A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

A Food and Drug Administration advisory committee has voted 11 to 2 against a recommendation that the agency approve a long-studied antiarrhythmic agent for cardioversion of recent-onset atrial fibrillation (AFib).

It was the second time before an FDA advisory panel for vernakalant (Brinavess, Correvio International Sàrl), which the agency had declined to approve in 2008 due to safety concerns. That time, however, its advisors had given the agency a decidedly positive recommendation.

Since then, registry data collected for the drug’s resubmission seemed only to raise further safety issues, especially evidence that a single infusion may cause severe hypotension and suppress left ventricular function.

Some members of the Cardiovascular and Renal Drugs Advisory Committee (CRDAC), including a number who voted against approval, expressed hopes for further research aimed at identifying specific AFib patient groups who might safely benefit from vernakalant.

Of note, the drug has long been available for AFib cardioversion in Europe, where there are a number of other pharmacologic options, and was recently approved in Canada.

“We do recognize there’s a significant clinical need here,” observed Paul M. Ridker, MD, MPH, of Harvard Medical School and Brigham and Women’s Hospital Boston, a CRDAC panelist.

The results of the safety study that Correvio presented to the panel were “pretty marginal,” Dr. Ridker said. Given the negative safety signals and the available cardioversion alternatives, he questioned whether vernakalant represented a “substantial advance versus just another option. Right now, I’m not convinced it’s a substantial advance.”

FDA representatives were skeptical about vernakalant when they walked into the meeting room, as noted in briefing documents they had circulated beforehand. The drug’s safety experience under consideration included one case of ventricular arrhythmia and cardiogenic shock in a treated patient without apparent structural heart disease, who subsequently died. That case was much discussed throughout the meeting.

In its resubmission of vernakalant to regulators, Correvio also pointed to a significant unmet need for AFib cardioversion options in the United States, given the few alternatives.

For example, ibutilide is FDA-approved for recent-onset AFib or atrial flutter; but as the company and panelists noted, the drug isn’t often used for that indication. Patients with recent-onset AFib are often put on rate-control meds without cardioversion. Or clinicians may resort to electrical cardioversion, which can be logistically cumbersome and require anesthesia and generally a hospital stay.

Oral or intravenous amiodarone and oral dofetilide, flecainide, and propafenone are guideline-recommended but not actually FDA-approved for recent-onset AFib, the company noted.

Correvio made its “pre-infusion checklist” a core feature of its case. It was designed to guide selection of patients for vernakalant cardioversion based on contraindications such as a systolic blood pressure under 100 mm Hg, severe heart failure, aortic stenosis, severe bradycardia or heart block, or a prolonged QT interval.

In his presentation to the panel, FDA medical officer Preston Dunnmon, MD, said the safety results from the SPECTRUM registry, another main pillar of support for the vernakalant resubmission, “are not reassuring.”

As reasons, Dr. Dunnmon cited likely patient-selection bias and its high proportion of patients who were not prospectively enrolled; 21% were retrospectively entered from records.

Moreover, “the proposed preinfusion checklist will not reliably predict which subjects will experience serious cardiovascular adverse events with vernakalant,” he said.

“Vernakalant has induced harm that cannot be reliably predicted, prevented, or in some cases, treated. In contrast to vernakalant, electrical cardioversion and ibutilide pharmacologic cardioversion can cause adverse events, but these are transient and treatable,” he said.

Many on the panel agreed. “I thought the totality of evidence supported the hypothesis that this drug has a potential for a fatal side effect in a disease that you can live with, potentially, and that there are other treatments for,” said Julia B. Lewis, MD, Vanderbilt Medical Center, Nashville, Tenn., who chaired the CRDAC panel.

“The drug clearly converts atrial fibrillation, although it’s only transient,” observed John H. Alexander, MD, MHSc, Duke University, Durham, N.C., one of the two panelists who voted to recommend approval of vernakalant.

“And, there clearly is a serious safety signal in some populations of patients,” he agreed. “However, I was more reassured by the SPECTRUM data.” There is likely to be a low-risk group of patients for whom vernakalant could represent an important option that “outweighs the relatively low risk of serious complications,” Dr. Alexander said.

“So more work needs to be done to clarify who are the low risk patients where it would be favorable.”

Panelist Matthew Needleman, MD, Walter Reed National Military Medical Center, Bethesda, Md., also voted in favor of approval.

“We’ve all known patients with normal ejection fractions who keep coming in with symptomatic atrial fib, want to get out of it quickly, and get back to their lives. So having an option like this I think would be good for a very select group of patients,” Dr. Needleman said.

But the preinfusion checklist and other potential ways to select low-risk patients for vernakalant could potentially backfire, warned John M. Mandrola, MD, Baptist Medical Associates, Louisville, Ky., from the panel.

The FDA representatives had presented evidence that the drug can seriously depress ventricular function, and that the lower cardiac output is what leads to hypotension, he elaborated in an interview after the meeting.

If the checklist is used to exclude hemodynamically unstable patients from receiving vernakalant, he said, “Then you’re really giving this drug to relatively healthy patients for convenience, to decrease hospitalization or the hospital stay.”

The signal for substantial harm, Dr. Mandrola said, has to be balanced against that modest benefit.

Moreover, those in whom the drug doesn’t work may be left in a worse situation, he proposed. Only about half of patients are successfully converted on vernakalant, the company and FDA data suggested. The other half of patients who don’t achieve sinus rhythm on the drug still must face the significant hazards of depressed ejection fraction and hypotension, a high price to pay for an unsuccessful treatment.

Dr. Mandrola is Chief Cardiology Correspondent for theheart.org | Medscape Cardiology; his disclosure statement states no relevant financial relationships.

This article first appeared on Medscape.com.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

BALTIMORE – Patients hospitalized for epilepsy may have higher odds of death if they have a secondary diagnosis of arrhythmia, whereas the presence of apnea alone may not significantly increase mortality, according to an analysis of data from the Nationwide Inpatient Sample presented at the annual meeting of the American Epilepsy Society.

Jake Remaly/MDedge News

“If you have someone with arrhythmia and epilepsy, you have to be more concerned about possible SUDEP [sudden unexpected death in epilepsy],” relative to someone with apnea and epilepsy, said senior study author Sanjay P. Singh, MD, professor of neurology at Creighton University, Omaha, Neb.

Research indicates that apnea and cardiac arrhythmias may contribute to SUDEP, and the incidence of SUDEP is higher in patients with intractable epilepsy.

To identify the prevalence of apnea, arrhythmia, and both conditions in epilepsy hospitalizations, as well as the prevalence of intractable epilepsy and mortality, Dr. Singh and colleagues performed a retrospective, cross-sectional analysis of pediatric and adult epilepsy hospitalizations between 2003 and 2014 in the Nationwide Inpatient Sample. They determined apnea and arrhythmia diagnoses using ICD-9-CM codes.

Among more than 2.6 million epilepsy hospitalizations, the prevalence of apnea was 2.75%, the prevalence of arrhythmia was 8.91%, and the prevalence of both was 0.49%. The proportion of patients with intractable epilepsy was 7.7%. Among the more than 207,000 hospitalizations with intractable epilepsy, the prevalence of apnea was 3.62%, the prevalence of arrhythmia was 3.34%, and the prevalence of both was 0.36%. The prevalence trend of apnea, arrhythmia, and both together increased between 2003 and 2014.

“In univariate analysis, prevalence of mortality was highest among patients with arrhythmia,” the researchers reported, at – 3.1% in patients with arrhythmia versus 0.48% in patients with apnea, 2.91% in patients with both, and 0.46% in patients without apnea or arrhythmia.

In a multivariable regression analysis, significant and independent predictors of death included intractable epilepsy (odds ratio, 1.17), apnea (OR, 0.84), arrhythmia (OR, 3.29), and the presence of both apnea and arrhythmia (OR, 3.24). When hospitalization was complicated by intractable epilepsy, the odds of death rose with the presence of apnea (OR, 2.07), arrhythmia (OR, 8.39), and with both apnea and arrhythmia (OR, 11.64).

The results highlight the importance of effective epilepsy management, said first author Urvish K. Patel, MBBS, also with Creighton University. “If we can stop [conversion to intractable epilepsy], then this odds ratio can go down.”

Attention to arrhythmias, as well as the combination of arrhythmias and apnea, may “be important in identifying patients at risk for SUDEP,” the authors concluded.

The researchers had no disclosures and reported receiving no outside funding for their work.

[email protected]

SOURCE: Patel UK et al. AES 2019, Abstract 2.140.

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[polldaddy:10476065]

[polldaddy:10476065]

ATLANTA – Treatment of polyarticular-course juvenile idiopathic arthritis with tofacitinib led to significantly fewer disease flares and greater improvement in disease activity than with placebo in a phase 3, multinational, randomized, double-blind, controlled withdrawal study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Hermine I. Brunner, MD, director of the division of rheumatology at Cincinnati Children’s Hospital Medical Center, and colleagues conducted the study in 225 patients between 2 and less than 18 years old with polyarticular-course juvenile idiopathic arthritis (pJIA; n = 184), psoriatic arthritis (PsA; n = 20), or enthesitis-related arthritis (ERA; n = 21). Patients were included if they had an inadequate response or intolerance to a disease-modifying antirheumatic drug and active disease with five or more active joints in the case of pJIA and three or more active joints in PsA or ERA.

Dr. Brunner presented results only for pJIA patients; the results for PsA and ERA patients will be assessed and presented separately.

The researchers divided their study into two sections. In the open-label portion of the study, patients received twice-daily tofacitinib (Xeljanz) at a dose of 5 mg or a weight-based lower dose in patients under 40 kg for 18 weeks. A total of 173 patients met JIA ACR30 response criteria, defined as 30% or greater improvement in three of six JIA core set variables and worsening in no more than one of the core set variables, and then were randomized in part 2 of the study to continue the same dose of tofacitinib or receive placebo until 44 weeks. Dr. Brunner noted that most patients who discontinued treatment in parts 1 and 2 did so because of insufficient clinical response rather than from adverse events.

Disease flare occurrence between 18 and 44 weeks was measured as a primary endpoint, and key secondary endpoints included JIA ACR30/50/70 response and change in Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) scores from part 2 baseline. The researchers used a “gatekeeping approach” that sequenced outcome measures in their statistical analysis to control for false positives in primary and secondary outcomes, where statistical significance could be achieved only if the previous outcome in the sequence was statistically significant.

Patients had a median age of 13 years, and most were female, white (about 87%), and between one-third and one-half of patients were based in North America. JIA disease duration was a median of about 2.5 years, C-reactive protein was about 0.3 mg/dL, and median CHAQ-DI scores were about 0.9 across tofacitinib and placebo groups. Other baseline characteristics were balanced between the two groups, Dr. Brunner said.

“Patients with polyarticular-course JIA in the open-label study experienced a rapid improvement of their disease activity from very high to moderate within 18 weeks,” Dr. Brunner said in her presentation. “[T]ofacitinib demonstrated significantly greater efficacy versus placebo in patients with polyarticular-course JIA based on occurrence of fewer flares in part 2.”

Specifically, disease flare occurred in 29.2% of patients by 44 weeks in the tofacitinib group, compared with 52.9% of patients in the placebo group (P = .0031), for an overall 54% lower risk of flare among patients receiving tofacitinib (hazard ratio, 0.459; 95% confidence interval, 0.268-0.785; P = .0037). The response rate was higher for patients receiving tofacitinib at 44 weeks when measured by JIA ACR30 (70.8% vs. 47.1% with placebo; P = .0031) or by JIA ACR50 (66.7% vs. 47.1%; P = .0166) and JIA ACR70 criteria (54.2% vs. 37.1%; P = .0387). The change in CHAQ-DI score also improved at 44 weeks to a significantly greater extent in the tofacitinib group than with placebo (–0.09 vs. 0.03; P = .0292).

“The safety profile of tofacitinib in children with JIA was comparable to what you have seen or known in the [rheumatoid arthritis] population, and no new safety risks were identified in this pediatric population,” Dr. Brunner said.

The researchers reported ties with Pfizer, which funded the study, and more than two dozen other pharmaceutical companies.

SOURCE: Brunner HI et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L22.

ATLANTA – Treatment of polyarticular-course juvenile idiopathic arthritis with tofacitinib led to significantly fewer disease flares and greater improvement in disease activity than with placebo in a phase 3, multinational, randomized, double-blind, controlled withdrawal study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Hermine I. Brunner, MD, director of the division of rheumatology at Cincinnati Children’s Hospital Medical Center, and colleagues conducted the study in 225 patients between 2 and less than 18 years old with polyarticular-course juvenile idiopathic arthritis (pJIA; n = 184), psoriatic arthritis (PsA; n = 20), or enthesitis-related arthritis (ERA; n = 21). Patients were included if they had an inadequate response or intolerance to a disease-modifying antirheumatic drug and active disease with five or more active joints in the case of pJIA and three or more active joints in PsA or ERA.

Dr. Brunner presented results only for pJIA patients; the results for PsA and ERA patients will be assessed and presented separately.

The researchers divided their study into two sections. In the open-label portion of the study, patients received twice-daily tofacitinib (Xeljanz) at a dose of 5 mg or a weight-based lower dose in patients under 40 kg for 18 weeks. A total of 173 patients met JIA ACR30 response criteria, defined as 30% or greater improvement in three of six JIA core set variables and worsening in no more than one of the core set variables, and then were randomized in part 2 of the study to continue the same dose of tofacitinib or receive placebo until 44 weeks. Dr. Brunner noted that most patients who discontinued treatment in parts 1 and 2 did so because of insufficient clinical response rather than from adverse events.

Disease flare occurrence between 18 and 44 weeks was measured as a primary endpoint, and key secondary endpoints included JIA ACR30/50/70 response and change in Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) scores from part 2 baseline. The researchers used a “gatekeeping approach” that sequenced outcome measures in their statistical analysis to control for false positives in primary and secondary outcomes, where statistical significance could be achieved only if the previous outcome in the sequence was statistically significant.

Patients had a median age of 13 years, and most were female, white (about 87%), and between one-third and one-half of patients were based in North America. JIA disease duration was a median of about 2.5 years, C-reactive protein was about 0.3 mg/dL, and median CHAQ-DI scores were about 0.9 across tofacitinib and placebo groups. Other baseline characteristics were balanced between the two groups, Dr. Brunner said.

“Patients with polyarticular-course JIA in the open-label study experienced a rapid improvement of their disease activity from very high to moderate within 18 weeks,” Dr. Brunner said in her presentation. “[T]ofacitinib demonstrated significantly greater efficacy versus placebo in patients with polyarticular-course JIA based on occurrence of fewer flares in part 2.”

Specifically, disease flare occurred in 29.2% of patients by 44 weeks in the tofacitinib group, compared with 52.9% of patients in the placebo group (P = .0031), for an overall 54% lower risk of flare among patients receiving tofacitinib (hazard ratio, 0.459; 95% confidence interval, 0.268-0.785; P = .0037). The response rate was higher for patients receiving tofacitinib at 44 weeks when measured by JIA ACR30 (70.8% vs. 47.1% with placebo; P = .0031) or by JIA ACR50 (66.7% vs. 47.1%; P = .0166) and JIA ACR70 criteria (54.2% vs. 37.1%; P = .0387). The change in CHAQ-DI score also improved at 44 weeks to a significantly greater extent in the tofacitinib group than with placebo (–0.09 vs. 0.03; P = .0292).

“The safety profile of tofacitinib in children with JIA was comparable to what you have seen or known in the [rheumatoid arthritis] population, and no new safety risks were identified in this pediatric population,” Dr. Brunner said.

The researchers reported ties with Pfizer, which funded the study, and more than two dozen other pharmaceutical companies.

SOURCE: Brunner HI et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L22.

ATLANTA – Treatment of polyarticular-course juvenile idiopathic arthritis with tofacitinib led to significantly fewer disease flares and greater improvement in disease activity than with placebo in a phase 3, multinational, randomized, double-blind, controlled withdrawal study presented at the annual meeting of the American College of Rheumatology.

Jeff Craven/MDedge News

Hermine I. Brunner, MD, director of the division of rheumatology at Cincinnati Children’s Hospital Medical Center, and colleagues conducted the study in 225 patients between 2 and less than 18 years old with polyarticular-course juvenile idiopathic arthritis (pJIA; n = 184), psoriatic arthritis (PsA; n = 20), or enthesitis-related arthritis (ERA; n = 21). Patients were included if they had an inadequate response or intolerance to a disease-modifying antirheumatic drug and active disease with five or more active joints in the case of pJIA and three or more active joints in PsA or ERA.

Dr. Brunner presented results only for pJIA patients; the results for PsA and ERA patients will be assessed and presented separately.

The researchers divided their study into two sections. In the open-label portion of the study, patients received twice-daily tofacitinib (Xeljanz) at a dose of 5 mg or a weight-based lower dose in patients under 40 kg for 18 weeks. A total of 173 patients met JIA ACR30 response criteria, defined as 30% or greater improvement in three of six JIA core set variables and worsening in no more than one of the core set variables, and then were randomized in part 2 of the study to continue the same dose of tofacitinib or receive placebo until 44 weeks. Dr. Brunner noted that most patients who discontinued treatment in parts 1 and 2 did so because of insufficient clinical response rather than from adverse events.

Disease flare occurrence between 18 and 44 weeks was measured as a primary endpoint, and key secondary endpoints included JIA ACR30/50/70 response and change in Childhood Health Assessment Questionnaire Disability Index (CHAQ-DI) scores from part 2 baseline. The researchers used a “gatekeeping approach” that sequenced outcome measures in their statistical analysis to control for false positives in primary and secondary outcomes, where statistical significance could be achieved only if the previous outcome in the sequence was statistically significant.

Patients had a median age of 13 years, and most were female, white (about 87%), and between one-third and one-half of patients were based in North America. JIA disease duration was a median of about 2.5 years, C-reactive protein was about 0.3 mg/dL, and median CHAQ-DI scores were about 0.9 across tofacitinib and placebo groups. Other baseline characteristics were balanced between the two groups, Dr. Brunner said.

“Patients with polyarticular-course JIA in the open-label study experienced a rapid improvement of their disease activity from very high to moderate within 18 weeks,” Dr. Brunner said in her presentation. “[T]ofacitinib demonstrated significantly greater efficacy versus placebo in patients with polyarticular-course JIA based on occurrence of fewer flares in part 2.”

Specifically, disease flare occurred in 29.2% of patients by 44 weeks in the tofacitinib group, compared with 52.9% of patients in the placebo group (P = .0031), for an overall 54% lower risk of flare among patients receiving tofacitinib (hazard ratio, 0.459; 95% confidence interval, 0.268-0.785; P = .0037). The response rate was higher for patients receiving tofacitinib at 44 weeks when measured by JIA ACR30 (70.8% vs. 47.1% with placebo; P = .0031) or by JIA ACR50 (66.7% vs. 47.1%; P = .0166) and JIA ACR70 criteria (54.2% vs. 37.1%; P = .0387). The change in CHAQ-DI score also improved at 44 weeks to a significantly greater extent in the tofacitinib group than with placebo (–0.09 vs. 0.03; P = .0292).

“The safety profile of tofacitinib in children with JIA was comparable to what you have seen or known in the [rheumatoid arthritis] population, and no new safety risks were identified in this pediatric population,” Dr. Brunner said.

The researchers reported ties with Pfizer, which funded the study, and more than two dozen other pharmaceutical companies.

SOURCE: Brunner HI et al. Arthritis Rheumatol. 2019;71(suppl 10), Abstract L22.

The brains of medication-naive patients with major depressive disorder (MDD) exhibit interhemispheric structural imbalances in areas that regulate positive emotional processes, results of a small cross-sectional study suggest.

“To the best of our knowledge, asymmetric alterations in cortical thickness and subcortical volume in patients with MDD have not yet been reported,” wrote Zhiwei Zuo, of the department of radiology, Southwest Hospital, Army Medical University, Chongqing, China, and associates. “A comprehensive understanding of the cerebral pathophysiology changes in depression is essential and may lead to more targeted approaches for the prevention and treatment of MDD.”

The investigators enrolled 35 medication-naive, untreated patients with MDD from the hospital’s department of psychology, and 35 age-, gender-, and education-matched controls. Using whole-brain analysis, the investigators identified asymmetry in cortical thickness and subcortical volume that was mostly present in the cortical-striatal-pallidal-thalamic circuit. This part of the brain helps translate underlying positive affect processes into conscious feelings of pleasure, the authors reported. They noted that, although approaches to treating MDD previously have focused on diminishing negative emotional experiences, focusing instead on improving positive ones has begun to be taken more seriously in recent years (Clin Psychol Psychother. 2012 Jul-Aug;19[4]:326-40). The current study results were published in NeuroImage: Clinical.

Some limitations of the study include its small sample size and its cross-sectional nature. Nevertheless, they said, the findings could provide possible targets for therapeutic monitoring of the illness.

“These alterations were independent of depressive symptom severity, suggesting that cerebral asymmetry could be an appropriate indicator of morphological variations in mental disease,” the investigators noted.

The study was funded by the National Nature Science Foundation of China, the National Key Research and Development Plan of China, and the Innovative Talents Project of Southwest Hospital. The authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Zuo Z et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2018.101614.

The brains of medication-naive patients with major depressive disorder (MDD) exhibit interhemispheric structural imbalances in areas that regulate positive emotional processes, results of a small cross-sectional study suggest.

“To the best of our knowledge, asymmetric alterations in cortical thickness and subcortical volume in patients with MDD have not yet been reported,” wrote Zhiwei Zuo, of the department of radiology, Southwest Hospital, Army Medical University, Chongqing, China, and associates. “A comprehensive understanding of the cerebral pathophysiology changes in depression is essential and may lead to more targeted approaches for the prevention and treatment of MDD.”

The investigators enrolled 35 medication-naive, untreated patients with MDD from the hospital’s department of psychology, and 35 age-, gender-, and education-matched controls. Using whole-brain analysis, the investigators identified asymmetry in cortical thickness and subcortical volume that was mostly present in the cortical-striatal-pallidal-thalamic circuit. This part of the brain helps translate underlying positive affect processes into conscious feelings of pleasure, the authors reported. They noted that, although approaches to treating MDD previously have focused on diminishing negative emotional experiences, focusing instead on improving positive ones has begun to be taken more seriously in recent years (Clin Psychol Psychother. 2012 Jul-Aug;19[4]:326-40). The current study results were published in NeuroImage: Clinical.

Some limitations of the study include its small sample size and its cross-sectional nature. Nevertheless, they said, the findings could provide possible targets for therapeutic monitoring of the illness.

“These alterations were independent of depressive symptom severity, suggesting that cerebral asymmetry could be an appropriate indicator of morphological variations in mental disease,” the investigators noted.

The study was funded by the National Nature Science Foundation of China, the National Key Research and Development Plan of China, and the Innovative Talents Project of Southwest Hospital. The authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Zuo Z et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2018.101614.

The brains of medication-naive patients with major depressive disorder (MDD) exhibit interhemispheric structural imbalances in areas that regulate positive emotional processes, results of a small cross-sectional study suggest.

“To the best of our knowledge, asymmetric alterations in cortical thickness and subcortical volume in patients with MDD have not yet been reported,” wrote Zhiwei Zuo, of the department of radiology, Southwest Hospital, Army Medical University, Chongqing, China, and associates. “A comprehensive understanding of the cerebral pathophysiology changes in depression is essential and may lead to more targeted approaches for the prevention and treatment of MDD.”

The investigators enrolled 35 medication-naive, untreated patients with MDD from the hospital’s department of psychology, and 35 age-, gender-, and education-matched controls. Using whole-brain analysis, the investigators identified asymmetry in cortical thickness and subcortical volume that was mostly present in the cortical-striatal-pallidal-thalamic circuit. This part of the brain helps translate underlying positive affect processes into conscious feelings of pleasure, the authors reported. They noted that, although approaches to treating MDD previously have focused on diminishing negative emotional experiences, focusing instead on improving positive ones has begun to be taken more seriously in recent years (Clin Psychol Psychother. 2012 Jul-Aug;19[4]:326-40). The current study results were published in NeuroImage: Clinical.

Some limitations of the study include its small sample size and its cross-sectional nature. Nevertheless, they said, the findings could provide possible targets for therapeutic monitoring of the illness.

“These alterations were independent of depressive symptom severity, suggesting that cerebral asymmetry could be an appropriate indicator of morphological variations in mental disease,” the investigators noted.

The study was funded by the National Nature Science Foundation of China, the National Key Research and Development Plan of China, and the Innovative Talents Project of Southwest Hospital. The authors had no conflicts of interest to disclose.

[email protected]

SOURCE: Zuo Z et al. Neuroimage Clin. 2019. doi: 10.1016/j.nicl.2018.101614.

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

The Food and Drug Administration is investigating whether forms of the type 2 diabetes drug metformin that are available in the United States contain the genotoxic nitrosamine, N-nitrosodimethylamine (NDMA).

This follows reports of low-level NDMA contamination of metformin in other countries and of a few regulatory agencies issuing recalls for the drug, according to a statement from Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research.

“There are no metformin recalls affecting the U.S. market at this time,” the agency emphasized in the statement. It said NDMA levels in affected medication have been low, at or even below the acceptable intake limit, and there is currently no evidence indicating that metformin drugs within the United States or European Union have been contaminated.

The FDA advised that patients should continue taking metformin alone or in combination with other drugs to control their diabetes and that it would be dangerous for them to stop taking the medication without first discussing it with their providers. It also recommended that providers continue to use metformin when “clinically appropriate” while the investigation is underway as there are no alternative therapies to treat the disease in the same way.

NDMA is a common contaminant that is found in water and some foods and has probable carcinogenic effects when exposure is too high. The acceptable daily intake for NDMA in the United States is 96 ng/day, according to the statement, though people who take in that amount or less every day for 70 years are not expected to have an increased risk of cancer.

Both the FDA and its counterpart, the European Medicines Agency, have recently investigated the presence of NDMA impurities in ranitidine, a drug used to reduce production of stomach acid, which led to several manufacturers issuing recalls for it.

The agencies have also investigated angiotensin II receptor blockers, which are used to treat hypertension, heart failure, and high blood pressure.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The presence of NDMA “can be related to the drug’s manufacturing process or its chemical structure or even the conditions in which they are stored or packaged. As food and drugs are processed in the body, nitrosamines, including NDMA, can be formed,” Dr. Woodcock noted in the statement.

“We are monitoring this issue closely to assess any potential impact on patients with diabetes,” said Robert W. Lash, MD, chief professional and clinical affairs officer of the Endocrine Society. “We have members around the world and are concerned about the possibility of carcinogenic impurities in medications, both in the United States and elsewhere.”

[email protected]

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶

Contest unfounded views. Other common parental concerns about effects of HPV vaccine include supposed promotion of promiscuity, increased incidence of premature ovarian failure or insufficiency (POI), and increased risk of Guillain-Barré Syndrome (GBS), often propagated through published reports, media coverage, Web sites, and social media. Assure worried parents that many studies have shown that receipt of the vaccine is safe and does not lead to initiation of sexual activity or promiscuity, and, in fact, safer sexual health practices have been observed following vaccination.^57-59

Continue to: A large longitudinal...

In one study, 65% of parents expected to be reminded of any needed HPV vaccine doses, while 52% of the pediatric PCPs relied on parents to schedule subsequent immunizations.

A large longitudinal adolescent health survey administered in British Columbia looked at sexual health behaviors and risk factors in adolescent girls before and after receipt of HPV vaccination (2003, 2008, 2013).⁵⁹ Results showed no significant change in the reported number of sexual partners (2003-2013), increased reported use of contraception and condoms, and lower pregnancy rates.⁵⁹ There is no evidence that HPV vaccines cause reproductive problems in women⁵³; a review of VAERS reports from 2009 through 2015 did not detect any safety concerns for POI or other reproductive problems in females.⁶⁰ A 2018 population-based study of nearly 200,000 women observed no increase of POI following receipt of HPV vaccination.⁶¹ In addition, several recent studies have shown no increased risk for GBS following receipt of HPV vaccine.^62-64

CORRESPONDENCE
Pamela G. Rockwell, DO, FAAFP, 24 Frank Lloyd Wright Drive, SPC 5795, Room 2300, Lobby H, Ann Arbor, MI 48105; [email protected].

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶

Contest unfounded views. Other common parental concerns about effects of HPV vaccine include supposed promotion of promiscuity, increased incidence of premature ovarian failure or insufficiency (POI), and increased risk of Guillain-Barré Syndrome (GBS), often propagated through published reports, media coverage, Web sites, and social media. Assure worried parents that many studies have shown that receipt of the vaccine is safe and does not lead to initiation of sexual activity or promiscuity, and, in fact, safer sexual health practices have been observed following vaccination.^57-59

Continue to: A large longitudinal...

In one study, 65% of parents expected to be reminded of any needed HPV vaccine doses, while 52% of the pediatric PCPs relied on parents to schedule subsequent immunizations.

A large longitudinal adolescent health survey administered in British Columbia looked at sexual health behaviors and risk factors in adolescent girls before and after receipt of HPV vaccination (2003, 2008, 2013).⁵⁹ Results showed no significant change in the reported number of sexual partners (2003-2013), increased reported use of contraception and condoms, and lower pregnancy rates.⁵⁹ There is no evidence that HPV vaccines cause reproductive problems in women⁵³; a review of VAERS reports from 2009 through 2015 did not detect any safety concerns for POI or other reproductive problems in females.⁶⁰ A 2018 population-based study of nearly 200,000 women observed no increase of POI following receipt of HPV vaccination.⁶¹ In addition, several recent studies have shown no increased risk for GBS following receipt of HPV vaccine.^62-64

CORRESPONDENCE
Pamela G. Rockwell, DO, FAAFP, 24 Frank Lloyd Wright Drive, SPC 5795, Room 2300, Lobby H, Ann Arbor, MI 48105; [email protected].

Overall adolescent vaccination coverage is improving in the United States.¹ But for adolescents up to 15 years of age, there’s a large gap between the rate of vaccination for human papillomavirus (HPV) and the higher rates of coverage for tetanus, diphtheria, and acellular pertussis (Tdap) and meningococcal conjugate (MenACWY) vaccines.¹ Adopting or refining practice customs reviewed in this article can increase HPV vaccination rates and continue to improve coverage of all vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for adolescents between the ages of 11 and 12.

The evolution of ACIP’s HPV vaccine recommendations

Before December 2016, ACIP recommended a 3-dose HPV series for all adolescents between the ages of 11 and 12, given on a 0, 1-2, and 6-month schedule.² The series could be started at 9 years of age. It could be administered to females as old as 26 years, and to males through 21 years (or ages 22-26 years for those who wish to be vaccinated, who have certain medical conditions, or who are included in special populations—ie, gay and bisexual men, men who have sex with men, immunocompromised men, men with human immunodeficiency virus [HIV], and transgender men).

In 2016, ACIP revised its recommendation for adolescents who initiate vaccination before their 15th birthday: a 2-dose schedule is adequate, with the second dose given 6 to 12 months after the first dose. For those who initiate vaccination on or after their 15th birthday, and for those with certain medical conditions, the recommendation remains 3 doses on a 0, 1-2, and 6-month schedule.³

As of August 2019,⁴ ACIP now recommends that all women and men receive catch-up HPV vaccination through age 26. For individuals 27 to 45 years of age who have not been adequately vaccinated, HPV vaccine may be given based on shared clinical decision making with their physician.

How are we doing?

Overall, adolescent vaccination coverage is improving in the United States (see “Vaccination goals from ACIP and Healthy People 2020”^1,5,6), but the rate of improvement of HPV coverage is lower than that for Tdap and MenACWY coverage by age 15 years (although completion of the ­MenACWY vaccine series is low). From 2015 to 2016, coverage increased for 1 or more doses of Tdap, from 86.4% to 88% among 17-year olds (87.9% for 15-year olds), and coverage for 1 or more doses of MenACWY increased from 81.7% to 83.5% among 17-year olds (80.4% among 15-year olds).¹ Both Tdap and MenACWY coverage rates have surpassed Healthy People 2020 goals of 80%, and the focus now is on maintenance of coverage. Data from the 2016 National Immunization Survey ­(NIS)-Teen show that completion of the HPV vaccine series (applying updated HPV vaccine recommendations retrospectively) increased to 45.4% for 15-year-olds,¹ still far below the Healthy People 2020 goal of 80%. Completion rates for 2 or more doses of MenACWY also increased from 33.3% to 39.1%.¹

Common barriers to improved vaccine coverage

Barriers to improved vaccination rates include a lack of regular assessment of vaccine status; limited use of electronic records, tools, and immunization registries; lack of health care provider knowledge on current vaccine recommendations; vaccine costs; missed opportunities; and patient/parent refusals.^7,8 The Community Preventive Services Task Force outlines several well-established evidence-based ways that administrators and physicians can counter these barriers:

• give a strong recommendation to vaccinate,^9,10
• incorporate an audit/feedback mechanism for health care providers who vaccinate,^9,11
• use electronic alerts to remind health care providers to vaccinate,^9,12
• use your state’s electronic immunization information systems (IIS),^7,13
• appoint a vaccine practice team/­vaccine champion,^9,14 and
• implement standing orders and ­reminder/recall systems.^7,9,15

In 2016, 45.4% of 15-year-olds had completed the HPV vaccine series—far below the Healthy People 2020 goal of 80%.

The passage of the Affordable Care Act (ACA)—which mandates that certain preventive services, including ACIP-recommended immunizations, be covered as part of basic care at no cost-sharing—reduces the once-common financial barrier to vaccine uptake.¹⁶ A key contributor to low uptake of HPV vaccination by adolescents is parental refusal.¹⁷

Continue to: The threats posed by HPV

HPV infections are the most commonly transmitted infections in the United States and nearly all men and women will be exposed to one or more types of HPV at some point in their lives. Current data show that 79 million Americans, most in their late teens and early 20s, are infected with HPV, and about 14 million people in the United States become newly infected each year.¹⁸ HPV is a DNA tumor virus that causes epithelial proliferation at cutaneous and mucosal surfaces.

There are more than 100 types of the virus,¹⁹ including more than 40 strains that infect the human genital tract. Of the latter 40 strains, there are oncogenic or high-risk types and non-oncogenic or low-risk types.²⁰ HPV infection with high-risk types causes cervical, vaginal, and vulvar cancers in women; penile cancers in men; and oropharyngeal and anal cancers in both men and women. Low-risk HPV types cause genital warts in both men and women.²¹ The current available HPV vaccine in the United States is a 9-valent vaccine (9vHPV) that replaces the former 2- and 4-valent HPV vaccines and includes immunogenic coverage against high-risk HPV types 16, 18, 31, 33, 45, 52, and 58; and low-risk types 6 and 11.²²

Centers for Disease Control and Prevention (CDC) data from 2010 to 2014 show that approximately 23,700 women and approximately 17,300 men in the United States developed HPV-associated cancer. Most common in women are cervical cancers and in men, oropharyngeal cancers (cancers of the back of the throat, base of the tongue, and tonsils). Using population-based data to genotype HPV types from cancer tissues, the CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.²³ A significant percentage of these cancers could potentially be prevented by receipt of 9vHPV.^23,24

Make adolescent immunization a high priority

Anticipate opportunities to vaccinate and take steps to make your immunization and scheduling processes more prominent. With HPV specifically, you can strongly advocate for vaccination, address parental misgivings and educate them using clear communication styles, and acquire knowledge to answer concerns about potential vaccine adverse ­effects.

Every visit is an opportunity to vaccinate. The American Academy of Family Physicians and The American Academy of Pediatrics recommend that adolescents have annual preventive visits for screening, immunizations, and assessment and counseling for risky behaviors. However, many adolescents do not present annually for preventive visits, and fewer than half of adolescents receive regular preventive care.²⁵ In a study of 425 family physicians and pediatricians, almost all pediatricians endorsed the importance of annual well visits, while less than three-quarters of family physicians did.²⁶ An analysis of national surveillance systems shows rates for preventive health care visits range from 43% to 74% among adolescents 10 to 17 years of age, and 26% to 58% among young adults 18 to 25 years of age.²⁷ Overall, 67% of adolescent health care visits are for acute care, and 10% are for follow-up care.²⁸

Continue to: Missed opportunities for the HPV vaccine

Missed opportunities for the HPV vaccine. One study showed that at least 86% of unvaccinated adolescents had missed opportunities to receive HPV vaccine.²⁹ A study of 14,588 adolescent girls from January 2010 through August 2015 showed that HPV vaccine was given at only 37.1% of visits in which MenACWY or Tdap vaccines were administered.³⁰ The rate of HPV vaccination was just 26% during well adolescent visits, and 41.8% during all other primary care visits.³⁰ Every adolescent health care visit—including visits for acute care, chronic care, follow-up, or office-based procedures—is an opportunity to review vaccination status.

Give vaccines concomitantly (simultaneously or same-day). ACIP counsels that minor illnesses, such as mild upper respiratory infections with or without low-grade fever, are not contraindications to routine vaccination.³⁰ Also, the safety of simultaneous vaccine administration, often a concern of both parents and health care providers, has been well established. Each vaccine’s immunogenicity and safety profile are maintained when given concomitantly with other vaccines, and fewer visits are needed to complete an adolescent’s vaccination status.^31,32

Immediately schedule follow up visits and use reminder/recall systems. Parents of adolescents who opt for HPV vaccination are not always aware of the timing of the 2- or 3-dose schedule and may not even be aware that more than 1 dose of vaccine is recommended.

In a study of 14,588 adolescent girls who had vaccinations at an office visit, only 37.1% also received the HPV vaccine.

A qualitative study of pediatric primary care providers and parents/guardians of adolescent patients showed that for HPV vaccination series completion, 65% of parents/guardians expected to be reminded of any needed doses, while 52% of the pediatric primary care providers relied on parents to schedule subsequent immunizations, and often the HPV series was not completed.³³ Higher completion rates of the HPV vaccination series were achieved when follow-up appointments were scheduled at checkout for the 2nd or 3rd vaccine dose after initiation of HPV vaccination.³³ The use of patient reminder/recall systems using telephone calls or mailings (phone usage is more effective than mailings) is also shown to improve vaccination completion rates.³⁴

Recommend HPV vaccination clearly and resolutely

In a cross-sectional survey of 800 parents of adolescents ages 9 to 14 years, HPV vaccine was deemed the least likely vaccine to have been “very strongly” recommended by their health care provider, compared with the strength of recommendations for influenza, Tdap, and MenACWY vaccines.³⁵ The strength of a health care provider’s recommendation to vaccinate is the single most influential factor in vaccine uptake.^10,36,37 Most family physicians self-report “always recommending standard pediatric vaccines”; however, only a minority are following ACIP recommendations.³⁸ A national study reported that only about two-thirds of parents who received HPV vaccine recommendations perceived a high level of health care provider endorsement.³⁹ The takeaway point: Give a clear, unambiguous, strong recommendation to vaccinate with HPV to prevent infection; cervical, oropharyngeal, and other cancers; and genital warts.

Continue to: Tell parents why the timing is important

Tell parents why the timing is important. Inform parents that the HPV vaccine must be administered while their child is young (before the adolescent’s first sexual contact) to ensure the most robust immune response to the vaccine.⁴⁰ Unsolicited explanations about sexual activity need not be offered when discussing HPV vaccination, as it is fair to assume that sexual contact is a reality for nearly all people in their adolescent or adult life; and by extension, most sexually active people will likely have exposure to HPV at some time in their lives. By adulthood, sexual activity is nearly universal: The National Longitudinal Study of Adolescent Health showed that only about 3% of participants tracked since adolescence reported no sexual experience by (average age) 28.5 years.⁴¹

How you say it matters. Many pediatricians and family physicians report recommending HPV vaccine inconsistently, behind schedule, or without urgency,⁴² sending mixed messages by failing to endorse HPV vaccination strongly, failing to differentiate it from other vaccines, and presenting it as an “optional” vaccine that could be delayed.⁴³ Physicians and other health care providers who begin conversations about HPV vaccine by saying that the adolescent is “due” for the vaccine show higher vaccine recommendation quality scores than those who give unsolicited information about the vaccine, elicit questions before recommendation, or present the vaccine as an “option.”⁴² Parents who are “on the fence” may hesitate and decline HPV vaccination with a halfhearted recommendation.⁴⁴

The CDC reports that HPV is responsible for about 90% of cervical and anal cancers, 70% of oropharyngeal, vaginal, and vulvar cancers, and 60% of penile cancers.

“Your child is due for his/her Tdap, HPV, influenza, and meningococcal vaccinations to prevent potentially devastating disease and several cancers. I highly recommend all 4 vaccinations today” is more persuasive than, “I recommend your child receive his/her Tdap, meningococcal, and influenza vaccines. And we can also discuss the HPV vaccine.”

Direct presumptive language that assumes vaccine delivery is associated with higher odds of HPV vaccine acceptance and same-day agreement to vaccination than is an open-ended participatory conversational style.⁴⁵ Saying, “I believe in the importance of this cancer-preventing vaccine for your child” is more persuasive than saying, “What do you think about starting the HPV vaccination series today?”⁴⁶

Don’t give up when parents initially refuse HPV vaccinations for their adolescents. Parents’ decisions about HPV vaccination may change over time. Repeated positive recommendations and counseling for HPV vaccination over multiple visits have been shown in a large multivariable analysis to increase parent acceptance of HPV vaccination: 45% of parents reported secondary acceptance of HPV vaccination, and an additional 24% intended to vaccinate in the next 12 months.⁴⁷ Combining a presumptive communication style with motivational interviewing and a fact sheet has contributed to higher clinician-perceived levels of parental HPV vaccine acceptance and increased vaccination rates.⁴⁸

Continue to: Know how to address parents' concerns about safety

Know how to address parents’ concerns about safety

Be prepared to discuss and answer parents’ questions or concerns regarding any vaccine, especially the HPV vaccine. Social networks are important in parents’ vaccination decision-making,⁴⁹ and they may seek information from such sources as Twitter, Facebook, Google, and YouTube, where misinformation may be disseminated. A quantitative analysis of 560 YouTube videos relaying a false link between vaccines and autism or other serious adverse effects on children were uploaded between December 2007 and July 2017, with a peak of 224 videos uploaded in the first 7 months of 2017.⁵⁰ Most were negative in tone and dispensed misinformation.⁵⁰

The National Vaccine Information Center (NVIC) is an organization that takes a skeptical view of the US government and pharmaceutical companies. NVIC is widely criticized by scientists and leaders in vaccine science and public health as spreading false information on the risks of vaccines and, specifically, that HPV vaccination causes chronic disease. NVIC reports that receipt of HPV vaccine may increase the risk for cervical cancer and death.⁵¹ Pediatrician and vaccine researcher Dr. Paul Offit, interviewed by The Lancet in response to NVIC and other anti-vaccine groups’ messages, stated: “anti-vaccination organizations are unequivocally threatening public health.”⁵²

Describe the robust safety-monitoring system. The CDC is aware of public concern about the safety of HPV vaccine. Ongoing monitoring of vaccine safety and studies conducted by the CDC, the Food and Drug Administration (FDA), and other organizations has documented a reassuring safety record since the vaccine’s introduction in 2006.⁵³ Assure parents that the Vaccine Adverse Event Reporting System (VAERS) summary of 7244 reports following 9vHPV vaccination (December 1, 2014 – December 31, 2017) showed that most (97%) reports were nonserious: No new safety signals or unexpected patterns were observed, confirming consistency of the safety profile of 9vHPV with data from pre-licensure trials and post-licensure data on 4vHPV.⁵⁴

Acknowledge the usually mild, transient potential risks of HPV vaccination as reported to VAERS: local injection site symptoms such as pain, redness, or swelling in the arm where the injection was given (most common adverse effect), dizziness, fainting, headache, nausea, and fever.⁵³ Point out that fainting after vaccination is common in adolescents⁵⁵ and that the CDC and ACIP recommend observation of adolescents for 15 minutes following HPV vaccination.⁵⁶ Consider this 15-minute observation period after adolescent receipt of any vaccine to be part of standard practice in your vaccination setting.⁵⁶

Contest unfounded views. Other common parental concerns about effects of HPV vaccine include supposed promotion of promiscuity, increased incidence of premature ovarian failure or insufficiency (POI), and increased risk of Guillain-Barré Syndrome (GBS), often propagated through published reports, media coverage, Web sites, and social media. Assure worried parents that many studies have shown that receipt of the vaccine is safe and does not lead to initiation of sexual activity or promiscuity, and, in fact, safer sexual health practices have been observed following vaccination.^57-59

Continue to: A large longitudinal...

In one study, 65% of parents expected to be reminded of any needed HPV vaccine doses, while 52% of the pediatric PCPs relied on parents to schedule subsequent immunizations.

A large longitudinal adolescent health survey administered in British Columbia looked at sexual health behaviors and risk factors in adolescent girls before and after receipt of HPV vaccination (2003, 2008, 2013).⁵⁹ Results showed no significant change in the reported number of sexual partners (2003-2013), increased reported use of contraception and condoms, and lower pregnancy rates.⁵⁹ There is no evidence that HPV vaccines cause reproductive problems in women⁵³; a review of VAERS reports from 2009 through 2015 did not detect any safety concerns for POI or other reproductive problems in females.⁶⁰ A 2018 population-based study of nearly 200,000 women observed no increase of POI following receipt of HPV vaccination.⁶¹ In addition, several recent studies have shown no increased risk for GBS following receipt of HPV vaccine.^62-64

CORRESPONDENCE
Pamela G. Rockwell, DO, FAAFP, 24 Frank Lloyd Wright Drive, SPC 5795, Room 2300, Lobby H, Ann Arbor, MI 48105; [email protected].

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

Compromise bipartisan legislation to address surprise medical bills is getting push back from physician groups.

utah778/Thinkstock

Leadership from the House Energy and Commerce Committee and the Senate Health, Education, Labor, and Pensions Committee on Dec. 9 unveiled a compromise bill that includes rate-setting for small surprise billing and arbitration for larger ones at a lower threshold than what was originally proposed.

The new bill, part of a broader Lower Health Care Costs Act, would protect patients from surprise medical bills related to emergency care, holding them responsible for in-network cost-sharing rates for out-of-network care provided at an in-network facility without their informed consent. Out-of-network surprise bills would be applied to the patient’s in-network deductible.

Under the legislation, providers would be paid at minimum the local, market-based median in-network negotiated rate for services, with a median rate under a $750 threshold. When the median exceeds $750, the provider or insurer would be allowed to choose arbitration process to resolve payment disputes.

The bill also protects patients by banning out-of-network facilities and providers from sending balance bills for more than in-network cost-sharing amounts.

Physician groups, however, see the legislation as a giveback to insurers that puts health care professionals at a disadvantage when negotiating to be included in insurer networks.

At issue is the $750 threshold for optional arbitration.

“If you set the arbitration system in such a way that limits the ability of a physician to go to arbitration to settle a dispute between a health plan and the doctor, and if you say that can only be done when there [are] bills that are greater than $750 for a particular service, then the vast majority of services provided by doctors will not be able to go to arbitration,” Christian Shalgian, director of advocacy and health policy at the American College of Surgeons, said in an interview.

Cynthia Moran, executive vice president of government relations and health policy at the American College of Radiology, agreed.

“This particular product is going in a direction that we’re not comfortable with so we can’t support it on the basis of the benchmarks and the independent dispute resolution (IDR) process with the $750 threshold,” she said in an interview. The services radiologists provide tend to be in the $100-200 range, she said, so that would automatically exclude them from accessing arbitration. She also said that it is her understanding that many physician services will fall under that $750 threshold.

“That $750 is really going to mean that the vast majority of this policy is a benchmark-driven policy,” she said. “It is not going to be an IDR-driven policy and that is the crux of our objection to it.”

And by taking arbitration off the table, insurers have no incentive to negotiate in good faith with doctors to ensure that doctors are getting paid for the services they perform.

“For those situations where there is an out-of-network physician at an in-network facility, we believe that the patient should not have to pay any more for those emergency situations where they patient doesn’t get to choose their doctor,” Mr. Shalgian said. “The dispute really comes down to how much does the health plan have to pay the doctor.”

He noted that the legislation ties the rate to median in-network rates “and that’s a problem for us as well because of the fact that [this is] going to allow the health plans to set median in-network rates as the rate that they can pay the doctors.”

If the bill becomes law, “when you have a situation where you have an in-network physician trying to negotiate with a health plan to stay in network, that health plan now has more power in that negotiation because if [the physician] is making more than median in-network rates, then the health plan can say, ‘go out of network because we will just pay you median in-network’ at that point. That is a significant concern to us as well.”

Mr. Shalgian said that the ideal solution would be to eliminate the threshold entirely and just send disputes to arbitration. Recognizing that it might not be practical, the $750 threshold should be lowered.

ACS supported a $300 threshold, he added.

The bill is expected to be tacked on to one of the mandatory spending bills that Congress needs to pass by the end of the year.

The $750 threshold would be a savings generator for the government and an important bill such as this should be passed on its own merits, Mr. Shalgian said.

Ms. Moran called for Congress to take its time with the legislation.

“We do think that this whole issue needs more time for everyone to understand what the impact is on this first run of the solution and we think it should be slowed down a bit,” she said. “It should not go to the floor until you hear more from the providers [after] the providers figure out what the impact will be.”

The American Medical Association also called for Congress to slow down.

“The current proposal relies on benchmark rate setting that would serve only to benefit the bottom line of insurance companies at the expense of patients seeking a robust network of physicians for their care,” AMA President Patrice Harris, MD, said in a statement. “Rather than rushing to meet arbitrary deadlines, it is important to get this legislation right.”

[email protected]

In the roundtable article, “The electronic medical record’s role in ObGyn burnout and patient care” (October 2019), Megan L. Evans, MD, MPH; John J. Dougherty, MD, MBA; and Mark B. Woodland, MS, MD, discussed burnout’s connection with the electronic medical record (EMR) and solutions implemented at their institutions to help cope with the problem. They highlighted changes they felt their EMR systems needed to undergo. In addition, they noted as a whole that the EMR has not improved patient care.

OBG Management polled readers to see their thoughts on this question: “Do you think that the EMR has improved patient care?”

In the roundtable article, “The electronic medical record’s role in ObGyn burnout and patient care” (October 2019), Megan L. Evans, MD, MPH; John J. Dougherty, MD, MBA; and Mark B. Woodland, MS, MD, discussed burnout’s connection with the electronic medical record (EMR) and solutions implemented at their institutions to help cope with the problem. They highlighted changes they felt their EMR systems needed to undergo. In addition, they noted as a whole that the EMR has not improved patient care.

OBG Management polled readers to see their thoughts on this question: “Do you think that the EMR has improved patient care?”

In the roundtable article, “The electronic medical record’s role in ObGyn burnout and patient care” (October 2019), Megan L. Evans, MD, MPH; John J. Dougherty, MD, MBA; and Mark B. Woodland, MS, MD, discussed burnout’s connection with the electronic medical record (EMR) and solutions implemented at their institutions to help cope with the problem. They highlighted changes they felt their EMR systems needed to undergo. In addition, they noted as a whole that the EMR has not improved patient care.

OBG Management polled readers to see their thoughts on this question: “Do you think that the EMR has improved patient care?”

A look across nearly 3 decades finds that more pediatricians are participating in global health activities than in the past, and more doctors are interested in future global health experiences.

Avatar_023/iStock/Getty Images

Lead author Kevin Chan, MD, MPH, of the University of Toronto, and colleagues analyzed the responses of 668 pediatricians from the 2017 American Academy of Pediatrics Periodic Survey and compared the data with responses from 638 pediatricians collected in the 1989 periodic survey about pediatricians’ global health experiences and interests. Findings showed that participation in global health activities rose from 2% in 1989 to 5% in 2017, while interest in future global health experiences grew from 25% in 1989 to 32% in 2017. The study was published in Pediatrics.

Notable increases in global health participation were found in women (1% in 1989 to 5% in 2017) and men (3% in 1989 to 6% in 2017), subspecialists (3% in 1989 to 9% in 2017), and pediatricians who worked in medical school, hospital, or clinic settings (3% in 1989 to 8% in 2017).

In terms of age, pediatricians 50 years or older had a higher rate of a recent global health experience, with the largest increase in global health participation occurring in pediatricians 60 years and older (2% in 1989 to 9% in 2017), the study found.

Similarly, interest in future global health activities increased during the same time period for male and female pediatricians, for generalists and subspecialists, and for those working in medical school, hospital, or clinic settings. Clinical care and teaching settings were the most common preferences for future global health experiences in both 1989 and 2017. Administration and research were the least likely selected preferences in both surveys. Pediatricians affiliated with an academic institution, hospital, or clinic were more likely to have recently engaged in a global health activity and also were more likely express interest in such an opportunity, compared with solo pediatricians or those in small practices.

In an editorial accompanying the article, Suzinne Pak-Gorstein, MD, MPH, PhD, of the University of Washington, Seattle, said that the study highlights the importance of preparation for pediatricians who seek global health opportunities, particularly experiences that are short term.

“Ethical approaches to international work should be thoughtful and intentional, such as deciding to work with organizations that offer short-term experiences only in the context of long-term partnerships, considering the burden on local partners for hosting visitors, and insisting on a commitment to equitable collaborations that are mutually beneficial,” she wrote.

Dr. Pak-Gorstein added that future innovations in global health education can inspire learning experiences for pediatricians that utilize their passion and enthusiasm, while also enabling them to become more globally minded.

“In this way, pediatricians can be empowered to understand the world’s daunting challenges; respect cultural, religious, and socioeconomic differences; and facilitate dialogue and solutions for improving child health worldwide,” she concluded.

The survey was funded by the American Academy of Pediatrics. The study authors had no relevant financial disclosures. Dr. Pak-Gorstein said she received no funding for the editorial and had no relevant financial disclosures.

[email protected]

SOURCE: Chan K et al. Pediatrics. 2019 Dec 10. doi: 10.1542/peds.2019-1655.

A look across nearly 3 decades finds that more pediatricians are participating in global health activities than in the past, and more doctors are interested in future global health experiences.

Avatar_023/iStock/Getty Images

Lead author Kevin Chan, MD, MPH, of the University of Toronto, and colleagues analyzed the responses of 668 pediatricians from the 2017 American Academy of Pediatrics Periodic Survey and compared the data with responses from 638 pediatricians collected in the 1989 periodic survey about pediatricians’ global health experiences and interests. Findings showed that participation in global health activities rose from 2% in 1989 to 5% in 2017, while interest in future global health experiences grew from 25% in 1989 to 32% in 2017. The study was published in Pediatrics.

Notable increases in global health participation were found in women (1% in 1989 to 5% in 2017) and men (3% in 1989 to 6% in 2017), subspecialists (3% in 1989 to 9% in 2017), and pediatricians who worked in medical school, hospital, or clinic settings (3% in 1989 to 8% in 2017).

In terms of age, pediatricians 50 years or older had a higher rate of a recent global health experience, with the largest increase in global health participation occurring in pediatricians 60 years and older (2% in 1989 to 9% in 2017), the study found.

Similarly, interest in future global health activities increased during the same time period for male and female pediatricians, for generalists and subspecialists, and for those working in medical school, hospital, or clinic settings. Clinical care and teaching settings were the most common preferences for future global health experiences in both 1989 and 2017. Administration and research were the least likely selected preferences in both surveys. Pediatricians affiliated with an academic institution, hospital, or clinic were more likely to have recently engaged in a global health activity and also were more likely express interest in such an opportunity, compared with solo pediatricians or those in small practices.

In an editorial accompanying the article, Suzinne Pak-Gorstein, MD, MPH, PhD, of the University of Washington, Seattle, said that the study highlights the importance of preparation for pediatricians who seek global health opportunities, particularly experiences that are short term.

“Ethical approaches to international work should be thoughtful and intentional, such as deciding to work with organizations that offer short-term experiences only in the context of long-term partnerships, considering the burden on local partners for hosting visitors, and insisting on a commitment to equitable collaborations that are mutually beneficial,” she wrote.

Dr. Pak-Gorstein added that future innovations in global health education can inspire learning experiences for pediatricians that utilize their passion and enthusiasm, while also enabling them to become more globally minded.

“In this way, pediatricians can be empowered to understand the world’s daunting challenges; respect cultural, religious, and socioeconomic differences; and facilitate dialogue and solutions for improving child health worldwide,” she concluded.

The survey was funded by the American Academy of Pediatrics. The study authors had no relevant financial disclosures. Dr. Pak-Gorstein said she received no funding for the editorial and had no relevant financial disclosures.

[email protected]

SOURCE: Chan K et al. Pediatrics. 2019 Dec 10. doi: 10.1542/peds.2019-1655.

A look across nearly 3 decades finds that more pediatricians are participating in global health activities than in the past, and more doctors are interested in future global health experiences.

Avatar_023/iStock/Getty Images

Lead author Kevin Chan, MD, MPH, of the University of Toronto, and colleagues analyzed the responses of 668 pediatricians from the 2017 American Academy of Pediatrics Periodic Survey and compared the data with responses from 638 pediatricians collected in the 1989 periodic survey about pediatricians’ global health experiences and interests. Findings showed that participation in global health activities rose from 2% in 1989 to 5% in 2017, while interest in future global health experiences grew from 25% in 1989 to 32% in 2017. The study was published in Pediatrics.

Notable increases in global health participation were found in women (1% in 1989 to 5% in 2017) and men (3% in 1989 to 6% in 2017), subspecialists (3% in 1989 to 9% in 2017), and pediatricians who worked in medical school, hospital, or clinic settings (3% in 1989 to 8% in 2017).

In terms of age, pediatricians 50 years or older had a higher rate of a recent global health experience, with the largest increase in global health participation occurring in pediatricians 60 years and older (2% in 1989 to 9% in 2017), the study found.

Similarly, interest in future global health activities increased during the same time period for male and female pediatricians, for generalists and subspecialists, and for those working in medical school, hospital, or clinic settings. Clinical care and teaching settings were the most common preferences for future global health experiences in both 1989 and 2017. Administration and research were the least likely selected preferences in both surveys. Pediatricians affiliated with an academic institution, hospital, or clinic were more likely to have recently engaged in a global health activity and also were more likely express interest in such an opportunity, compared with solo pediatricians or those in small practices.

In an editorial accompanying the article, Suzinne Pak-Gorstein, MD, MPH, PhD, of the University of Washington, Seattle, said that the study highlights the importance of preparation for pediatricians who seek global health opportunities, particularly experiences that are short term.

“Ethical approaches to international work should be thoughtful and intentional, such as deciding to work with organizations that offer short-term experiences only in the context of long-term partnerships, considering the burden on local partners for hosting visitors, and insisting on a commitment to equitable collaborations that are mutually beneficial,” she wrote.

Dr. Pak-Gorstein added that future innovations in global health education can inspire learning experiences for pediatricians that utilize their passion and enthusiasm, while also enabling them to become more globally minded.

“In this way, pediatricians can be empowered to understand the world’s daunting challenges; respect cultural, religious, and socioeconomic differences; and facilitate dialogue and solutions for improving child health worldwide,” she concluded.

The survey was funded by the American Academy of Pediatrics. The study authors had no relevant financial disclosures. Dr. Pak-Gorstein said she received no funding for the editorial and had no relevant financial disclosures.

[email protected]

SOURCE: Chan K et al. Pediatrics. 2019 Dec 10. doi: 10.1542/peds.2019-1655.