MDedge Rheumatology

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

Johnson & Johnson (J&J) on Wednesday said it advanced into phase 3 testing of its COVID-19 vaccine candidate, which uses the same technology as an Ebola vaccine already approved by European regulators.

The National Institute of Allergy and Infectious Diseases, which is aiding Johnson & Johnson with development, described this in a news release as the fourth phase 3 clinical trial of evaluating an investigational vaccine for coronavirus disease.

This NIAID tally tracks products likely to be presented soon for Food and Drug Administration approval. (The World Health Organization’s COVID vaccine tracker lists nine candidates as having reached this stage, including products developed in Russia and China.)

As many as 60,000 volunteers will be enrolled in the trial, with about 215 clinical research sites expected to participate, NIAID said. The vaccine will be tested in the United States and abroad.

The start of this test, known as the ENSEMBLE trial, follows positive results from a Phase 1/2a clinical study, which involved a single vaccination. The results of this study have been submitted to medRxiv and are set to be published online imminently.

New Brunswick, N.J–based J&J said it intends to offer the vaccine on “a not-for-profit basis for emergency pandemic use.” If testing proceeds well, J&J might seek an emergency use clearance for the vaccine, which could possibly allow the first batches to be made available in early 2021.

J&J’s vaccine is unusual in that it will be tested based on a single dose, while other advanced candidates have been tested in two-dose regimens.

J&J on Wednesday also released the study protocol for its phase 3 test. The developers of the other late-stage COVID vaccine candidates also have done this, as reported by Medscape Medical News. Because of the great interest in the COVID vaccine, the American Medical Association had last month asked the FDA to keep physicians informed of their COVID-19 vaccine review process.
 

Trials and tribulations

One of these experimental COVID vaccines already has had a setback in phase 3 testing, which is a fairly routine occurrence in drug development. But with a pandemic still causing deaths and disrupting lives around the world, there has been intense interest in each step of the effort to develop a COVID vaccine.

AstraZeneca PLC earlier this month announced a temporary cessation of all their coronavirus vaccine trials to investigate an “unexplained illness” that arose in a participant, as reported by Medscape Medical News.

On September 12, AstraZeneca announced that clinical trials for the AZD1222, which it developed with Oxford University, had resumed in the United Kingdom. On Wednesday, CNBC said Health and Human Services Secretary Alex Azar told the news station that AstraZeneca’s late-stage coronavirus vaccine trial in the United States remains on hold until safety concerns are resolved, a critical issue with all the fast-track COVID vaccines now being tested.

“Look at the AstraZeneca program, phase 3 clinical trial, a lot of hope. [A] single serious adverse event report in the United Kingdom, global shutdown, and [a] hold of the clinical trials,” Mr. Azar told CNBC.

The New York Times has reported on concerns stemming from serious neurologic illnesses in two participants, both women, who received AstraZeneca’s experimental vaccine in Britain.

The Senate Health, Education, Labor and Pensions Committee on Wednesday separately held a hearing with the leaders of the FDA and the Centers of Disease Control and Prevention, allowing an airing of lawmakers’ concerns about a potential rush to approve a COVID vaccine.
 

Details of J&J trial

The J&J trial is designed primarily to determine if the investigational vaccine can prevent moderate to severe COVID-19 after a single dose. It also is designed to examine whether the vaccine can prevent COVID-19 requiring medical intervention and if the vaccine can prevent milder cases of COVID-19 and asymptomatic SARS-CoV-2 infection, NIAID said.

Principal investigators for the phase 3 trial of the J & J vaccine are Paul A. Goepfert, MD, director of the Alabama Vaccine Research Clinic at the University of Alabama in Birmingham; Beatriz Grinsztejn, MD, PhD, director of the Laboratory of Clinical Research on HIV/AIDS at the Evandro Chagas National Institute of Infectious Diseases-Oswaldo Cruz Foundation in Rio de Janeiro, Brazil; and Glenda E. Gray, MBBCh, president and chief executive officer of the South African Medical Research Council and coprincipal investigator of the HIV Vaccine Trials Network.

This article first appeared on Medscape.com.

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

A version of this article originally appeared on Medscape.com.

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

A version of this article originally appeared on Medscape.com.

States have begun preparing to distribute a COVID-19 vaccine if one is approved, a CDC official said today.

The CDC released guidance for states on Sept. 16 titled COVID-19 Vaccination Program Interim Playbook for Jurisdiction Operations. The document discusses vaccine ordering, storage, and handling and says that states should submit their plans for vaccine distribution to the agency by Oct. 16.

“Every jurisdiction is heavily involved right now in their plan development,” CDC official Janell Routh, MD, told the Advisory Committee on Immunization Practices during its Sept. 22 meeting. “It was really impressive to me that, even though the playbook only went out last week, states and jurisdictions have been thinking about this for quite some time.”

However, one committee member suggested that setting a deadline before more safety, efficacy, and storage information is known may be premature.

“I cannot imagine that we will actually know the final storage requirements for this vaccine by Oct. 16, which makes me a little concerned about finalizing state plans,” said Helen “Keipp” Talbot, MD, MPH, associate professor of medicine at Vanderbilt University Medical Center in Nashville, Tenn. “We also don’t know the best populations yet when it comes to efficacy and safety.”

Dr. Routh said the CDC is asking states to plan on the basis of assumptions. “We know those plans will constantly be improving, changing, as we learn more information,” Dr. Routh said. States agreed to return a plan 30 days after the playbook was released, which is how the Oct. 16 deadline was established, she said.

States are encouraged to think broadly. Plans may include contingencies for a product that requires ultracold storage or for distributing more than one vaccine product, Dr. Routh said.

“One goal is to be ready on the first day that we can actually distribute vaccine,” Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases, said during the meeting. “Our colleagues in Operation Warp Speed say that they expect there will be vaccine as early as November, and therefore we need to be ready so there is no delay in distributing that vaccine. And that phase, that early phase, is really close upon us.”

Many states have already developed plans, and the CDC is providing technical assistance as needed to monitor the plans regularly, Dr. Routh said.
 

Key issues identified

From holding pilot meetings with five jurisdictions, officials learned that public confidence in the vaccine is among states’ greatest concerns, Dr. Routh said. In addition, distribution is resource intensive, and social distancing adds logistical complexity.

Specific guidance on whom to vaccinate in the early stages will smooth the process, officials suggested during the pilot meetings. For the first several weeks, vaccine doses may be limited to priority populations, such as health care workers.

“This interim playbook is a living document,” Dr. Routh emphasized. “We definitely plan to update the content regularly as we learn more information about what vaccines and when they will be released.”

During the early stages of COVID-19 vaccination, officials plan to implement an enhanced monitoring program in which vaccine recipients would complete surveys about adverse events, in addition to the traditional vaccine safety monitoring programs that already exist, officials said.
 

A version of this article originally appeared on Medscape.com.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

Monitor antidrug antibodies for their impact on drug clearance to maximize treatment outcomes in rheumatology patients treated with biologics, Niels Vande Casteele, PharmD, PhD, said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Antidrug antibodies (ADAb) are associated with impaired drug efficacy and safety, he noted. Furthermore, he indicated that when ADAb bind to the drug, they can either block the activity of the drug directly and/or may cause the formation of complexes, leading to accelerated drug clearance and reduced drug exposure.

Dr. Vande Casteele, assistant professor in the department of medicine at the University of California, San Diego, outlined factors that contribute to immunogenicity, which occurs when the body reacts to neoantigens, or when there is a breakdown in immune tolerance, he said.

Genetics can play a key role in the risk for immunogenicity, as can the route of administration, dose, treatment duration, and concomitant diseases or medications, he explained.

In addition, product-related factors including sequence variation, glycosylation, host cells, contaminants and processing impurities, formulation, and handling and storage issues can impact immunogenicity, he noted.

For example, Dr. Vande Casteele cited a study in which the proportion of infliximab-treated patients with positive ADAbs was substantially higher among those receiving the drug intravenously, compared with those receiving it subcutaneously. As for treatment dosing, data on patients treated with infliximab have shown that maintenance therapy is associated with lower rates of immunogenicity, compared to episodic therapy, he said.

In terms of genetics, Dr. Vande Casteele cited a study published in January in Gastroenterology showing the presence of the HLA-DQA1*05 allele, carried by approximately 40% of the European population, significantly increased the rate of immunogenicity to infliximab and adalimumab in patients with Crohn’s disease (hazard ratio, 1.90).
 

Therapeutic drug monitoring and overcoming immunogenicity

Dr. Vande Casteele also reviewed how to measure ADAbs. “Antidrug antibody units and concentrations can differ across assays,” he said.

In clinical practice, “the majority of patients at the time of secondary loss of response will present with low drug exposure, and that is when you measure antidrug antibodies,” he said.

In rheumatology patients, the presence of ADAbs against anti–tumor necrosis factor monoclonal antibodies conveys a risk for treatment discontinuation, as well as “a risk of development of hypersensitivity reactions in all immune-mediated inflammatory diseases,” Dr. Vande Casteele said.

However, “the combined use of anti–tumor necrosis factor monoclonal antibodies and disease-modifying antirheumatic drugs reduces the development of antibodies and subsequent risks,” he noted.

For therapeutic drug monitoring in patients with a secondary loss of response, “first, look at the trough concentration,” Dr. Vande Casteele said. “If it is optimal, then ADAbs are probably inconsequential.” If the trough is low or undetectable, examine ADAbs, he added. To manage ADAbs, data support the use of drug dose escalation in some cases. However, “you may be able to overcome the antidrug antibodies in some patients with dose escalation, but this is not always a cost-effective strategy in the long term,” and some patients fail a drug despite adequate drug concentration, which may mean they are failing the mechanism, and not because of pharmacokinetic-related issues, he said.

Dr. Vande Casteele cited a post hoc analysis of the TAXIT trial, published in Gastroenterology. It was the first prospective study to look at proactive therapeutic drug monitoring in patients with inflammatory bowel diseases treated with maintenance infliximab. This post hoc analysis showed that ADAbs were overcome with dose escalation in nearly 50% of patients in the lowest two ADAb quartiles at the start of the trial, and although ADAb were masked by dose escalation in the highest two quartiles, measurement with a drug-sensitive assay showed that ADAb never disappeared, he said.

Another strategy to try to overcome immunogenicity is to add an immunomodulator, Dr. Vande Casteele said. He cited a recent study published in Rheumatology showing that the effect of methotrexate was mediated through immunogenicity for immunogenic compounds such as adalimumab.

Importantly, there is a risk for immunogenicity across agents, he noted. “Patients who are antibody positive to the prior anti-TNF are at a higher risk of developing antibodies to subsequent anti-TNFs.”

Dr. Vande Casteele reported receiving research grants from R-Biopharm; grants and personal fees from Takeda and UCB; and personal fees from Alimentiv (formerly Robarts Clinical Trials), Celltrion, and Prometheus. Global Academy for Medical Education and this news organization are owned by the same parent company.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

The companies behind three major COVID-19 vaccines in development released the protocols of their trials, outlining their expectations for participant enrollment, benchmarks for vaccine efficacy, and more details about the makeup of each product.

Typically, manufacturers guard the specifics of preclinical vaccine trials. This rare move follows calls for greater transparency. For example, the American Medical Association wrote a letter in late August asking the Food and Drug Administration to keep physicians informed of their COVID-19 vaccine review process.

On September 17, ModernaTx released the phase 3 trial protocol for its mRNA-1273 SARS-CoV-2 vaccine. In short order, on September 19, Pfizer/BioNTech shared their phase 1/2/3 trial vaccine protocol. AstraZeneca, which is developing a vaccine along with Oxford University, also released its protocol.

The AstraZeneca vaccine trial made headlines recently for having to be temporarily halted because of unexpected illnesses that arose in two participants, according to the New York Times and other sources.

“I applaud the release of the clinical trial protocols by the companies. The public trust in any COVID-19 vaccine is paramount, especially given the fast timeline and perceived political pressures of these candidates,” Robert Kruse, MD, PhD, told Medscape Medical News when asked to comment.
 

AstraZeneca takes a shot at transparency

The three primary objectives of the AstraZeneca AZD1222 trial outlined in the 110-page protocol include estimating the efficacy, safety, tolerability, and reactogenicity associated with two intramuscular doses of the vaccine in comparison with placebo in adults.

The projected enrollment is 30,000 participants, and the estimated primary completion date is Dec. 2, 2020, according to information on clinicaltrials.gov.

“Given the unprecedented global impact of the coronavirus pandemic and the need for public information, AstraZeneca has published the detailed protocol and design of our AZD1222 clinical trial,” the company said in a statement. “As with most clinical development, protocols are not typically shared publicly due to the importance of maintaining confidentiality and integrity of trials.

“AstraZeneca continues to work with industry peers to ensure a consistent approach to sharing timely clinical trial information,” the company added.
 

Moderna methodology

The ModernaTX 135-page protocol outlines the primary trial objectives of evaluating efficacy, safety, and reactogenicity of two injections of the vaccine administered 28 days apart. Researchers also plan to randomly assign 30,000 adults to receive either vaccine or placebo. The estimated primary completion date is Oct. 27, 2022.

A statement that was requested from ModernaTX was not received by press time.
 

Pfizer protocol

In the Pfizer/BioNTech vaccine trial, researchers plan to evaluate different doses in different age groups in a multistep protocol. The trial features 20 primary safety objectives, which include reporting adverse events and serious adverse events, including any local or systemic events.

Efficacy endpoints are secondary objectives. The estimated enrollment is 29,481 adults; the estimated primary completion date is April 19, 2021.

“Pfizer and BioNTech recognize that the COVID-19 pandemic is a unique circumstance, and the need for transparency is clear,” Pfizer spokesperson Sharon Castillo told Medscape Medical News. By making the full protocol available, “we believe this will reinforce our long-standing commitment to scientific and regulatory rigor that benefits patients,” she said.

“Based on current infection rates, Pfizer and BioNTech continue to expect that a conclusive read-out on efficacy is likely by the end of October. Neither Pfizer nor the FDA can move faster than the data we are generating through our clinical trial,” Castillo said.

If clinical work and regulatory approval or authorization proceed as planned, Pfizer and BioNTech expect to supply up to 100 million doses worldwide by the end of 2020 and approximately 1.3 billion doses worldwide by the end of 2021.

Pfizer is not willing to sacrifice safety and efficacy in the name of expediency, Castillo said. “We will not cut corners in this pursuit. Patient safety is our highest priority, and Pfizer will not bring a vaccine to market without adequate evidence of safety and efficacy.”
 

A positive move

“COVID-19 vaccines will only be useful if many people are willing to receive them,” said Kruse, a postgraduate year 3 resident in the Department of Pathology at Johns Hopkins Medicine in Baltimore, Maryland.

“By giving the general public along with other scientists and physicians the opportunity to critique the protocols, everyone can understand what the metrics would be for an early look at efficacy,” Kruse said. He noted that information could help inform a potential FDA emergency use authorization.

Kruse has disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

Hurricane Sally recently crossed the Gulf of Mexico and landed with torrential rainfalls along the Alabama coast. A little rainfall is important for crops; too much leads to devastation. As physicians, we need data in order to help manage patients’ illnesses and to help to keep them healthy. Our fear though is that too much data provided too quickly may have the opposite effect.

Personal monitoring devices

When I bought my first Fitbit 7 years ago, I was enamored with the technology. The Fitbit was little more than a step tracker, yet I proudly wore its black rubber strap on my wrist. It was my first foray into wearable technology, and it felt quite empowering to have an objective way to track my fitness beyond just using my bathroom scale. Now less than a decade later, that Fitbit looks archaic in comparison with the wrist-top technology currently available.

As I write this, the world’s largest technology company is in the process of releasing its sixth-generation Apple Watch. In addition to acting as a smartphone, this new device, which is barely larger than a postage stamp, offers GPS-based movement tracking, the ability to detect falls, continuous heart rate monitoring, a built-in EKG capable of diagnosing atrial fibrillation, and an oxygen saturation sensor. These features weren’t added thoughtlessly. Apple is marketing this as a health-focused device, with their primary advertising campaign claiming that “the future of health is on your wrist,” and they aren’t the only company making this play.

Along with Apple, Samsung, Withings, Fitbit, and other companies continue to bring products to market that monitor our activity and provide new insights into our health. Typically linked to smartphone-based apps, these devices record all of their measurements for later review, while software helps interpret the findings to make them actionable. From heart rate tracking to sleep analysis, these options now provide access to volumes of data that promise to improve our wellness and change our lives. Of course, those promises will only be fulfilled if our behavior is altered as a consequence of having more detailed information. Whether that will happen remains to be seen.
 

Health system–linked devices

Major advancements in medical monitoring technology are now enabling physicians to get much deeper insight into their patients’ health status. Internet-connected scales, blood pressure cuffs, and exercise equipment offer the ability to upload information into patient portals and integrate that information into EHRs. New devices provide access to information that previously was impossible to obtain. For example, wearable continuous blood glucose monitors, such as the FreeStyle Libre or DexCom’s G6, allow patients and physicians to follow blood sugar readings 24 hours a day. This provides unprecedented awareness of diabetes control and relieves the pain and inconvenience of finger sticks and blood draws. It also aids with compliance because patients don’t need to remember to check their sugar levels on a schedule.

Other compliance-boosting breakthroughs, such as Bluetooth-enabled asthma inhalers and cellular-connected continuous positive airway pressure machines, assist patients with managing chronic respiratory conditions. Many companies are developing technologies to manage acute conditions as well. One such company, an on-demand telemedicine provider called TytoCare, has developed a $299 suite of instruments that includes a digital stethoscope, thermometer, and camera-based otoscope. In concert with a virtual visit, their providers can remotely use these tools to examine and assess sick individuals. This virtual “laying on of hands” may have sounded like science fiction and likely would have been rejected by patients just a few years ago. Now it is becoming commonplace and will soon be an expectation of many seeking care.

We as clinicians need to learn how best to adapt to the new world and integrate these new sources of health data into our practices. But if we are to be successful, everyone must acknowledge that this revolution in health care brings many challenges along with it. One of those is the deluge of data that connected devices provide.
 

Information overload

There is such a thing as “too much of a good thing.” Described by journalist David Shenk as “data smog” in his 1997 book of the same name, the idea is clear: There is only so much information we can assimilate.

Even after years of using EHRs and with government-implemented incentives that promote “meaningful use,” physicians are still struggling with EHRs. Additionally, many have expressed frustration with the connectedness that EHRs provide and lament their inability to ever really “leave the office.” As more and more data become available to physicians, the challenge of how to assimilate and act on those data will continue to grow. The addition of patient-provided health statistics will only make information overload worse, with clinicians will feeling an ever-growing burden to know, understand, and act on this information.

Unless we develop systems to sort, filter, and prioritize the flow of information, there is potential for liability from not acting on the amount of virtual information doctors receive. This new risk for already fatigued and overburdened physicians combined with an increase in the amount of virtual information at doctors’ fingertips may lead to the value of patient data being lost.
 

Dr. Notte is a family physician and chief medical officer of Abington (Pa.) Hospital–Jefferson Health. Follow him on Twitter (@doctornotte). Dr. Skolnik is professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington Hospital–Jefferson Health. They have no conflicts related to the content of this piece.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has recommended approval of baricitinib tablets for adults with moderate to severe atopic dermatitis (AD) who are candidates for systemic therapy.

Baricitinib (Olumiant) is already approved in the European Union and the United States to treat moderate to severe active rheumatoid arthritis.

If approved in Europe, it will be the first Janus kinase (JAK) inhibitor and first oral medication indicated to treat patients with AD.

The CHMP’s positive opinion on baricitinib for AD was based on three phase 3, randomized, double-blind, placebo-controlled studies where the JAK inhibitor was used alone or in combination with topical treatments in adults with moderate to severe AD for whom topical treatments were insufficient or not tolerated. In all three studies, baricitinib was shown to be more effective than placebo in achieving skin that is “clear” or “almost clear” at 16 weeks.

“Patients living with AD face difficulties on a daily basis, and this CHMP opinion marks an important milestone in providing adult AD patients with a new potential treatment option,” Thomas Bieber, MD, PhD, professor of dermatology and allergy, University of Bonn (Germany), said in a company news release.

The most common side effects with baricitinib in clinical trials include increased LDL cholesterol, upper respiratory tract infections, and headache.

Patients receiving baricitinib, particularly in combination with immunosuppressants, are at risk of developing serious infections that may lead to hospitalization or death. If a serious infection develops, baricitinib should be stopped until the infection is controlled.

The CHMP’s positive opinion will be sent to the European Commission, which will adopt a final decision regarding an European Union–wide marketing authorization. Once granted, each member state will make decisions about price and reimbursement, taking into account the potential role/use of baricitinib in the context of that country’s national health system.

A version of this story originally appeared on Medscape.com.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

When it comes to preventing infection in rheumatology patients, “vaccination is the best mode of infection protection” and works synergistically with masks and hand washing, according to Leonard H. Calabrese, DO.

“Patients with rheumatic diseases have increased morbidity and mortality [from infection] and a lot of risk factors, including age, comorbidities, cytopenias, and extra-articular disease immunosuppression,” he said in a virtual presentation at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education.

Unfortunately, vaccination uptake remains “much lower than we would like in this country,” he said. Notably, influenza vaccination remains well below the World Health Organization target of 75%, he said.
 

Influenza vaccination

Flu vaccination will be even more important this year in the context of the COVID-19 pandemic, said Dr. Calabrese, professor of medicine and the RJ Fasenmyer Chair of Clinical Immunology at the Cleveland Clinic in Ohio. “For everyone who comes in with a respiratory illness, we will have to figure out whether it is flu or COVID,” he emphasized.

The Centers for Disease Control and Prevention recommendations include a detailed special considerations section for patients with immunocompromising conditions; “the notes have everything you need to know” about advising rheumatology patients, most of whom can safely receive a flu vaccine, he said.

One concern that always comes up is whether an antibody response will be suppressed based on therapy, Dr. Calabrese noted. Two major drugs with the greatest ability to reduce response are methotrexate and rituximab, he said. His tip: “Withhold methotrexate for two doses following seasonal flu vaccination.” This advice stems from a series of “practice-changing” studies by Park et al. published in 2017, 2018, and 2019 that showed benefit in withholding methotrexate for two doses following vaccination.

In the past, high-dose trivalent flu vaccines have been more expensive, and not necessarily practice changing, with studies showing varying clinical effectiveness and cost-effectiveness, Dr. Calabrese said. This year, a high-dose quadrivalent vaccine should be available that showed a 24% improvement in protection from all strains of influenza, compared with the standard vaccine in a head-to-head, randomized, controlled trial, he noted.

“All patients in rheumatology practices should get a flu vaccine,” with a 2-week hold on methotrexate following vaccination, he advised, and those aged 65 years and older should receive the high-dose quadrivalent. Younger patients on immunosuppressive therapy also might be considered for the high-dose vaccine, he said.

Pneumococcal vaccination

Dr. Calabrese also emphasized the value of pneumococcal vaccines for rheumatology patients. “The mortality for invasive disease ranges from 5% to 32%, but patients with immunocompromising conditions are at increased risk.”

Dr. Calabrese added a note on safety: Patients with cryopyrin-associated periodic syndrome (CAPS), a rare hereditary inflammatory disorder with cutaneous, neurologic, ophthalmologic, and rheumatologic manifestations, may have severe local and systemic reactions to the 23-valent polysaccharide vaccine (PPSV23), he said.

However, immunization against pneumococcal disease is safe and effective for most patients with autoimmune and inflammatory disorders regardless of their current therapy, he said. As with influenza, the CDC’s vaccination recommendations provide details for special situations, including immunocompromised individuals, he noted.

Dr. Calabrese recommended the 13-valent pneumococcal conjugate vaccine (PCV13) as soon as possible for rheumatology patients who have never been vaccinated, with follow-up doses of the 23-valent polysaccharide vaccine (PPSV23) at least 8 weeks later, and a PPSV23 booster 5 years after the first PPSV23 dose.
 

Protecting against shingles

When it comes to managing the varicella zoster virus (VZV) in immunocompromised patients, “prevention is preferable to treatment, as our patients are particularly vulnerable because of age and declining immunity,” Dr. Calabrese said.

Prevention is important because “once herpes zoster develops, the available treatments, including antiviral therapy, do not prevent postherpetic neuralgia in all patients,” he emphasized. “The treatments are complicated and not always effective,” he added.

The complications of zoster are well known, but recent data show an increased risk of cardiovascular disease as well, Dr. Calabrese said. “All the more reason to protect rheumatology patients from incident zoster,” he said.

Currently, the nonlive recombinant subunit zoster vaccine (Shingrix) is the preferred option for VZV vaccination according to the CDC’s Advisory Committee on Immunization Practices, Dr. Calabrese said. The CDC initially recommended its use to prevent herpes zoster and related complications in all immunocompetent adults aged 50 years and older; in an update, a C-level recommendation extends to “all patients aged 50 with or without immunosuppressive illnesses regardless of previous Zostavax exposure,” Dr. Calabrese said. “All patients on or starting [Janus] kinase inhibitors, regardless of age, should be considered” to receive the herpes zoster vaccine, he noted.

In general, promoting vaccination for rheumatology patients and for all patients is a multipronged effort that might include reminders, rewards, education, and standing orders, Dr. Calabrese said. Clinicians must continue to educate patients not only by strongly recommending the appropriate vaccines, but dispelling myths about vaccination, addressing fears, and providing current and accurate information, he said.

Dr. Calabrese disclosed relationships with AbbVie, Bristol-Myers Squibb, Crescendo, Genentech, Gilead, GlaxoSmithKline, Janssen, Novartis, Pfizer, Sanofi-Regeneron, and UCB.

Global Academy for Medical Education and this news organization are owned by the same parent company.

More female physicians are becoming specialists, a Medscape survey finds, and five specialties have seen particularly large increases during the last 5 years.

kate_sept2004/E+

Obstetrician/gynecologists and pediatricians had the largest female representation at 58% and those percentages were both up from 50% in 2015, according to the Medscape Female Physician Compensation Report 2020.

Rheumatology saw a dramatic jump in numbers of women from 29% in 2015 to 54% now. Dermatology increased from 32% to 49%, and family medicine rose from 35% to 43% during that time.
 

Specialist pay gap narrows slightly

As in the past 10 years of the survey, female physicians continue to make less than their male colleagues. The gender gap was the same this year in primary care — women made 25% less ($212,000 vs. $264,000).

The gap in specialists narrowed slightly. Women made 31% less this year ($286,000 vs $375,000) instead of the 33% less reported in last year’s survey, a difference of $89,000 this year.

The gender pay gap was consistent across all race and age groups and was consistent in responses about net worth. Whereas 57% of male physicians had a net worth of $1 million or more, only 40% of female physicians did. Twice as many male physicians as female physicians had a net worth of more than $5 million (10% vs. 5%).

“Many physicians expect the gender pay gap to narrow in the coming years,” John Prescott, MD, chief academic officer of the Association of American Medical Colleges, said in an interview.

“Yet, it is a challenging task, requiring an institutional commitment to transparency, cross-campus collaboration, ongoing communication, dedicated resources, and enlightened leadership,” he said.

Female physicians working in office-based, solo practices made the most overall at $290,000; women in outpatient settings made the least at $223,000.

The survey included more than 4,500 responses. The responses were collected during the early part of the year and do not reflect changes in income expected from the COVID-19 pandemic.

An analysis in Health Affairs, for instance, predicted that primary care practices would lose $67,774 in gross revenue per full-time-equivalent physician in calendar year 2020 because of the pandemic.

Most physicians did not experience a significant financial loss in 2019, but COVID-19 may, at least temporarily, change those answers in next year’s report, physicians predicted.
 

Women more likely than men to live above their means

More women this year (39%) said they live below their means than answered that way last year (31%). Female physicians were more likely to say they lived above their means than were their male counterparts (8% vs. 6%).

Greenwald Wealth Management in St. Louis Park, Minn., says aiming for putting away 20% of total gross salary is a good financial goal.

Women in this year’s survey spent about 7% less time seeing patients than did their male counterparts (35.9 hours a week vs. 38.8). The average for all physicians was 37.8 hours a week. Add the 15.6 average hours per week physicians spend on paperwork, and they are putting in 53-hour workweeks on average overall.

Asked what parts of their job they found most rewarding, women were more likely than were men to say “gratitude/relationships with patients” (31% vs. 25%). They were less likely than were men to answer that the most rewarding part was “being very good at what I do/finding answers/diagnoses” (22% vs. 25%) or “making good money at a job I like” (9% vs. 13%).

Most female physicians — and physicians overall — said they would choose medicine again. But two specialties saw a substantial increase in that answer.

This year, 79% of those in physical medicine and rehabilitation said they would choose medicine again (compared with 66% last year) and 84% of gastroenterologists answered that way (compared with 76% in 2019).

Psychiatrists, however, were in the group least likely to say they would choose their specialty again along with those in internal medicine, family medicine, and diabetes and endocrinology.

Female physicians in orthopedics, radiology, and dermatology were most likely to choose their specialties again (91% - 92%).

Female physicians were less likely to use physician assistants in their practices than were their male colleagues (31% vs. 38%) but more likely to use NPs (52% vs. 50%). More than a third (38%) of male and female physicians reported they use neither.
 

A version of this article originally appeared on Medscape.com.

More female physicians are becoming specialists, a Medscape survey finds, and five specialties have seen particularly large increases during the last 5 years.

kate_sept2004/E+

Obstetrician/gynecologists and pediatricians had the largest female representation at 58% and those percentages were both up from 50% in 2015, according to the Medscape Female Physician Compensation Report 2020.

Rheumatology saw a dramatic jump in numbers of women from 29% in 2015 to 54% now. Dermatology increased from 32% to 49%, and family medicine rose from 35% to 43% during that time.
 

Specialist pay gap narrows slightly

As in the past 10 years of the survey, female physicians continue to make less than their male colleagues. The gender gap was the same this year in primary care — women made 25% less ($212,000 vs. $264,000).

The gap in specialists narrowed slightly. Women made 31% less this year ($286,000 vs $375,000) instead of the 33% less reported in last year’s survey, a difference of $89,000 this year.

The gender pay gap was consistent across all race and age groups and was consistent in responses about net worth. Whereas 57% of male physicians had a net worth of $1 million or more, only 40% of female physicians did. Twice as many male physicians as female physicians had a net worth of more than $5 million (10% vs. 5%).

“Many physicians expect the gender pay gap to narrow in the coming years,” John Prescott, MD, chief academic officer of the Association of American Medical Colleges, said in an interview.

“Yet, it is a challenging task, requiring an institutional commitment to transparency, cross-campus collaboration, ongoing communication, dedicated resources, and enlightened leadership,” he said.

Female physicians working in office-based, solo practices made the most overall at $290,000; women in outpatient settings made the least at $223,000.

The survey included more than 4,500 responses. The responses were collected during the early part of the year and do not reflect changes in income expected from the COVID-19 pandemic.

An analysis in Health Affairs, for instance, predicted that primary care practices would lose $67,774 in gross revenue per full-time-equivalent physician in calendar year 2020 because of the pandemic.

Most physicians did not experience a significant financial loss in 2019, but COVID-19 may, at least temporarily, change those answers in next year’s report, physicians predicted.
 

Women more likely than men to live above their means

More women this year (39%) said they live below their means than answered that way last year (31%). Female physicians were more likely to say they lived above their means than were their male counterparts (8% vs. 6%).

Greenwald Wealth Management in St. Louis Park, Minn., says aiming for putting away 20% of total gross salary is a good financial goal.

Women in this year’s survey spent about 7% less time seeing patients than did their male counterparts (35.9 hours a week vs. 38.8). The average for all physicians was 37.8 hours a week. Add the 15.6 average hours per week physicians spend on paperwork, and they are putting in 53-hour workweeks on average overall.

Asked what parts of their job they found most rewarding, women were more likely than were men to say “gratitude/relationships with patients” (31% vs. 25%). They were less likely than were men to answer that the most rewarding part was “being very good at what I do/finding answers/diagnoses” (22% vs. 25%) or “making good money at a job I like” (9% vs. 13%).

Most female physicians — and physicians overall — said they would choose medicine again. But two specialties saw a substantial increase in that answer.

This year, 79% of those in physical medicine and rehabilitation said they would choose medicine again (compared with 66% last year) and 84% of gastroenterologists answered that way (compared with 76% in 2019).

Psychiatrists, however, were in the group least likely to say they would choose their specialty again along with those in internal medicine, family medicine, and diabetes and endocrinology.

Female physicians in orthopedics, radiology, and dermatology were most likely to choose their specialties again (91% - 92%).

Female physicians were less likely to use physician assistants in their practices than were their male colleagues (31% vs. 38%) but more likely to use NPs (52% vs. 50%). More than a third (38%) of male and female physicians reported they use neither.
 

A version of this article originally appeared on Medscape.com.

More female physicians are becoming specialists, a Medscape survey finds, and five specialties have seen particularly large increases during the last 5 years.

kate_sept2004/E+

Obstetrician/gynecologists and pediatricians had the largest female representation at 58% and those percentages were both up from 50% in 2015, according to the Medscape Female Physician Compensation Report 2020.

Rheumatology saw a dramatic jump in numbers of women from 29% in 2015 to 54% now. Dermatology increased from 32% to 49%, and family medicine rose from 35% to 43% during that time.
 

Specialist pay gap narrows slightly

As in the past 10 years of the survey, female physicians continue to make less than their male colleagues. The gender gap was the same this year in primary care — women made 25% less ($212,000 vs. $264,000).

The gap in specialists narrowed slightly. Women made 31% less this year ($286,000 vs $375,000) instead of the 33% less reported in last year’s survey, a difference of $89,000 this year.

The gender pay gap was consistent across all race and age groups and was consistent in responses about net worth. Whereas 57% of male physicians had a net worth of $1 million or more, only 40% of female physicians did. Twice as many male physicians as female physicians had a net worth of more than $5 million (10% vs. 5%).

“Many physicians expect the gender pay gap to narrow in the coming years,” John Prescott, MD, chief academic officer of the Association of American Medical Colleges, said in an interview.

“Yet, it is a challenging task, requiring an institutional commitment to transparency, cross-campus collaboration, ongoing communication, dedicated resources, and enlightened leadership,” he said.

Female physicians working in office-based, solo practices made the most overall at $290,000; women in outpatient settings made the least at $223,000.

The survey included more than 4,500 responses. The responses were collected during the early part of the year and do not reflect changes in income expected from the COVID-19 pandemic.

An analysis in Health Affairs, for instance, predicted that primary care practices would lose $67,774 in gross revenue per full-time-equivalent physician in calendar year 2020 because of the pandemic.

Most physicians did not experience a significant financial loss in 2019, but COVID-19 may, at least temporarily, change those answers in next year’s report, physicians predicted.
 

Women more likely than men to live above their means

More women this year (39%) said they live below their means than answered that way last year (31%). Female physicians were more likely to say they lived above their means than were their male counterparts (8% vs. 6%).

Greenwald Wealth Management in St. Louis Park, Minn., says aiming for putting away 20% of total gross salary is a good financial goal.

Women in this year’s survey spent about 7% less time seeing patients than did their male counterparts (35.9 hours a week vs. 38.8). The average for all physicians was 37.8 hours a week. Add the 15.6 average hours per week physicians spend on paperwork, and they are putting in 53-hour workweeks on average overall.

Asked what parts of their job they found most rewarding, women were more likely than were men to say “gratitude/relationships with patients” (31% vs. 25%). They were less likely than were men to answer that the most rewarding part was “being very good at what I do/finding answers/diagnoses” (22% vs. 25%) or “making good money at a job I like” (9% vs. 13%).

Most female physicians — and physicians overall — said they would choose medicine again. But two specialties saw a substantial increase in that answer.

This year, 79% of those in physical medicine and rehabilitation said they would choose medicine again (compared with 66% last year) and 84% of gastroenterologists answered that way (compared with 76% in 2019).

Psychiatrists, however, were in the group least likely to say they would choose their specialty again along with those in internal medicine, family medicine, and diabetes and endocrinology.

Female physicians in orthopedics, radiology, and dermatology were most likely to choose their specialties again (91% - 92%).

Female physicians were less likely to use physician assistants in their practices than were their male colleagues (31% vs. 38%) but more likely to use NPs (52% vs. 50%). More than a third (38%) of male and female physicians reported they use neither.
 

A version of this article originally appeared on Medscape.com.

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the Food and Drug Administration and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.

It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.

If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.

The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.

Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.

“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”

Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.

Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.

After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.

“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.

White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.

Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”

Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.

Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.

Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.

The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”

Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.

Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.

Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.

AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.

Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.

“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”

In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”

But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.

Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.

Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.

A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.

“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.

Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”

In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.

But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.

Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the Food and Drug Administration and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.

It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.

If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.

The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.

Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.

“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”

Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.

Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.

After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.

“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.

White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.

Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”

Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.

Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.

Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.

The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”

Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.

Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.

Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.

AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.

Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.

“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”

In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”

But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.

Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.

Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.

A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.

“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.

Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”

In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.

But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.

Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

President Donald Trump, who seems intent on announcing a COVID-19 vaccine before Election Day, could legally authorize a vaccine over the objections of experts, officials at the Food and Drug Administration and even vaccine manufacturers, who have pledged not to release any vaccine unless it’s proved safe and effective.

In podcasts, public forums, social media and medical journals, a growing number of prominent health leaders say they fear that Mr. Trump – who has repeatedly signaled his desire for the swift approval of a vaccine and his displeasure with perceived delays at the FDA – will take matters into his own hands, running roughshod over the usual regulatory process.

It would reflect another attempt by a norm-breaking administration, poised to ram through a Supreme Court nominee opposed to existing abortion rights and the Affordable Care Act, to inject politics into sensitive public health decisions. Mr. Trump has repeatedly contradicted the advice of senior scientists on COVID-19 while pushing controversial treatments for the disease.

If the executive branch were to overrule the FDA’s scientific judgment, a vaccine of limited efficacy and, worse, unknown side effects could be rushed to market.

The worries intensified over the weekend, after Alex Azar, the administration’s secretary of Health & Human Services, asserted his agency’s rule-making authority over the FDA. HHS spokesperson Caitlin Oakley said Mr. Azar’s decision had no bearing on the vaccine approval process.

Vaccines are typically approved by the FDA. Alternatively, Mr. Azar – who reports directly to Mr. Trump – can issue an emergency use authorization, even before any vaccines have been shown to be safe and effective in late-stage clinical trials.

“Yes, this scenario is certainly possible legally and politically,” said Jerry Avorn, MD, a professor of medicine at Harvard Medical School, who outlined such an event in the New England Journal of Medicine. He said it “seems frighteningly more plausible each day.”

Vaccine experts and public health officials are particularly vexed by the possibility because it could ruin the fragile public confidence in a COVID-19 vaccine. It might put scientific authorities in the position of urging people not to be vaccinated after years of coaxing hesitant parents to ignore baseless fears.

Physicians might refuse to administer a vaccine approved with inadequate data, said Preeti Malani, MD, chief health officer and professor of medicine at the University of Michigan in Ann Arbor, in a recent webinar. “You could have a safe, effective vaccine that no one wants to take.” A recent KFF poll found that 54% of Americans would not submit to a COVID-19 vaccine authorized before Election Day.

After this story was published, an HHS official said that Mr. Azar “will defer completely to the FDA” as the agency weighs whether to approve a vaccine produced through the government’s Operation Warp Speed effort.

“The idea the Secretary would approve or authorize a vaccine over the FDA’s objections is preposterous and betrays ignorance of the transparent process that we’re following for the development of the OWS vaccines,” HHS chief of staff Brian Harrison wrote in an email.

White House spokesperson Judd Deere dismissed the scientists’ concerns, saying Trump cared only about the public’s safety and health. “This false narrative that the media and Democrats have created that politics is influencing approvals is not only false but is a danger to the American public,” he said.

Usually, the FDA approves vaccines only after companies submit years of data proving that a vaccine is safe and effective. But a 2004 law allows the FDA to issue an emergency use authorization with much less evidence, as long as the vaccine “may be effective” and its “known and potential benefits” outweigh its “known and potential risks.”

Many scientists doubt a vaccine could meet those criteria before the election. But the terms might be legally vague enough to allow the administration to take such steps.

Moncef Slaoui, chief scientific adviser to Operation Warp Speed, the government program aiming to more quickly develop COVID-19 vaccines, said it’s “extremely unlikely” that vaccine trial results will be ready before the end of October.

Mr. Trump, however, has insisted repeatedly that a vaccine to fight the pandemic that has claimed 200,000 American lives will be distributed starting next month. He reiterated that claim Saturday at a campaign rally in Fayetteville, N.C.

The vaccine will be ready “in a matter of weeks,” he said. “We will end the pandemic from China.”

Although pharmaceutical companies have launched three clinical trials in the United States, no one can say with certainty when those trials will have enough data to determine whether the vaccines are safe and effective.

Officials at Moderna, whose vaccine is being tested in 30,000 volunteers, have said their studies could produce a result by the end of the year, although the final analysis could take place next spring.

Pfizer executives, who have expanded their clinical trial to 44,000 participants, boast that they could know their vaccine works by the end of October.

AstraZeneca’s U.S. vaccine trial, which was scheduled to enroll 30,000 volunteers, is on hold pending an investigation of a possible vaccine-related illness.

Scientists have warned for months that the Trump administration could try to win the election with an “October surprise,” authorizing a vaccine that hasn’t been fully tested. “I don’t think people are crazy to be thinking about all of this,” said William Schultz, a partner in a Washington, D.C., law firm who served as a former FDA commissioner for policy and as general counsel for HHS.

“You’ve got a president saying you’ll have an approval in October. Everybody’s wondering how that could happen.”

In an opinion piece published in the Wall Street Journal, conservative former FDA commissioners Scott Gottlieb and Mark McClellan argued that presidential intrusion was unlikely because the FDA’s “thorough and transparent process doesn’t lend itself to meddling. Any deviation would quickly be apparent.”

But the administration has demonstrated a willingness to bend the agency to its will. The FDA has been criticized for issuing emergency authorizations for two COVID-19 treatments that were boosted by the president but lacked strong evidence to support them: hydroxychloroquine and convalescent plasma.

Mr. Azar has sidelined the FDA in other ways, such as by blocking the agency from regulating lab-developed tests, including tests for the novel coronavirus.

Although FDA Commissioner Stephen Hahn told the Financial Times he would be willing to approve emergency use of a vaccine before large-scale studies conclude, agency officials also have pledged to ensure the safety of any COVID-19 vaccines.

A senior FDA official who oversees vaccine approvals, Peter Marks, MD, has said he will quit if his agency rubber-stamps an unproven COVID-19 vaccine.

“I think there would be an outcry from the public health community second to none, which is my worst nightmare – my worst nightmare – because we will so confuse the public,” said Michael Osterholm, PhD, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, in his weekly podcast.

Still, “even if a company did not want it to be done, even if the FDA did not want it to be done, he could still do that,” said Dr. Osterholm, in his podcast. “I hope that we’d never see that happen, but we have to entertain that’s a possibility.”

In the New England Journal editorial, Dr. Avorn and coauthor Aaron Kesselheim, MD, wondered whether Mr. Trump might invoke the 1950 Defense Production Act to force reluctant drug companies to manufacture their vaccines.

But Mr. Trump would have to sue a company to enforce the Defense Production Act, and the company would have a strong case in refusing, said Lawrence Gostin, director of Georgetown’s O’Neill Institute for National and Global Health Law.

Also, he noted that Mr. Trump could not invoke the Defense Production Act unless a vaccine were “scientifically justified and approved by the FDA.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of KFF (Kaiser Family Foundation), which is not affiliated with Kaiser Permanente.

When an insurance coverage snafu threatened to take away a vital infusion drug for one of her patients, Julie Baak discovered that writing a letter wasn’t enough. Simponi Aria (golimumab) is the least expensive of all rheumatoid arthritis drugs for infusion, and at only six infusions a year offers a better experience for patients when compared with more expensive drugs like Humira (adalimumab), said Ms. Baak, practice manager at the Arthritis Center in St. Louis.

United Healthcare had drafted, then retracted, policy changes affecting and delaying access to RA drugs like Simponi Aria. Ms. Baak’s patient thrived on this drug after failing with others. UHC “kept pointing the finger at the employer, a self-funded plan,” she explained. Once correspondence efforts between the employer and payer fell through, she called a local news reporter, arranging an interview between Steven Baak, MD, the office’s medical director, and the patient, who was willing to go on the news. Through a 3-minute news segment, “we got that insurance company to allow us to get coverage for Simponi Aria on the medical side.”

Ms. Baak joined Karen Ferguson, Nilsa Cruz, and Madelaine A. Feldman, MD, at the Coalition of State Rheumatology Organizations 2020 State Society Advocacy Conference Virtual Meeting to discuss the power of advocacy in rheumatology, and impart strategies for enabling change. The Simponi Aria example underscores the importance of media and social media, Ms. Baak said. “When people do the wrong thing, you can bring light to others.”

The news spot on Dr. Baak and his patient mobilized Ms. Cruz to share it with others. “I took that interview and blasted it all over Wisconsin and to my colleagues because they needed to know what the options were for us in advocacy,” stressed Ms. Cruz, practice administrator of Milwaukee Rheumatology Center.

Rheumatologists are master problem solvers – the Sherlock Holmes’ of the medical industry, she continued. However, not many insurance companies understand the cognitive value of what they do. “There’s a lack of communication and education,” Ms. Cruz noted. Any advocacy measures calls for research on the topic, the panel stressed. It involves looking through medical and administrative insurance companies’ policies and using Google and social media, such as Twitter, to identify topics and key decision makers, a practice Ms. Cruz favors in particular.
 

Physicians as reliable sources

You need good documentation to support why you’re doing what you’re doing, advised Ms. Ferguson, practice administrator of Arthritis Northwest, Spokane, Wash. When an issue comes up, she always consults her doctors and her billing staff.

She recalled when biosimilars first came out, and one of them for Rituxan (rituximab) had not been indicated by the Food and Drug Administration for RA. “And yet, an insurance company was mandating that we use this nonindicated biosimilar,” said Ms. Ferguson, who learned about this from her billing staff. “I went immediately to the doctors and asked how they felt about this, and they said they were uncomfortable,” she continued. Ms. Ferguson found out that 45 states had legislation that prohibited interchangeability with non–FDA-indicated drugs. She was able to show this literature to the insurance company and get the mandate reversed. “One thing that’s so important is to be able to use your physicians’ knowledge and how they really feel and advocate based off of that,” using sound statutes to support your argument, she added.

“Ensuring that patients get the right medications that their physicians deem is important is critical for improved safety and efficacy,” Ms. Ferguson said. Yet, she acknowledged that facing off against an insurance company or a pharmacy benefit manager is often hard to do.

Many practices don’t have a Julie Baak or Karen Ferguson to fight on their behalf, Ms. Cruz noted. In this case, they should look within their state for high-profile advocates. “I guarantee you, every state has one. Practices should be able to reach out to those individuals, or respective state societies, or CSRO,” Ms. Cruz said. Best results are obtained when working through coalitions.
 

Patient testimony can make an impact

CSRO recently enacted a public relations campaign to shine a light on certain health plan policies that are harmful to patients. “We have been able to get the real impact of the policy on patients and their stories into the public eye,” Dr. Feldman, a rheumatologist in New Orleans and CSRO president, said in an interview. The group has spearheaded the effort to keep Stelara off of the Medicare self-administered drug list. CSRO has also built coalitions and provided testimony on several state step therapy and nonmedical switching bills. “When asked if these are pharma-backed bills, we say: ‘No, these are patient-backed bills,’ ” she added.

Patients act as powerful witnesses at hearings. “When legislation is being considered, it is important for both physicians and patients to be heard and to tell their stories,” Dr. Feldman said.

Ms. Cruz makes a point of getting involved with the payers themselves. As an example, she serves as a member on UHC’s National Steering Committee. “They know me to be very outspoken. Sometimes they listen, sometimes they don’t. Nevertheless, I consider it a compliment when they say they like that I hold them accountable. Every little thing that I can do to bring issues to the table,” filtering into their other divisions, is an accomplishment, she said.

When an insurance coverage snafu threatened to take away a vital infusion drug for one of her patients, Julie Baak discovered that writing a letter wasn’t enough. Simponi Aria (golimumab) is the least expensive of all rheumatoid arthritis drugs for infusion, and at only six infusions a year offers a better experience for patients when compared with more expensive drugs like Humira (adalimumab), said Ms. Baak, practice manager at the Arthritis Center in St. Louis.

United Healthcare had drafted, then retracted, policy changes affecting and delaying access to RA drugs like Simponi Aria. Ms. Baak’s patient thrived on this drug after failing with others. UHC “kept pointing the finger at the employer, a self-funded plan,” she explained. Once correspondence efforts between the employer and payer fell through, she called a local news reporter, arranging an interview between Steven Baak, MD, the office’s medical director, and the patient, who was willing to go on the news. Through a 3-minute news segment, “we got that insurance company to allow us to get coverage for Simponi Aria on the medical side.”

Ms. Baak joined Karen Ferguson, Nilsa Cruz, and Madelaine A. Feldman, MD, at the Coalition of State Rheumatology Organizations 2020 State Society Advocacy Conference Virtual Meeting to discuss the power of advocacy in rheumatology, and impart strategies for enabling change. The Simponi Aria example underscores the importance of media and social media, Ms. Baak said. “When people do the wrong thing, you can bring light to others.”

The news spot on Dr. Baak and his patient mobilized Ms. Cruz to share it with others. “I took that interview and blasted it all over Wisconsin and to my colleagues because they needed to know what the options were for us in advocacy,” stressed Ms. Cruz, practice administrator of Milwaukee Rheumatology Center.

Rheumatologists are master problem solvers – the Sherlock Holmes’ of the medical industry, she continued. However, not many insurance companies understand the cognitive value of what they do. “There’s a lack of communication and education,” Ms. Cruz noted. Any advocacy measures calls for research on the topic, the panel stressed. It involves looking through medical and administrative insurance companies’ policies and using Google and social media, such as Twitter, to identify topics and key decision makers, a practice Ms. Cruz favors in particular.
 

Physicians as reliable sources

You need good documentation to support why you’re doing what you’re doing, advised Ms. Ferguson, practice administrator of Arthritis Northwest, Spokane, Wash. When an issue comes up, she always consults her doctors and her billing staff.

She recalled when biosimilars first came out, and one of them for Rituxan (rituximab) had not been indicated by the Food and Drug Administration for RA. “And yet, an insurance company was mandating that we use this nonindicated biosimilar,” said Ms. Ferguson, who learned about this from her billing staff. “I went immediately to the doctors and asked how they felt about this, and they said they were uncomfortable,” she continued. Ms. Ferguson found out that 45 states had legislation that prohibited interchangeability with non–FDA-indicated drugs. She was able to show this literature to the insurance company and get the mandate reversed. “One thing that’s so important is to be able to use your physicians’ knowledge and how they really feel and advocate based off of that,” using sound statutes to support your argument, she added.

“Ensuring that patients get the right medications that their physicians deem is important is critical for improved safety and efficacy,” Ms. Ferguson said. Yet, she acknowledged that facing off against an insurance company or a pharmacy benefit manager is often hard to do.

Many practices don’t have a Julie Baak or Karen Ferguson to fight on their behalf, Ms. Cruz noted. In this case, they should look within their state for high-profile advocates. “I guarantee you, every state has one. Practices should be able to reach out to those individuals, or respective state societies, or CSRO,” Ms. Cruz said. Best results are obtained when working through coalitions.
 

Patient testimony can make an impact

CSRO recently enacted a public relations campaign to shine a light on certain health plan policies that are harmful to patients. “We have been able to get the real impact of the policy on patients and their stories into the public eye,” Dr. Feldman, a rheumatologist in New Orleans and CSRO president, said in an interview. The group has spearheaded the effort to keep Stelara off of the Medicare self-administered drug list. CSRO has also built coalitions and provided testimony on several state step therapy and nonmedical switching bills. “When asked if these are pharma-backed bills, we say: ‘No, these are patient-backed bills,’ ” she added.

Patients act as powerful witnesses at hearings. “When legislation is being considered, it is important for both physicians and patients to be heard and to tell their stories,” Dr. Feldman said.

Ms. Cruz makes a point of getting involved with the payers themselves. As an example, she serves as a member on UHC’s National Steering Committee. “They know me to be very outspoken. Sometimes they listen, sometimes they don’t. Nevertheless, I consider it a compliment when they say they like that I hold them accountable. Every little thing that I can do to bring issues to the table,” filtering into their other divisions, is an accomplishment, she said.

When an insurance coverage snafu threatened to take away a vital infusion drug for one of her patients, Julie Baak discovered that writing a letter wasn’t enough. Simponi Aria (golimumab) is the least expensive of all rheumatoid arthritis drugs for infusion, and at only six infusions a year offers a better experience for patients when compared with more expensive drugs like Humira (adalimumab), said Ms. Baak, practice manager at the Arthritis Center in St. Louis.

United Healthcare had drafted, then retracted, policy changes affecting and delaying access to RA drugs like Simponi Aria. Ms. Baak’s patient thrived on this drug after failing with others. UHC “kept pointing the finger at the employer, a self-funded plan,” she explained. Once correspondence efforts between the employer and payer fell through, she called a local news reporter, arranging an interview between Steven Baak, MD, the office’s medical director, and the patient, who was willing to go on the news. Through a 3-minute news segment, “we got that insurance company to allow us to get coverage for Simponi Aria on the medical side.”

Ms. Baak joined Karen Ferguson, Nilsa Cruz, and Madelaine A. Feldman, MD, at the Coalition of State Rheumatology Organizations 2020 State Society Advocacy Conference Virtual Meeting to discuss the power of advocacy in rheumatology, and impart strategies for enabling change. The Simponi Aria example underscores the importance of media and social media, Ms. Baak said. “When people do the wrong thing, you can bring light to others.”

The news spot on Dr. Baak and his patient mobilized Ms. Cruz to share it with others. “I took that interview and blasted it all over Wisconsin and to my colleagues because they needed to know what the options were for us in advocacy,” stressed Ms. Cruz, practice administrator of Milwaukee Rheumatology Center.

Rheumatologists are master problem solvers – the Sherlock Holmes’ of the medical industry, she continued. However, not many insurance companies understand the cognitive value of what they do. “There’s a lack of communication and education,” Ms. Cruz noted. Any advocacy measures calls for research on the topic, the panel stressed. It involves looking through medical and administrative insurance companies’ policies and using Google and social media, such as Twitter, to identify topics and key decision makers, a practice Ms. Cruz favors in particular.
 

Physicians as reliable sources

You need good documentation to support why you’re doing what you’re doing, advised Ms. Ferguson, practice administrator of Arthritis Northwest, Spokane, Wash. When an issue comes up, she always consults her doctors and her billing staff.

She recalled when biosimilars first came out, and one of them for Rituxan (rituximab) had not been indicated by the Food and Drug Administration for RA. “And yet, an insurance company was mandating that we use this nonindicated biosimilar,” said Ms. Ferguson, who learned about this from her billing staff. “I went immediately to the doctors and asked how they felt about this, and they said they were uncomfortable,” she continued. Ms. Ferguson found out that 45 states had legislation that prohibited interchangeability with non–FDA-indicated drugs. She was able to show this literature to the insurance company and get the mandate reversed. “One thing that’s so important is to be able to use your physicians’ knowledge and how they really feel and advocate based off of that,” using sound statutes to support your argument, she added.

“Ensuring that patients get the right medications that their physicians deem is important is critical for improved safety and efficacy,” Ms. Ferguson said. Yet, she acknowledged that facing off against an insurance company or a pharmacy benefit manager is often hard to do.

Many practices don’t have a Julie Baak or Karen Ferguson to fight on their behalf, Ms. Cruz noted. In this case, they should look within their state for high-profile advocates. “I guarantee you, every state has one. Practices should be able to reach out to those individuals, or respective state societies, or CSRO,” Ms. Cruz said. Best results are obtained when working through coalitions.
 

Patient testimony can make an impact

CSRO recently enacted a public relations campaign to shine a light on certain health plan policies that are harmful to patients. “We have been able to get the real impact of the policy on patients and their stories into the public eye,” Dr. Feldman, a rheumatologist in New Orleans and CSRO president, said in an interview. The group has spearheaded the effort to keep Stelara off of the Medicare self-administered drug list. CSRO has also built coalitions and provided testimony on several state step therapy and nonmedical switching bills. “When asked if these are pharma-backed bills, we say: ‘No, these are patient-backed bills,’ ” she added.

Patients act as powerful witnesses at hearings. “When legislation is being considered, it is important for both physicians and patients to be heard and to tell their stories,” Dr. Feldman said.

Ms. Cruz makes a point of getting involved with the payers themselves. As an example, she serves as a member on UHC’s National Steering Committee. “They know me to be very outspoken. Sometimes they listen, sometimes they don’t. Nevertheless, I consider it a compliment when they say they like that I hold them accountable. Every little thing that I can do to bring issues to the table,” filtering into their other divisions, is an accomplishment, she said.