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J&J’s one-shot COVID-19 vaccine advances to phase 3 testing
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.
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.
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.
What to do when a patient is not ready to stop smoking
Recommendations from the American Thoracic Society
Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.
Case
A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?
The Guideline in context
Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.1
In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.
This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.1 Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.2 This hypothesis was examined in five randomized trials.1
In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.1
Suggested treatment
This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.
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 (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.
References
1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.
2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.
Recommendations from the American Thoracic Society
Recommendations from the American Thoracic Society
Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.
Case
A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?
The Guideline in context
Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.1
In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.
This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.1 Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.2 This hypothesis was examined in five randomized trials.1
In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.1
Suggested treatment
This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.
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 (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.
References
1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.
2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.
Below is a case involving a patient who is not yet ready to quit smoking. We later provide treatment recommendations for this patient based on a new guideline from the American Thoracic Society.
Case
A 58-year-old female comes into the office for a physical exam. She has been smoking two packs a day since she was 23 years of age. You have tried at previous visits to get her to quit, but she hasn’t been interested. The patient says she has a lot of stress, and that it is still not the right time for her to stop smoking. You tell her she needs to quit and, though the patient understands that quitting would be beneficial for her health, she just isn’t ready to try to kick the habit. How do you proceed?
The Guideline in context
Even though this patient stated that she is not ready to stop smoking, she is still a candidate for pharmacological treatment for her tobacco dependence and can be offered varenicline, according to the ATS guideline.1
In a previously published column, we have discussed the ATS’ recommended approaches for treating patients who are ready to stop smoking cigarettes. The reality is that many patients, if not most, are not ready to quit when we speak to them during any given office visit. The ATS guideline addresses this critical issue by recommending treatment with varenicline in patients who are not ready to stop smoking. It also states that this is a better strategy than waiting to start treatment until patients say they are ready for it.
This recommendation – to prescribe varenicline to smokers even when they are not ready to quit smoking – is based on solid clinical trial evidence. Research has shown that behavior change is dynamic and that the decision to stop smoking is not always a planned one.1 Patients often make quit attempts between office visits, and are often successful in those attempts. Because the decision to try to stop smoking is influenced by the satisfaction and physical addiction that comes from smoking, a medication such as varenicline that is a partial agonist/antagonist at the alpha4-beta2 nicotinic receptor might increase the likelihood that a patient would decide to try to stop smoking. This is because taking this type of a drug would lead the patient to no longer experience the reinforcing effects of nicotine.2 This hypothesis was examined in five randomized trials.1
In these studies, regular smokers who were not ready to make a quit attempt were randomized to varenicline versus placebo. Twice as many individuals who took varenicline stopped smoking 6 months after starting treatment.1
Suggested treatment
This patient should be offered varenicline. This individual meets the criteria for this treatment according to the ATS guideline in that the patient is a regular smoker who doesn’t think she is ready to stop smoking but understands she needs to stop and is open to taking medication to assist her with quitting.
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 (Pa.) Hospital–Jefferson Health. Dr. Sprogell is a third-year resident in the family medicine residency program at Abington Jefferson Health. They have no conflicts related to the content of this piece. For questions or comments, feel free to contact Dr. Skolnik on Twitter @NeilSkolnik.
References
1. Leone F T et al. Initiating pharmacologic treatment in tobacco-dependent adults: An official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Jul 15;202(2):e5–e31.
2. Ebbert JO et al. Varenicline for smoking cessation: Efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010;4:355-62.
CDC playbook prepares states for rollout of COVID-19 vaccine if one is approved
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.
Nationwide study questions routine long-term beta-blocker post MI
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
Current American and European guidelines recommending long-term beta-blocker therapy following an acute MI appear to be obsolete in the modern reperfusion era, suggests an analysis of Danish registry data.
Those guidelines are based on old randomized trials of beta-blocker therapy conducted prior to introduction of routine percutaneous coronary intervention and modern multidrug optimal medical therapy for acute MI. There have been no prospective controlled studies in the reperfusion era. And a new Danish national observational study strongly suggests it’s time to reexamine the beta-blocker recommendation, Anders Holt, MD, said at the virtual annual congress of the European Society of Cardiology.
“Stable, optimally treated MI patients do not seem to benefit from beta-blocker treatment exceeding 3 months post hospitalization – bearing in mind this doesn’t apply to patients with other indications for beta-blockers, like heart failure or atrial fibrillation,” said Dr. Holt of Copenhagen University Hospital.
His analysis of Danish national registry data on more than 30,000 patients hospitalized for acute MI during 2003-2018 earned him the annual ESC Young Investigator Award in Population Science.
“This was a crisp and clear presentation of a very creative use of observational epidemiology to try to understand the length of therapy that may or may not be appropriate,” commented award session cochair Paul M. Ridker, MD, director of the Center for Cardiovascular Disease Prevention at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, both in Boston.
Dr. Holt reported on 30,177 patients optimally treated for a first MI in Danish hospitals during 2003-2018, none of whom had a prior indication or contraindication for beta-blocker therapy. “Optimally treated” meant they underwent percutaneous coronary revascularization and were discharged on a statin and aspirin. As a study requirement, all had to be stable 90 days post hospitalization, at which point 24,770 of the patients were on long-term beta-blocker therapy, and 5,407 (18%) were not. The two groups were comparable in terms of age, sex, comorbidities, and baseline medications. All patients were followed through the registries for a maximum of 3 years, the duration of beta-blocker therapy post MI recommended in American Heart Association/American College of Cardiology guidelines. (The Danish Society of Cardiology recommends 2 years.)
At 3 years post MI, there was no between-group difference in a composite outcome comprising cardiovascular death, recurrent MI, heart failure, stroke, angina, or a cardiac procedure, with a rate of 22.9% in the beta-blocker group and 21.6% in patients not on long-term beta-blocker therapy. The rate of recurrent MI was identical at 6.7% in both groups. Cardiovascular death occurred during 3 years of follow-up in 1.4% of patients on beta-blocker therapy and 1.7% who weren’t, a nonsignificant difference.
“We saw no evidence of any cardioprotective effect, but no increased risk of adverse events resulting in hospitalization, either,” Dr. Holt observed. “I would like to acknowledge that no evidence of effect does not necessarily equal evidence of no effect, but even if there was an effect we can with fair certainty say that it’s probably quite minimal.”
He noted that the Danish registry data indicates that each year since 2012 has shown a growing trend for Danish patients to dispense with long-term beta-blocker therapy after an acute MI.
“This might indicate we are nudging toward a change in practice, where more physicians are thinking that long-term beta-blocker therapy might not be indicated for all MI patients in the reperfusion era,” according to Dr. Holt.
Asked by the four-judge award panel about the possibility of unmeasured confounding in this observational study, Dr Holt responded: “I would be very cautious about asking patients to stop beta-blocker therapy after 3 months just based on this observational data. We can’t speak to causality in an observational study.” But he added that “well-designed observational studies provide valuable data regarding this topic and should not be ignored. They should possibly influence the guidelines and the designs for upcoming randomized trials.”
He conducted several supplementary analyses designed to address the possibility of unevenly distributed unmeasured confounding in the registry study. These analyses proved reassuring. A positive exposure control analysis compared 3-year outcomes in patients who remained on long-term statin therapy and those who didn’t. As expected, outcomes were significantly better in those who did: a 3-year composite outcome rate of 22.1%, compared with 32.1% in patients not on a statin; a cardiovascular death rate of 1.3% with and 2.1% without statin therapy; a recurrent MI rate of 6.6%, compared with 10.1% without a statin; and a 2.8% all-cause mortality with and 5.4% without statin therapy.
In contrast, all-cause mortality was unaffected by whether or not patients were on long-term beta-blocker therapy. And in a negative exposure outcome analysis, no association was found between beta-blocker therapy and the risk of hospitalization for pneumonia, as to be expected if the beta-blocker and no-beta-blocker groups were comparable in key respects.
Dr. Holt reported having no financial conflicts regarding his study.
FROM ESC CONGRESS 2020
Three major COVID vaccine developers release detailed trial protocols
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.
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.
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.
Smart health devices – promises and pitfalls
What needs to be done before the data deluge hits the office
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.
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.
What needs to be done before the data deluge hits the office
What needs to be done before the data deluge hits the office
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.
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.
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.
Children’s share of COVID-19 burden continues to increase
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
Children continue to represent an increasing proportion of reported COVID-19 cases in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.
The previous week, children represented 10.0% of all cases, and that proportion has continued to rise throughout the pandemic, the AAP and CHA report shows.
Looking at just new cases for the latest week, the 38,000+ pediatric cases made up almost 17% of the 228,396 cases reported for all ages, compared with 16% and 15% the two previous weeks. For the weeks ending Aug. 13 and Aug. 6, the corresponding figures were 8% and 13%, based on the data in the AAP/CHA report, which cover 49 states (New York City but not New York state), the District of Columbia, Puerto Rico, and Guam.
The state with the highest proportion of child COVID-19 cases as of Sept. 17 was Wyoming, with 20.6%, followed by North Dakota at 18.3% and Tennessee at 17.9%. New York City has a cumulative rate of just 3.4%, but New Jersey is the state with the lowest rate at 3.6%. Florida comes in at 5.9% but is using an age range of 0-14 years for children, and Texas has a rate of 6.0% but has reported ages for only 8% of confirmed cases, the AAP and CHA noted.
Severe illness, however, continues to be rare in children. The overall hospitalization rate for children was down to 1.7% among the 26 jurisdictions providing ages as Sept. 17 – down from 1.8% the week before and 2.3% on Aug. 20. The death rate is just 0.02% among 43 jurisdictions, the report said.
More female specialists, but gender gap persists in pay, survey finds
More female physicians are becoming specialists, a Medscape survey finds, and five specialties have seen particularly large increases during the last 5 years.
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
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.
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
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.
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
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.
Signs of an ‘October vaccine surprise’ alarm career scientists
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.
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.
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.
Sotorasib is a ‘triumph of drug discovery’ in cancer
KRAS, one of the most frequently mutated oncogenes in human cancer, has long been thought to be “undruggable,” but early results from a clinical trial of the experimental KRAS inhibitor sotorasib (Amgen) suggest that at least one KRAS mutation common in non–small cell lung cancers (NSCLC) has a soft underbelly.
In the phase 1 CodeBreaK 100 trial, sotorasib, an investigational first-in-class inhibitor of the KRAS p.G12C mutation, showed encouraging activity against advanced NSCLC and other solid tumors.
Among patients with NSCLC, 19 (32.2%) of 59 had a confirmed objective response to sotorasib monotherapy, and 52 (88.1%) had disease control, reported David S. Hong, MD, from the University of Texas MD Anderson Cancer Center, Houston.
“Sotorasib also demonstrated durable disease control in heavily pretreated patients with non–small cell lung cancer,” said Dr. Hong.
He presented secondary efficacy endpoint results from the trial in an online presentation during the European Society of Medical Oncology Virtual Congress 2020. The study was also published simultaneously online in the New England Journal of Medicine.
The trial met its primary endpoint of safety of sotorasib, with no dose-limiting toxicities or treatment-related fatal adverse events, and treatment-emergent grade 3 or higher adverse events occurring in less than 20% of patients.
“The safety profile is more favorable than that of other targeted agents, and I think the reason why you have a quite safe compound here is that sotorasib is very specific in its binding to KRAS G12C, and KRAS G12C is only present in the tumor,” coinvestigator Marwan G. Fakih, MD, a medical oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview. Fakih was co–lead author of the report in the New England Journal of Medicine.
A real “triumph”
Sotorasib is “a triumph of drug discovery,” commented Colin Lindsay, MD, from the University of Manchester (England), the invited discussant.
“We know that KRAS, over many years, over 3 decades, has been very difficult to target,” he said.
“The early development of KRAS G12C–targeted agents is just the beginning, lending hope that the ability to target not only other KRAS mutations but also other targets previously thought to be undruggable may be within reach,” write Patricia M. LoRusso, DO, from the Yale Cancer Center in New Haven, Conn., and Judith S. Sebolt-Leopold, PhD, from the University of Michigan Rogel Cancer Center, Ann Arbor, in an accompanying editorial.
The KRAS, which stands for Kristen rat sarcoma viral oncogene homologue, p.G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form. The mutation has been identified in approximately 13% of NSCLC tumors, in 1% to 7% of colorectal cancers, and in other solid tumors.
But the mutation has been considered too difficult to target because of KRAS’ strong binding affinity for guanosine triphosphate (GTP), an essential building block of RNA synthesis, and by a lack of accessible drug binding sites.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form, Dr. Fakih explained.
Study details
The CodeBreaK 100 investigators enrolled patients with 13 different locally advanced or metastatic solid tumor types, all bearing the KRAS p.G12C mutation.
The trial began with a dose-escalation phase, with two to four patients per cohort assigned to receive daily oral sotorasib at doses of 180, 360, 720, or 960 mg. The 960 mg dose was selected for expansion cohorts and for planned phase 2 studies, based on the safety profile and the lack of dose-limiting toxicities.
Hong and colleagues reported results for 129 patients treated in the dose-escalation and expansion cohorts, including 59 with NSCLC, 42 with colorectal cancer and 28 with other tumor types, but focused primarily on patients with NSCLC.
After a median follow-up of 11.7 months, 59 patients with NSCLC had been treated, 3 at the 180 mg dose, 16 at 360 mg, 6 at 720 mg, and 34 at 960 mg. At the time of data cutoff in June of this year, 14 patients were still on treatment and 45 had discontinued, either from disease progression (35 patients), death (5), patient request (4) or adverse events (1).
As noted, there were no dose-limiting toxicities or treatment-related fatalities reported.
Grade 3-4 treatment-related adverse events were reported in 18.6% of patients. The only grade 4 treatment-related event was diarrhea, in one patient. Grade 3 events included elevated liver transaminases in nine patients, increased alkaline phosphatase in two, anemia in one, and increased gamma-glutamyl transferase levels, decreased lymphocyte count, hepatitis, and hyponatremia in one patient each.
Dr. Fakih said that, given sotorasib’s high degree of specificity, it’s unclear what might be causing the observed adverse events.
Responses at all dose levels
The confirmed partial response rate was 32.2% for patients with NSCLC treated at all dose levels, and 35.3% for patients who received the 960 mg dose.
Among all NSCLC patients, and all treated at the highest 960-mg dose level, the stable disease rates were 55.9%. The respective disease control rates were 88.1% and 91.2%.
Tumor reductions occurred across all dose levels in patients with NSCLC. The median progression-free survival was 6.3 months.
Hong reported results for one patient, a 59-year-old man with the mutation who had experienced disease progression on five prior therapies including targeted agents, chemotherapy, and a checkpoint inhibitor, and had gamma-knife surgery for brain lesions.
This patient had a complete response in target lesions and a partial response overall, which included shrinkage of central nervous system metastases. He recently had progression in non-target lesions, after 1.5 years in response, Dr. Hong said.
The median duration of response was 10.9 months for patients with partial responses and 4 months for patients with stable disease.
Hong noted that response to sotorasib was seen across a range of co-mutational profiles, including several patients with four mutations in addition to KRAS p.G12C.
Other tumors, possible combinations
Among 42 patients with colorectal cancers bearing the KRAS p.G12C mutation, 3 (7.1%) had a partial response. There were also partial responses seen in one patient each with melanoma and with appendiceal, endometrial, and pancreatic tumors.
“Overall, the results of this trial are very encouraging, showing the first step in ‘drugging the undruggable,’ ” Dr. LoRusso and Dr. Sebolt-Leopold wrote in their editorial.
They suggested that therapy with sotorasib may be improved by combining it with other agents that could target resistance to KRAS inhibition.
“A recent study showed that KRAS G12C colorectal cancer cells have higher basal epidermal growth factor receptor (EGFR) activity than NSCLC cells, leading to a rapid rebound in mitogen-activated protein (MAP) kinase signaling and resistance to KRAS G12C inhibition,” the editorialists wrote. “This observation is consistent with the weaker observed clinical activity of sotorasib in patients with colorectal cancer, a problem that may be addressed by combining it with an EGFR inhibitor [e.g., cetuximab], as seen preclinically.”
“I think this drug is being positioned not only in refractory disease, but we’re hoping to see it move upfront in non–small cell lung cancer, and we’re hoping to improve its efficacy in colorectal cancer,” Dr. Fakih said in an interview.
The study was sponsored by Amgen and by grants from the National Institutes of Health. Dr. Hong disclosed research/grant funding and an advisory/consulting role with Amgen and others. Dr. Fakih disclosed a speaking engagement for Amgen and consulting for and grant support from others. Dr. Lindsay disclosed consulting for Amgen and institutional research funding from the company and others. Dr. LoRusso disclosed fees from multiple companies, not including Amgen. Dr. Sebolt-Leopold disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
KRAS, one of the most frequently mutated oncogenes in human cancer, has long been thought to be “undruggable,” but early results from a clinical trial of the experimental KRAS inhibitor sotorasib (Amgen) suggest that at least one KRAS mutation common in non–small cell lung cancers (NSCLC) has a soft underbelly.
In the phase 1 CodeBreaK 100 trial, sotorasib, an investigational first-in-class inhibitor of the KRAS p.G12C mutation, showed encouraging activity against advanced NSCLC and other solid tumors.
Among patients with NSCLC, 19 (32.2%) of 59 had a confirmed objective response to sotorasib monotherapy, and 52 (88.1%) had disease control, reported David S. Hong, MD, from the University of Texas MD Anderson Cancer Center, Houston.
“Sotorasib also demonstrated durable disease control in heavily pretreated patients with non–small cell lung cancer,” said Dr. Hong.
He presented secondary efficacy endpoint results from the trial in an online presentation during the European Society of Medical Oncology Virtual Congress 2020. The study was also published simultaneously online in the New England Journal of Medicine.
The trial met its primary endpoint of safety of sotorasib, with no dose-limiting toxicities or treatment-related fatal adverse events, and treatment-emergent grade 3 or higher adverse events occurring in less than 20% of patients.
“The safety profile is more favorable than that of other targeted agents, and I think the reason why you have a quite safe compound here is that sotorasib is very specific in its binding to KRAS G12C, and KRAS G12C is only present in the tumor,” coinvestigator Marwan G. Fakih, MD, a medical oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview. Fakih was co–lead author of the report in the New England Journal of Medicine.
A real “triumph”
Sotorasib is “a triumph of drug discovery,” commented Colin Lindsay, MD, from the University of Manchester (England), the invited discussant.
“We know that KRAS, over many years, over 3 decades, has been very difficult to target,” he said.
“The early development of KRAS G12C–targeted agents is just the beginning, lending hope that the ability to target not only other KRAS mutations but also other targets previously thought to be undruggable may be within reach,” write Patricia M. LoRusso, DO, from the Yale Cancer Center in New Haven, Conn., and Judith S. Sebolt-Leopold, PhD, from the University of Michigan Rogel Cancer Center, Ann Arbor, in an accompanying editorial.
The KRAS, which stands for Kristen rat sarcoma viral oncogene homologue, p.G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form. The mutation has been identified in approximately 13% of NSCLC tumors, in 1% to 7% of colorectal cancers, and in other solid tumors.
But the mutation has been considered too difficult to target because of KRAS’ strong binding affinity for guanosine triphosphate (GTP), an essential building block of RNA synthesis, and by a lack of accessible drug binding sites.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form, Dr. Fakih explained.
Study details
The CodeBreaK 100 investigators enrolled patients with 13 different locally advanced or metastatic solid tumor types, all bearing the KRAS p.G12C mutation.
The trial began with a dose-escalation phase, with two to four patients per cohort assigned to receive daily oral sotorasib at doses of 180, 360, 720, or 960 mg. The 960 mg dose was selected for expansion cohorts and for planned phase 2 studies, based on the safety profile and the lack of dose-limiting toxicities.
Hong and colleagues reported results for 129 patients treated in the dose-escalation and expansion cohorts, including 59 with NSCLC, 42 with colorectal cancer and 28 with other tumor types, but focused primarily on patients with NSCLC.
After a median follow-up of 11.7 months, 59 patients with NSCLC had been treated, 3 at the 180 mg dose, 16 at 360 mg, 6 at 720 mg, and 34 at 960 mg. At the time of data cutoff in June of this year, 14 patients were still on treatment and 45 had discontinued, either from disease progression (35 patients), death (5), patient request (4) or adverse events (1).
As noted, there were no dose-limiting toxicities or treatment-related fatalities reported.
Grade 3-4 treatment-related adverse events were reported in 18.6% of patients. The only grade 4 treatment-related event was diarrhea, in one patient. Grade 3 events included elevated liver transaminases in nine patients, increased alkaline phosphatase in two, anemia in one, and increased gamma-glutamyl transferase levels, decreased lymphocyte count, hepatitis, and hyponatremia in one patient each.
Dr. Fakih said that, given sotorasib’s high degree of specificity, it’s unclear what might be causing the observed adverse events.
Responses at all dose levels
The confirmed partial response rate was 32.2% for patients with NSCLC treated at all dose levels, and 35.3% for patients who received the 960 mg dose.
Among all NSCLC patients, and all treated at the highest 960-mg dose level, the stable disease rates were 55.9%. The respective disease control rates were 88.1% and 91.2%.
Tumor reductions occurred across all dose levels in patients with NSCLC. The median progression-free survival was 6.3 months.
Hong reported results for one patient, a 59-year-old man with the mutation who had experienced disease progression on five prior therapies including targeted agents, chemotherapy, and a checkpoint inhibitor, and had gamma-knife surgery for brain lesions.
This patient had a complete response in target lesions and a partial response overall, which included shrinkage of central nervous system metastases. He recently had progression in non-target lesions, after 1.5 years in response, Dr. Hong said.
The median duration of response was 10.9 months for patients with partial responses and 4 months for patients with stable disease.
Hong noted that response to sotorasib was seen across a range of co-mutational profiles, including several patients with four mutations in addition to KRAS p.G12C.
Other tumors, possible combinations
Among 42 patients with colorectal cancers bearing the KRAS p.G12C mutation, 3 (7.1%) had a partial response. There were also partial responses seen in one patient each with melanoma and with appendiceal, endometrial, and pancreatic tumors.
“Overall, the results of this trial are very encouraging, showing the first step in ‘drugging the undruggable,’ ” Dr. LoRusso and Dr. Sebolt-Leopold wrote in their editorial.
They suggested that therapy with sotorasib may be improved by combining it with other agents that could target resistance to KRAS inhibition.
“A recent study showed that KRAS G12C colorectal cancer cells have higher basal epidermal growth factor receptor (EGFR) activity than NSCLC cells, leading to a rapid rebound in mitogen-activated protein (MAP) kinase signaling and resistance to KRAS G12C inhibition,” the editorialists wrote. “This observation is consistent with the weaker observed clinical activity of sotorasib in patients with colorectal cancer, a problem that may be addressed by combining it with an EGFR inhibitor [e.g., cetuximab], as seen preclinically.”
“I think this drug is being positioned not only in refractory disease, but we’re hoping to see it move upfront in non–small cell lung cancer, and we’re hoping to improve its efficacy in colorectal cancer,” Dr. Fakih said in an interview.
The study was sponsored by Amgen and by grants from the National Institutes of Health. Dr. Hong disclosed research/grant funding and an advisory/consulting role with Amgen and others. Dr. Fakih disclosed a speaking engagement for Amgen and consulting for and grant support from others. Dr. Lindsay disclosed consulting for Amgen and institutional research funding from the company and others. Dr. LoRusso disclosed fees from multiple companies, not including Amgen. Dr. Sebolt-Leopold disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
KRAS, one of the most frequently mutated oncogenes in human cancer, has long been thought to be “undruggable,” but early results from a clinical trial of the experimental KRAS inhibitor sotorasib (Amgen) suggest that at least one KRAS mutation common in non–small cell lung cancers (NSCLC) has a soft underbelly.
In the phase 1 CodeBreaK 100 trial, sotorasib, an investigational first-in-class inhibitor of the KRAS p.G12C mutation, showed encouraging activity against advanced NSCLC and other solid tumors.
Among patients with NSCLC, 19 (32.2%) of 59 had a confirmed objective response to sotorasib monotherapy, and 52 (88.1%) had disease control, reported David S. Hong, MD, from the University of Texas MD Anderson Cancer Center, Houston.
“Sotorasib also demonstrated durable disease control in heavily pretreated patients with non–small cell lung cancer,” said Dr. Hong.
He presented secondary efficacy endpoint results from the trial in an online presentation during the European Society of Medical Oncology Virtual Congress 2020. The study was also published simultaneously online in the New England Journal of Medicine.
The trial met its primary endpoint of safety of sotorasib, with no dose-limiting toxicities or treatment-related fatal adverse events, and treatment-emergent grade 3 or higher adverse events occurring in less than 20% of patients.
“The safety profile is more favorable than that of other targeted agents, and I think the reason why you have a quite safe compound here is that sotorasib is very specific in its binding to KRAS G12C, and KRAS G12C is only present in the tumor,” coinvestigator Marwan G. Fakih, MD, a medical oncologist at City of Hope Comprehensive Cancer Center in Duarte, Calif., said in an interview. Fakih was co–lead author of the report in the New England Journal of Medicine.
A real “triumph”
Sotorasib is “a triumph of drug discovery,” commented Colin Lindsay, MD, from the University of Manchester (England), the invited discussant.
“We know that KRAS, over many years, over 3 decades, has been very difficult to target,” he said.
“The early development of KRAS G12C–targeted agents is just the beginning, lending hope that the ability to target not only other KRAS mutations but also other targets previously thought to be undruggable may be within reach,” write Patricia M. LoRusso, DO, from the Yale Cancer Center in New Haven, Conn., and Judith S. Sebolt-Leopold, PhD, from the University of Michigan Rogel Cancer Center, Ann Arbor, in an accompanying editorial.
The KRAS, which stands for Kristen rat sarcoma viral oncogene homologue, p.G12C mutation is a glycine-to-cysteine substitution that results in the oncogene being switched on in its active form. The mutation has been identified in approximately 13% of NSCLC tumors, in 1% to 7% of colorectal cancers, and in other solid tumors.
But the mutation has been considered too difficult to target because of KRAS’ strong binding affinity for guanosine triphosphate (GTP), an essential building block of RNA synthesis, and by a lack of accessible drug binding sites.
Sotorasib is a small-molecule, specific, and irreversible inhibitor of KRAS that interacts with a “pocket” on the gene’s surface that is present only in an inactive conformation of KRAS. The drug inhibits oncogenic signaling and tumorigenesis by preventing cycling of the oncogene into its active form, Dr. Fakih explained.
Study details
The CodeBreaK 100 investigators enrolled patients with 13 different locally advanced or metastatic solid tumor types, all bearing the KRAS p.G12C mutation.
The trial began with a dose-escalation phase, with two to four patients per cohort assigned to receive daily oral sotorasib at doses of 180, 360, 720, or 960 mg. The 960 mg dose was selected for expansion cohorts and for planned phase 2 studies, based on the safety profile and the lack of dose-limiting toxicities.
Hong and colleagues reported results for 129 patients treated in the dose-escalation and expansion cohorts, including 59 with NSCLC, 42 with colorectal cancer and 28 with other tumor types, but focused primarily on patients with NSCLC.
After a median follow-up of 11.7 months, 59 patients with NSCLC had been treated, 3 at the 180 mg dose, 16 at 360 mg, 6 at 720 mg, and 34 at 960 mg. At the time of data cutoff in June of this year, 14 patients were still on treatment and 45 had discontinued, either from disease progression (35 patients), death (5), patient request (4) or adverse events (1).
As noted, there were no dose-limiting toxicities or treatment-related fatalities reported.
Grade 3-4 treatment-related adverse events were reported in 18.6% of patients. The only grade 4 treatment-related event was diarrhea, in one patient. Grade 3 events included elevated liver transaminases in nine patients, increased alkaline phosphatase in two, anemia in one, and increased gamma-glutamyl transferase levels, decreased lymphocyte count, hepatitis, and hyponatremia in one patient each.
Dr. Fakih said that, given sotorasib’s high degree of specificity, it’s unclear what might be causing the observed adverse events.
Responses at all dose levels
The confirmed partial response rate was 32.2% for patients with NSCLC treated at all dose levels, and 35.3% for patients who received the 960 mg dose.
Among all NSCLC patients, and all treated at the highest 960-mg dose level, the stable disease rates were 55.9%. The respective disease control rates were 88.1% and 91.2%.
Tumor reductions occurred across all dose levels in patients with NSCLC. The median progression-free survival was 6.3 months.
Hong reported results for one patient, a 59-year-old man with the mutation who had experienced disease progression on five prior therapies including targeted agents, chemotherapy, and a checkpoint inhibitor, and had gamma-knife surgery for brain lesions.
This patient had a complete response in target lesions and a partial response overall, which included shrinkage of central nervous system metastases. He recently had progression in non-target lesions, after 1.5 years in response, Dr. Hong said.
The median duration of response was 10.9 months for patients with partial responses and 4 months for patients with stable disease.
Hong noted that response to sotorasib was seen across a range of co-mutational profiles, including several patients with four mutations in addition to KRAS p.G12C.
Other tumors, possible combinations
Among 42 patients with colorectal cancers bearing the KRAS p.G12C mutation, 3 (7.1%) had a partial response. There were also partial responses seen in one patient each with melanoma and with appendiceal, endometrial, and pancreatic tumors.
“Overall, the results of this trial are very encouraging, showing the first step in ‘drugging the undruggable,’ ” Dr. LoRusso and Dr. Sebolt-Leopold wrote in their editorial.
They suggested that therapy with sotorasib may be improved by combining it with other agents that could target resistance to KRAS inhibition.
“A recent study showed that KRAS G12C colorectal cancer cells have higher basal epidermal growth factor receptor (EGFR) activity than NSCLC cells, leading to a rapid rebound in mitogen-activated protein (MAP) kinase signaling and resistance to KRAS G12C inhibition,” the editorialists wrote. “This observation is consistent with the weaker observed clinical activity of sotorasib in patients with colorectal cancer, a problem that may be addressed by combining it with an EGFR inhibitor [e.g., cetuximab], as seen preclinically.”
“I think this drug is being positioned not only in refractory disease, but we’re hoping to see it move upfront in non–small cell lung cancer, and we’re hoping to improve its efficacy in colorectal cancer,” Dr. Fakih said in an interview.
The study was sponsored by Amgen and by grants from the National Institutes of Health. Dr. Hong disclosed research/grant funding and an advisory/consulting role with Amgen and others. Dr. Fakih disclosed a speaking engagement for Amgen and consulting for and grant support from others. Dr. Lindsay disclosed consulting for Amgen and institutional research funding from the company and others. Dr. LoRusso disclosed fees from multiple companies, not including Amgen. Dr. Sebolt-Leopold disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
FROM ESMO 2020