women aged 18-50 years who were pregnant during local influenza seasons from 2010 to 2016. Most of the women were older than 35 years (79%), and in the third trimester (65%), and had no high risk medical conditions (66%). The study was published in Clinical Infectious Diseases (2018 Oct 11. doi: 10.1093/cid/ciy737).
The researchers identified 19,450 hospitalizations with an acute respiratory or febrile illness discharge diagnosis and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for flu viruses. Of these, 1,030 (6%) of the women underwent rRT-PCR testing, 54% were diagnosed with either influenza or pneumonia, and 58% had detectable influenza A or B virus infections.
Overall, the adjusted IVE was 40%; 13% of rRT-PCR-confirmed influenza-positive pregnant women and 22% of influenza-negative pregnant women were vaccinated; IVE was adjusted for site, season, season timing, and high-risk medical conditions.
“The takeaway is this is the average performance of the vaccine across multiple countries and different seasons,” and the vaccine effectiveness appeared stable across high-risk medical conditions and trimesters of pregnancy, Dr. Thompson said.
The generalizability of the study findings was limited by the lack of data from low- to middle-income countries, he said during the meeting discussion. However, the ICU admission rate is “what we would expect” and similar to results from previous studies. The consistent results showed the need to increase flu vaccination for pregnant women worldwide and to include study populations from lower-income countries in future research.
Dr. Thompson had no financial conflicts to disclose.
FROM AN ACIP MEETING