Caleb Rans, PharmD

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.

Work load, not personal vulnerability, may be at the root of the current physician burnout crisis, a recent study has concluded.

The cutting-edge research utilized cognitive theory and work load analysis to get at the source of burnout among practitioners. The findings indicate that, although some institutions continue to emphasize personal responsibility of physicians to address the issue, it may be the amount and structure of the work itself that triggers burnout in doctors.

“We evaluated the cognitive load of a clinical workday in a national sample of U.S. physicians and its relationship with burnout and professional satisfaction,” wrote Elizabeth Harry, MD, SFHM, a hospitalist at the University of Colorado at Denver, Aurora and coauthors. The results were reported in the Joint Commission Journal on Quality and Patient Safety.

The researchers investigated whether task load correlated with burnout scores in a large national study of U.S. physicians from October 2017 to March 2018.

As the delivery of health care becomes more complex, physicians are charged with ever-increasing amount of administrative and cognitive tasks. Recent evidence indicates that this growing complexity of work is tied to a greater risk of burnout in physicians, compared with workers in other fields. Cognitive load theory, pioneered by psychologist Jonathan Sweller, identified limitations in working memory that humans depend on to carry out cognitive tasks. Cognitive load refers to the amount of working memory used, which can be reduced in the presence of external emotional or physiological stressors. While a potential link between cognitive load and burnout may seem self-evident, the correlation between the cognitive load of physicians and burnout has not been evaluated in a large-scale study until recently.

wutwhanfoto/Getty Images

Physician task load (PTL) was measured using the National Aeronautics and Space Administration Task Load Index (NASA-TLX), a validated questionnaire frequently used to evaluate the cognitive load of work environments, including health care environments. Four domains (perception of effort and mental, physical, and temporal demands) were used to calculate the total PTL score.

Burnout was evaluated using the Emotional Exhaustion and Depersonalization scales of the Maslach Burnout Inventory, a validated tool considered the gold standard for measurement.

The survey sample consisted of physicians of all specialties and was assembled using the American Medical Association Physician Masterfile, an almost complete record of all U.S. physicians independent of AMA membership. All responses were anonymous and participation was voluntary.
 

Results

Among 30,456 physicians who received the survey, 5,197 (17.1%) responded. In total, 5,276 physicians were included in the analysis.

The median age of respondents was 53 years, and 61.8% self-identified as male. Twenty-four specialties were identified: 23.8% were from a primary care discipline and internal medicine represented the largest respondent group (12.1%).

Almost half of respondents (49.7%) worked in private practice, and 44.8% had been in practice for 21 years or longer.

Overall, 44.0% had at least one symptom of burnout, 38.8% of participants scored in the high range for emotional exhaustion, and 27.4% scored in the high range for depersonalization. The mean score in task load dimension varied by specialty.

The mean PTL score was 260.9 (standard deviation, 71.4). The specialties with the highest PTL score were emergency medicine (369.8), urology (353.7), general surgery subspecialties (343.9), internal medicine subspecialties (342.2), and radiology (341.6).

Aside from specialty, PTL scores also varied by practice setting, gender, age, number of hours worked per week, number of nights on call per week, and years in practice.

The researchers observed a dose response relationship between PTL and risk of burnout. For every 40-point (10%) reduction in PTL, there was 33% lower odds of experiencing burnout (odds ratio, 0.67; 95% confidence interval, 0.65-0.70; P < .0001). Multivariable analyses also indicated that PTL was a significant predictor of burnout, independent of practice setting, specialty, age, gender, and hours worked.
 

Organizational strategies to reduce physician burnout

Coauthors of the study, Tait D. Shanafelt, MD, professor of medicine at Stanford (Calif.) University and Colin P. West, MD, PhD, of the Mayo Clinic in Rochester, Minn., are both experts on physician well-being and are passionate about finding new ways to reduce physician distress and improving health care delivery.

“Authentic efforts to address this problem must move beyond personal resilience,” Dr. Shanafelt said in an interview. “Organizations that fail to get serious about this issue are going to be left behind and struggle in the war for talent.

“Much like our efforts to improve quality, advancing clinician well-being requires organizations to make it a priority and establish the structure, process, and leadership to promote the desired outcomes,” said Dr. Shanafelt.

One potential strategy for improvement is appointing a chief wellness officer, a dedicated individual within the health care system that leads the organizational effort, explained Dr. Shanafelt. “Over 30 vanguard institutions across the United States have already taken this step.”

Dr. West, a coauthor of the study, explained that conducting an analysis of PTL is fairly straightforward for hospitals and individual institutions. “The NASA-TLX tool is widely available, free to use, and not overly complex, and it could be used to provide insight into physician effort and mental, physical, and temporal demand levels,” he said in an interview.

“Deeper evaluations could follow to identify specific potential solutions, particularly system-level approaches to alleviate PTL,” Dr. West explained. “In the short term, such analyses and solutions would have costs, but helping physicians work more optimally and with less chronic strain from excessive task load would save far more than these costs overall.”

Dr. West also noted that physician burnout is very expensive to a health care system, and strategies to promote physician well-being would be a prudent financial decision long term for health care organizations.

Dr. Harry, lead author of the study, agreed with Dr. West, noting that “quality improvement literature has demonstrated that improvements in inefficiencies that lead to increased demand in the workplace often has the benefit of reduced cost.

“Many studies have demonstrated the risk of turnover due to burnout and the significant cost of physician turn over,” she said in an interview. “This cost avoidance is well worth the investment in improved operations to minimize unnecessary task load.”

Dr. Harry also recommended the NASA-TLX tool as a free resource for health systems and organizations. She noted that future studies will further validate the reliability of the tool.

“At the core, we need to focus on system redesign at both the micro and the macro level,” Dr. Harry said. “Each health system will need to assess inefficiencies in their work flow, while regulatory bodies need to consider the downstream task load of mandates and reporting requirements, all of which contribute to more cognitive load.”

The study was supported by funding from the Stanford Medicine WellMD Center, the American Medical Association, and the Mayo Clinic department of medicine program on physician well-being. Coauthors Lotte N. Dyrbye, MD, and Dr. Shanafelt are coinventors of the Physician Well-being Index, Medical Student Well-Being Index, Nurse Well-Being, and Well-Being Index. Mayo Clinic holds the copyright to these instruments and has licensed them for external use. Dr. Dyrbye and Dr. Shanafelt receive a portion of any royalties paid to Mayo Clinic. All other authors reported no conflicts of interest.

An artificial intelligence (AI) diagnostic system based on neural networks may assist in the diagnosis of COVID-19, according to a pilot study.

The system, called CXR-Net, was trained to differentiate SARS-CoV-2 chest x-rays (CXRs) from CXRs that are either normal or non–COVID-19 lung pathologies, explained Abdulah Haikal, an MD candidate at Wayne State University, Detroit.

Mr. Haikal described CXR-Net at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S11-04).

CXR-Net is a two-module pipeline, Mr. Haikal explained. Module I is based on Res-CR-Net, a type of neural network originally designed for the semantic segmentation of microscopy images, with the ability to retain the original resolution of the input images in the feature maps of all layers and in the final output.

Module II is a hybrid convolutional neural network in which the first convolutional layer with learned coefficients is replaced by a layer with fixed coefficients provided by the Wavelet Scattering Transform. Module II inputs patients’ CXRs and corresponding lung masks quantified by Module I, and generates as outputs a class assignment (COVID-19 or non–COVID-19) and high-resolution heat maps that detect the severe acute respiratory syndrome–-associated lung regions.

“The system is trained to differentiate COVID and non-COVID pathologies and produces a highly discriminative heat map to point to lung regions where COVID is suspected,” Mr. Haikal said. “The Wavelet Scattering Transform allows for fast determination of COVID versus non-COVID CXRs.”
 

Preliminary results and implications

CXR-Net was piloted on a small dataset of CXRs from non–COVID-19 and polymerase chain reaction–confirmed COVID-19 patients acquired at a single center in Detroit.

Upon fivefold cross validation of the training set with 2,265 images, 90% accuracy was observed when the training set was tested against the validation set. However, once 1,532 new images were introduced, a 76% accuracy rate was observed.

The F1 scores were 0.81 and 0.70 for the training and test sets, respectively.

“I’m really excited about this new approach, and I think AI will allow us to do more with less, which is exciting,” said Ross L. Levine, MD, of Memorial Sloan Kettering Cancer Center in New York, who led a discussion session with Mr. Haikal about CXR-Net.

One question raised during the discussion was whether the technology will help health care providers be more thoughtful about when and how they image COVID-19 patients.

“The more data you feed into the system, the stronger and more accurate it becomes,” Mr. Haikal said. “However, until we have data sharing from multiple centers, we won’t see improved accuracy results.”

Another question was whether this technology could be integrated with more clinical parameters.

“Some individuals are afraid that AI will replace the job of a professional, but it will only make it better for us,” Mr. Haikal said. “We don’t rely on current imaging techniques to make a definitive diagnosis, but rather have a specificity and sensitivity to establish a diagnosis, and AI can be used in the same way as a diagnostic tool.”

Mr. Haikal and Dr. Levine disclosed no conflicts of interest. No funding sources were reported in the presentation.

An artificial intelligence (AI) diagnostic system based on neural networks may assist in the diagnosis of COVID-19, according to a pilot study.

The system, called CXR-Net, was trained to differentiate SARS-CoV-2 chest x-rays (CXRs) from CXRs that are either normal or non–COVID-19 lung pathologies, explained Abdulah Haikal, an MD candidate at Wayne State University, Detroit.

Mr. Haikal described CXR-Net at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S11-04).

CXR-Net is a two-module pipeline, Mr. Haikal explained. Module I is based on Res-CR-Net, a type of neural network originally designed for the semantic segmentation of microscopy images, with the ability to retain the original resolution of the input images in the feature maps of all layers and in the final output.

Module II is a hybrid convolutional neural network in which the first convolutional layer with learned coefficients is replaced by a layer with fixed coefficients provided by the Wavelet Scattering Transform. Module II inputs patients’ CXRs and corresponding lung masks quantified by Module I, and generates as outputs a class assignment (COVID-19 or non–COVID-19) and high-resolution heat maps that detect the severe acute respiratory syndrome–-associated lung regions.

“The system is trained to differentiate COVID and non-COVID pathologies and produces a highly discriminative heat map to point to lung regions where COVID is suspected,” Mr. Haikal said. “The Wavelet Scattering Transform allows for fast determination of COVID versus non-COVID CXRs.”
 

Preliminary results and implications

CXR-Net was piloted on a small dataset of CXRs from non–COVID-19 and polymerase chain reaction–confirmed COVID-19 patients acquired at a single center in Detroit.

Upon fivefold cross validation of the training set with 2,265 images, 90% accuracy was observed when the training set was tested against the validation set. However, once 1,532 new images were introduced, a 76% accuracy rate was observed.

The F1 scores were 0.81 and 0.70 for the training and test sets, respectively.

“I’m really excited about this new approach, and I think AI will allow us to do more with less, which is exciting,” said Ross L. Levine, MD, of Memorial Sloan Kettering Cancer Center in New York, who led a discussion session with Mr. Haikal about CXR-Net.

One question raised during the discussion was whether the technology will help health care providers be more thoughtful about when and how they image COVID-19 patients.

“The more data you feed into the system, the stronger and more accurate it becomes,” Mr. Haikal said. “However, until we have data sharing from multiple centers, we won’t see improved accuracy results.”

Another question was whether this technology could be integrated with more clinical parameters.

“Some individuals are afraid that AI will replace the job of a professional, but it will only make it better for us,” Mr. Haikal said. “We don’t rely on current imaging techniques to make a definitive diagnosis, but rather have a specificity and sensitivity to establish a diagnosis, and AI can be used in the same way as a diagnostic tool.”

Mr. Haikal and Dr. Levine disclosed no conflicts of interest. No funding sources were reported in the presentation.

An artificial intelligence (AI) diagnostic system based on neural networks may assist in the diagnosis of COVID-19, according to a pilot study.

The system, called CXR-Net, was trained to differentiate SARS-CoV-2 chest x-rays (CXRs) from CXRs that are either normal or non–COVID-19 lung pathologies, explained Abdulah Haikal, an MD candidate at Wayne State University, Detroit.

Mr. Haikal described CXR-Net at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S11-04).

CXR-Net is a two-module pipeline, Mr. Haikal explained. Module I is based on Res-CR-Net, a type of neural network originally designed for the semantic segmentation of microscopy images, with the ability to retain the original resolution of the input images in the feature maps of all layers and in the final output.

Module II is a hybrid convolutional neural network in which the first convolutional layer with learned coefficients is replaced by a layer with fixed coefficients provided by the Wavelet Scattering Transform. Module II inputs patients’ CXRs and corresponding lung masks quantified by Module I, and generates as outputs a class assignment (COVID-19 or non–COVID-19) and high-resolution heat maps that detect the severe acute respiratory syndrome–-associated lung regions.

“The system is trained to differentiate COVID and non-COVID pathologies and produces a highly discriminative heat map to point to lung regions where COVID is suspected,” Mr. Haikal said. “The Wavelet Scattering Transform allows for fast determination of COVID versus non-COVID CXRs.”
 

Preliminary results and implications

CXR-Net was piloted on a small dataset of CXRs from non–COVID-19 and polymerase chain reaction–confirmed COVID-19 patients acquired at a single center in Detroit.

Upon fivefold cross validation of the training set with 2,265 images, 90% accuracy was observed when the training set was tested against the validation set. However, once 1,532 new images were introduced, a 76% accuracy rate was observed.

The F1 scores were 0.81 and 0.70 for the training and test sets, respectively.

“I’m really excited about this new approach, and I think AI will allow us to do more with less, which is exciting,” said Ross L. Levine, MD, of Memorial Sloan Kettering Cancer Center in New York, who led a discussion session with Mr. Haikal about CXR-Net.

One question raised during the discussion was whether the technology will help health care providers be more thoughtful about when and how they image COVID-19 patients.

“The more data you feed into the system, the stronger and more accurate it becomes,” Mr. Haikal said. “However, until we have data sharing from multiple centers, we won’t see improved accuracy results.”

Another question was whether this technology could be integrated with more clinical parameters.

“Some individuals are afraid that AI will replace the job of a professional, but it will only make it better for us,” Mr. Haikal said. “We don’t rely on current imaging techniques to make a definitive diagnosis, but rather have a specificity and sensitivity to establish a diagnosis, and AI can be used in the same way as a diagnostic tool.”

Mr. Haikal and Dr. Levine disclosed no conflicts of interest. No funding sources were reported in the presentation.

Asymptomatic screening of cancer patients receiving anticancer therapy detected a very low rate of COVID-19 in a retrospective study.

Of more than 2,000 patients, less than 1% were found to be COVID-19 positive on asymptomatic screening, an investigator reported at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S09-04).

While several models have been proposed to screen for COVID-19 among cancer patients, the optimal strategy remains unknown, said investigator Justin A. Shaya, MD, of the University of California, San Diego.

The most commonly used approach is symptom/exposure-based screening and testing. However, other models have combined this method with polymerase chain reaction (PCR) testing for asymptomatic high-risk patients (such as those undergoing bone marrow transplant, receiving chemotherapy, or with hematologic malignancies) or with PCR testing for all asymptomatic cancer patients.

Dr. Shaya’s institution implemented a novel COVID-19 screening protocol for cancer patients receiving infusional anticancer therapy in May 2020.

The protocol required SARS-CoV-2 PCR testing for asymptomatic patients 24-96 hours prior to infusion. However, testing was only required before the administration of anticancer therapy. Infusion visits for supportive care interventions did not require previsit testing.

The researchers retrospectively analyzed data from patients with active cancer receiving infusional anticancer therapy who had at least one asymptomatic SARS-CoV-2 PCR test between June 1 and Dec. 1, 2020. The primary outcome was the rate of COVID-19 positivity among asymptomatic patients.

Results

Among 2,202 patients identified, 21 (0.95%) were found to be COVID-19 positive on asymptomatic screening. Most of these patients (90.5%) had solid tumors, but two (9.5%) had hematologic malignancies.

With respect to treatment, 16 patients (76.2%) received cytotoxic chemotherapy, 2 (9.5%) received targeted therapy, 1 (4.7%) received immunotherapy, and 2 (9.5%) were on a clinical trial.

At a median follow-up of 174 days from a positive PCR test (range, 55-223 days), only two patients (9.5%) developed COVID-related symptoms. Both patients had acute leukemia, and one required hospitalization for COVID-related complications.

In the COVID-19–positive cohort, 20 (95.2%) patients had their anticancer therapy delayed or deferred, with a median delay of 21 days (range, 7-77 days).

In the overall cohort, an additional 26 patients (1.2%) developed symptomatic COVID-19 during the study period.

“These results are particularly interesting because they come from a high-quality center that sees a large number of patients,” said Solange Peters, MD, PhD, of the University of Lausanne (Switzerland), who was not involved in this study.

“As they suggest, it is still a debate on how efficient routine screening is, asking the question whether we’re really detecting COVID-19 infection in our patients. Of course, it depends on the time and environment,” Dr. Peters added.

Dr. Shaya acknowledged that the small sample size was a key limitation of the study. Thus, the results may not be generalizable to other regions.

“One of the most striking things is that asymptomatic patients suffer very few consequences of COVID-19 infection, except for patients with hematologic malignancies,” Dr. Shaya said during a live discussion. “The majority of our patients had solid tumors and failed to develop any signs/symptoms of COVID infection.

“Routine screening provides a lot of security, and our institution is big enough to allow for it, and it seems our teams enjoy the fact of knowing the COVID status for each patient,” he continued.

Dr. Shaya and Dr. Peters disclosed no conflicts of interest. No funding sources were reported in the presentation.

Asymptomatic screening of cancer patients receiving anticancer therapy detected a very low rate of COVID-19 in a retrospective study.

Of more than 2,000 patients, less than 1% were found to be COVID-19 positive on asymptomatic screening, an investigator reported at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S09-04).

While several models have been proposed to screen for COVID-19 among cancer patients, the optimal strategy remains unknown, said investigator Justin A. Shaya, MD, of the University of California, San Diego.

The most commonly used approach is symptom/exposure-based screening and testing. However, other models have combined this method with polymerase chain reaction (PCR) testing for asymptomatic high-risk patients (such as those undergoing bone marrow transplant, receiving chemotherapy, or with hematologic malignancies) or with PCR testing for all asymptomatic cancer patients.

Dr. Shaya’s institution implemented a novel COVID-19 screening protocol for cancer patients receiving infusional anticancer therapy in May 2020.

The protocol required SARS-CoV-2 PCR testing for asymptomatic patients 24-96 hours prior to infusion. However, testing was only required before the administration of anticancer therapy. Infusion visits for supportive care interventions did not require previsit testing.

The researchers retrospectively analyzed data from patients with active cancer receiving infusional anticancer therapy who had at least one asymptomatic SARS-CoV-2 PCR test between June 1 and Dec. 1, 2020. The primary outcome was the rate of COVID-19 positivity among asymptomatic patients.

Results

Among 2,202 patients identified, 21 (0.95%) were found to be COVID-19 positive on asymptomatic screening. Most of these patients (90.5%) had solid tumors, but two (9.5%) had hematologic malignancies.

With respect to treatment, 16 patients (76.2%) received cytotoxic chemotherapy, 2 (9.5%) received targeted therapy, 1 (4.7%) received immunotherapy, and 2 (9.5%) were on a clinical trial.

At a median follow-up of 174 days from a positive PCR test (range, 55-223 days), only two patients (9.5%) developed COVID-related symptoms. Both patients had acute leukemia, and one required hospitalization for COVID-related complications.

In the COVID-19–positive cohort, 20 (95.2%) patients had their anticancer therapy delayed or deferred, with a median delay of 21 days (range, 7-77 days).

In the overall cohort, an additional 26 patients (1.2%) developed symptomatic COVID-19 during the study period.

“These results are particularly interesting because they come from a high-quality center that sees a large number of patients,” said Solange Peters, MD, PhD, of the University of Lausanne (Switzerland), who was not involved in this study.

“As they suggest, it is still a debate on how efficient routine screening is, asking the question whether we’re really detecting COVID-19 infection in our patients. Of course, it depends on the time and environment,” Dr. Peters added.

Dr. Shaya acknowledged that the small sample size was a key limitation of the study. Thus, the results may not be generalizable to other regions.

“One of the most striking things is that asymptomatic patients suffer very few consequences of COVID-19 infection, except for patients with hematologic malignancies,” Dr. Shaya said during a live discussion. “The majority of our patients had solid tumors and failed to develop any signs/symptoms of COVID infection.

“Routine screening provides a lot of security, and our institution is big enough to allow for it, and it seems our teams enjoy the fact of knowing the COVID status for each patient,” he continued.

Dr. Shaya and Dr. Peters disclosed no conflicts of interest. No funding sources were reported in the presentation.

Asymptomatic screening of cancer patients receiving anticancer therapy detected a very low rate of COVID-19 in a retrospective study.

Of more than 2,000 patients, less than 1% were found to be COVID-19 positive on asymptomatic screening, an investigator reported at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S09-04).

While several models have been proposed to screen for COVID-19 among cancer patients, the optimal strategy remains unknown, said investigator Justin A. Shaya, MD, of the University of California, San Diego.

The most commonly used approach is symptom/exposure-based screening and testing. However, other models have combined this method with polymerase chain reaction (PCR) testing for asymptomatic high-risk patients (such as those undergoing bone marrow transplant, receiving chemotherapy, or with hematologic malignancies) or with PCR testing for all asymptomatic cancer patients.

Dr. Shaya’s institution implemented a novel COVID-19 screening protocol for cancer patients receiving infusional anticancer therapy in May 2020.

The protocol required SARS-CoV-2 PCR testing for asymptomatic patients 24-96 hours prior to infusion. However, testing was only required before the administration of anticancer therapy. Infusion visits for supportive care interventions did not require previsit testing.

The researchers retrospectively analyzed data from patients with active cancer receiving infusional anticancer therapy who had at least one asymptomatic SARS-CoV-2 PCR test between June 1 and Dec. 1, 2020. The primary outcome was the rate of COVID-19 positivity among asymptomatic patients.

Results

Among 2,202 patients identified, 21 (0.95%) were found to be COVID-19 positive on asymptomatic screening. Most of these patients (90.5%) had solid tumors, but two (9.5%) had hematologic malignancies.

With respect to treatment, 16 patients (76.2%) received cytotoxic chemotherapy, 2 (9.5%) received targeted therapy, 1 (4.7%) received immunotherapy, and 2 (9.5%) were on a clinical trial.

At a median follow-up of 174 days from a positive PCR test (range, 55-223 days), only two patients (9.5%) developed COVID-related symptoms. Both patients had acute leukemia, and one required hospitalization for COVID-related complications.

In the COVID-19–positive cohort, 20 (95.2%) patients had their anticancer therapy delayed or deferred, with a median delay of 21 days (range, 7-77 days).

In the overall cohort, an additional 26 patients (1.2%) developed symptomatic COVID-19 during the study period.

“These results are particularly interesting because they come from a high-quality center that sees a large number of patients,” said Solange Peters, MD, PhD, of the University of Lausanne (Switzerland), who was not involved in this study.

“As they suggest, it is still a debate on how efficient routine screening is, asking the question whether we’re really detecting COVID-19 infection in our patients. Of course, it depends on the time and environment,” Dr. Peters added.

Dr. Shaya acknowledged that the small sample size was a key limitation of the study. Thus, the results may not be generalizable to other regions.

“One of the most striking things is that asymptomatic patients suffer very few consequences of COVID-19 infection, except for patients with hematologic malignancies,” Dr. Shaya said during a live discussion. “The majority of our patients had solid tumors and failed to develop any signs/symptoms of COVID infection.

“Routine screening provides a lot of security, and our institution is big enough to allow for it, and it seems our teams enjoy the fact of knowing the COVID status for each patient,” he continued.

Dr. Shaya and Dr. Peters disclosed no conflicts of interest. No funding sources were reported in the presentation.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

Best practices for managing cancer outpatients continue to evolve during the COVID-19 pandemic, with recent innovations in technology, operations, and communication.

“We’ve tried a lot of new things to ensure optimal care for our patients,” said Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center (MSKCC) in New York. “We need to effectively utilize all resources at our disposal to keep in touch with our patients during this time.”

Dr. Traina described the approach to outpatient management used at MSKCC during a presentation at the AACR Virtual Meeting: COVID-19 and Cancer.
 

Four guiding principles

MSKCC has established four guiding principles on how to manage cancer patients during the pandemic: openness, safety, technology, and staffing.

Openness ensures that decisions are guided by clinical priorities to provide optimal patient care and allow for prioritization of clinical research and education, Dr. Traina said.

The safety of patients and staff is of the utmost importance, she added. To ensure safety in the context of outpatient care, several operational levers were developed, including COVID surge planning, universal masking and personal protective equipment guidelines, remote work, clinical levers, and new dashboards and communications.

Dr. Traina said data analytics and dashboards have been key technological tools used to support evidence-based decision-making and deliver care remotely for patients during the pandemic.

Staffing resources have also shifted to support demand at different health system locations.
 

Screening, cohorting, and telemedicine

One measure MSKCC adopted is the MSK Engage Questionnaire, a COVID-19 screening questionnaire assigned to every patient with a scheduled outpatient visit. After completing the questionnaire, patients receive a response denoting whether they need to come into the outpatient setting.

On the staffing side, clinic coordinators prepare appointments accordingly, based on the risk level for each patient.

“We also try to cohort COVID-positive patients into particular areas within the outpatient setting,” Dr. Traina explained. “In addition, we control flow through ambulatory care locations by having separate patient entrances and use other tools to make flow as efficient as possible.”

On the technology side, interactive dashboards are being used to model traffic through different buildings.

“These data and analytics are useful for operational engineering, answering questions such as (1) Are there backups in chemotherapy? and (2) Are patients seeing one particular physician?” Dr. Traina explained. “One important key takeaway is the importance of frequently communicating simple messages through multiple mechanisms, including signage, websites, and dedicated resources.”

Other key technological measures are leveraging telemedicine to convert inpatient appointments to a virtual setting, as well as developing and deploying a system for centralized outpatient follow-up of COVID-19-positive patients.

“We saw a 3,000% increase in telemedicine utilization from February 2020 to June 2020,” Dr. Traina reported. “In a given month, we have approximately 230,000 outpatient visits, and a substantial proportion of these are now done via telemedicine.”

Dr. Traina also noted that multiple organizations have released guidelines addressing when to resume anticancer therapy in patients who have been COVID-19 positive. Adherence is important, as unnecessary COVID-19 testing may delay cancer therapy and is not recommended.

During a live discussion, Louis P. Voigt, MD, of MSKCC, said Dr. Traina’s presentation provided “a lot of good ideas for other institutions who may be facing similar challenges.”

Dr. Traina and Dr. Voigt disclosed no conflicts of interest. No funding sources were reported.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

A novel community-based testing model has shown promise for colorectal cancer (CRC) screening during the COVID-19 pandemic.

The model is a socially distanced version of the Flu-Fecal Immunochemical Test (Flu-FIT) program, called Drive By Flu-FIT.

The original Flu-FIT program was designed to increase access to CRC screening by offering home FIT tests to patients at the time of their annual flu shots. The program has been shown to increase CRC screening in diverse populations.

Researchers wanted to determine if a drive-by version of Flu-FIT could counteract the decrease in CRC screening seen during the pandemic, so they conducted a pilot study.

“FIT-based CRC screening overcomes many of the challenges to colonoscopy-based screening due to COVID-19, [such as] not requiring an office visit, thereby overcoming workforce disruptions and many patient concerns,” explained investigator Armenta Washington of the University of Pennsylvania, Philadelphia.

Ms. Washington presented results with Drive By Flu-FIT at the AACR Virtual Meeting: COVID-19 and Cancer (Abstract S02-04).
 

About the study

The pilot study of Drive By Flu-FIT was conducted in collaboration with the Einstein Healthcare Network and Enon Tabernacle Baptist Church, the largest Baptist church in the Philadelphia region.

The program enrolled community members into one of three Drive By Flu-FIT events, which took place between October and November 2020. Eligible participants were aged 45-75 years and at average risk for CRC.

Interested candidates completed eligibility, registration, and demographic questionnaires electronically prior to enrollment.

Patients who enrolled watched a 7-minute CRC educational video and completed two questionnaires – one on CRC screening knowledge and one on screening intentions – before and after watching the video.

At the events, participants remained in their cars while physicians in personal protective equipment provided instructions on how to use the FIT and how to return the completed test to a medical collection box, as well as answering questions. Participants also had the option to receive a flu vaccine at the event.
 

Results

Among 335 registered participants, 80 (23.9%) did not ultimately attend an event, and 63 (18.8%) were deemed ineligible.

So 192 patients attended a Drive By Flu-FIT event and received a FIT (57.3%). Patients with symptoms/signs and family history of CRC were referred for colonoscopy.

Among patients who received a FIT, the mean age was 58.9 years, 60.4% were female, 93.8% self-identified as Black, 1.6% self-identified as Hispanic, 15.5% were uninsured, and 54.6% had been previously screened for CRC.

The researchers found that scores on the knowledge questionnaire increased after the video intervention (P = .0006), as did the intention to screen scores (P = .007).

“Baseline knowledge about CRC was high, with the exception of four items related to risk factors, frequency of FIT, Lynch syndrome, and the relationship between physical activity and the risk for CRC,” Ms. Washington explained. “All knowledge scores increased after the video, except for one item related to the early discovery of CRC and its relationship to survival.”

Among the 192 participants who received a FIT, 38 (19.7%) did not return it, 141 (73.4%) had a negative FIT result, and 13 (6.7%) had a positive FIT result and were referred to colonoscopy. The colonoscopy results are pending.

“Overall, we believe that this research shows that a social-distanced, Drive By Flu-FIT program is feasible, acceptable, and effective in engaging the community in CRC education and screening during the COVID-19 pandemic,” Ms. Washington said.

During a live discussion, Ms. Washington also noted that most patients opted to receive both the FIT test and the flu vaccine.

“This was certainly great work, especially with the outreach that was done,” commented moderator Ana Maria Lopez, MD, of Sidney Kimmel Medical College, Philadelphia.

The researchers plan to use the results of this pilot study to test and evaluate a Drive By COVID-19 vaccine-FIT model in spring 2021.

Ms. Washington and Dr. Lopez disclosed no conflicts of interest. The study was supported by the National Cancer Institute.  The FITs were donated by Polymedco Inc., and the flu vaccines were donated by the Philadelphia Public Health Department.

Marius Pharmaceuticals has submitted a new drug application (NDA) to the Food and Drug Administration for Kyzatrex, an oral testosterone replacement therapy (TRT).

With this NDA, the company is seeking approval for Kyzatrex as a treatment for adult men with primary and secondary hypogonadism, also known as testosterone deficiency. Marius has requested a priority review that, if accepted, would result in an anticipated 6-month review period.

Current treatment options for hypogonadal men consist of therapies with safety concerns, such as cardiovascular and metabolic risks, that make patient adherence to treatment very low.

Kyzatrex is a novel oral formulation of testosterone undecanoate administered twice daily in a soft gelatin capsule.

“TRT remains a therapeutic challenge because there are worrisome and conflicting data related to increased cardiovascular disease risk, which has special relevance to high-risk diabetic populations,” Paul S. Jellinger, MD, professor of clinical medicine at the University of Miami, told this news organization. Furthermore, “injectable depot testosterone may be associated with peak supraphysiological levels and a substantial increase in hemoglobin. Topical testosterone offers more stable levels without a peak and trough, but in some men achieving physiologic levels may be difficult.”

The NDA is supported by results from a 6-month treatment extension of the pivotal phase 3 MRS-TU-2019 study (NCT04467697). Final results from this study have not been presented, but the company wrote in a press release that the results will be published some time in 2021.

They further reported that Kyzatrex was well tolerated by patients, with more than 96% of study participants completing 90 days of treatment in the pivotal phase 3 study. Study patients achieved average testosterone levels in the normal range.

Across the pooled phase 3 trials, the most frequent treatment-related treatment-emergent adverse event (TEAE) was hypertension, and no serious TEAEs were considered treatment related.

“We are extremely proud to have generated compelling efficacy and safety data in our phase 3 trials,” said Om Dhingra, PhD, cofounder and CEO of Marius. “We look forward to continuing to work collaboratively with the FDA on the review of our application, and if approved, Kyzatrex has the potential to become the standard of care for the treatment of primary and secondary hypogonadism globally.”

“An oral [testosterone] preparation with steady state physiologic levels would be a welcome addition to our choices for therapy assuming, of course, the absence of adverse effects,” explained Dr. Jellinger. “However, the greater challenge of testosterone therapy is the appropriate selection of those suited for testosterone replacement therapy.”

The company also plans to submit a marketing authorization application with the European Medicines Agency in the first half of 2022.

Marius Pharmaceuticals has submitted a new drug application (NDA) to the Food and Drug Administration for Kyzatrex, an oral testosterone replacement therapy (TRT).

With this NDA, the company is seeking approval for Kyzatrex as a treatment for adult men with primary and secondary hypogonadism, also known as testosterone deficiency. Marius has requested a priority review that, if accepted, would result in an anticipated 6-month review period.

Current treatment options for hypogonadal men consist of therapies with safety concerns, such as cardiovascular and metabolic risks, that make patient adherence to treatment very low.

Kyzatrex is a novel oral formulation of testosterone undecanoate administered twice daily in a soft gelatin capsule.

“TRT remains a therapeutic challenge because there are worrisome and conflicting data related to increased cardiovascular disease risk, which has special relevance to high-risk diabetic populations,” Paul S. Jellinger, MD, professor of clinical medicine at the University of Miami, told this news organization. Furthermore, “injectable depot testosterone may be associated with peak supraphysiological levels and a substantial increase in hemoglobin. Topical testosterone offers more stable levels without a peak and trough, but in some men achieving physiologic levels may be difficult.”

The NDA is supported by results from a 6-month treatment extension of the pivotal phase 3 MRS-TU-2019 study (NCT04467697). Final results from this study have not been presented, but the company wrote in a press release that the results will be published some time in 2021.

They further reported that Kyzatrex was well tolerated by patients, with more than 96% of study participants completing 90 days of treatment in the pivotal phase 3 study. Study patients achieved average testosterone levels in the normal range.

Across the pooled phase 3 trials, the most frequent treatment-related treatment-emergent adverse event (TEAE) was hypertension, and no serious TEAEs were considered treatment related.

“We are extremely proud to have generated compelling efficacy and safety data in our phase 3 trials,” said Om Dhingra, PhD, cofounder and CEO of Marius. “We look forward to continuing to work collaboratively with the FDA on the review of our application, and if approved, Kyzatrex has the potential to become the standard of care for the treatment of primary and secondary hypogonadism globally.”

“An oral [testosterone] preparation with steady state physiologic levels would be a welcome addition to our choices for therapy assuming, of course, the absence of adverse effects,” explained Dr. Jellinger. “However, the greater challenge of testosterone therapy is the appropriate selection of those suited for testosterone replacement therapy.”

The company also plans to submit a marketing authorization application with the European Medicines Agency in the first half of 2022.

Marius Pharmaceuticals has submitted a new drug application (NDA) to the Food and Drug Administration for Kyzatrex, an oral testosterone replacement therapy (TRT).

With this NDA, the company is seeking approval for Kyzatrex as a treatment for adult men with primary and secondary hypogonadism, also known as testosterone deficiency. Marius has requested a priority review that, if accepted, would result in an anticipated 6-month review period.

Current treatment options for hypogonadal men consist of therapies with safety concerns, such as cardiovascular and metabolic risks, that make patient adherence to treatment very low.

Kyzatrex is a novel oral formulation of testosterone undecanoate administered twice daily in a soft gelatin capsule.

“TRT remains a therapeutic challenge because there are worrisome and conflicting data related to increased cardiovascular disease risk, which has special relevance to high-risk diabetic populations,” Paul S. Jellinger, MD, professor of clinical medicine at the University of Miami, told this news organization. Furthermore, “injectable depot testosterone may be associated with peak supraphysiological levels and a substantial increase in hemoglobin. Topical testosterone offers more stable levels without a peak and trough, but in some men achieving physiologic levels may be difficult.”

The NDA is supported by results from a 6-month treatment extension of the pivotal phase 3 MRS-TU-2019 study (NCT04467697). Final results from this study have not been presented, but the company wrote in a press release that the results will be published some time in 2021.

They further reported that Kyzatrex was well tolerated by patients, with more than 96% of study participants completing 90 days of treatment in the pivotal phase 3 study. Study patients achieved average testosterone levels in the normal range.

Across the pooled phase 3 trials, the most frequent treatment-related treatment-emergent adverse event (TEAE) was hypertension, and no serious TEAEs were considered treatment related.

“We are extremely proud to have generated compelling efficacy and safety data in our phase 3 trials,” said Om Dhingra, PhD, cofounder and CEO of Marius. “We look forward to continuing to work collaboratively with the FDA on the review of our application, and if approved, Kyzatrex has the potential to become the standard of care for the treatment of primary and secondary hypogonadism globally.”

“An oral [testosterone] preparation with steady state physiologic levels would be a welcome addition to our choices for therapy assuming, of course, the absence of adverse effects,” explained Dr. Jellinger. “However, the greater challenge of testosterone therapy is the appropriate selection of those suited for testosterone replacement therapy.”

The company also plans to submit a marketing authorization application with the European Medicines Agency in the first half of 2022.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

Intraoperative injection of calcium chloride into the four major atrial ganglionated plexi (GPs) reduced the incidence of early postoperative atrial fibrillation (POAF) in patients undergoing off-pump coronary artery bypass grafting (CABG) surgery, in a proof-of-concept study.

“[We] hypothesized that injecting [calcium chloride] into the major atrial GPs during isolated CABG can reduce the incidence of POAF by calcium-induced autonomic neurotoxicity,” wrote Huishan Wang, MD, of the General Hospital of Northern Theater Command in Shenyang, China, and colleagues. Their report was published in the Journal of the American College of Cardiology.

The single-center, sham-controlled, proof-of-concept study included 200 patients without a history of AF undergoing isolated, off-pump CABG surgery. Participants were randomized (1:1) to receive an injection of either 5% calcium chloride or 0.9% sodium chloride into the four major GPs during CABG.

Post surgery, patients were monitored for the occurrence of POAF using routine 12-lead ECG and 7-day continuous telemetry and Holter monitoring. The primary endpoint was the incidence of POAF lasting 30 seconds or longer through 7 days. Various secondary outcomes, including POAF burden and length of hospitalization, were also measured.

After analysis, the researchers found that 15 patients in the calcium chloride arm and 36 patients in the sodium chloride arm developed POAF during the first 7 days post CABG, corresponding to a POAF hazard reduction of 63% (hazard ratio, 0.37; 95% confidence interval, 0.21-0.64; P = .001) with no significant adverse effects observed among study patients.

The calcium chloride injection also resulted in reduced AF burden and lower rates of amiodarone and esmolol use to treat POAF; however, there was no difference in the length of hospitalization between the two groups. The incidences of nonsustained atrial tachyarrhythmia (less than 30 seconds) and atrial couplets were also significantly reduced in the calcium chloride group.

“We selected the 4 major atrial GPs as our targets because [of] their role in the initiation and maintenance of AF is more established than other cardiac neural plexi,” the researchers explained. “Interruption of the atrial neural network by Ca-mediated GP neurotoxicity may underlie the therapeutic effects.”
 

Is ‘nuisance’ arrhythmia worth targeting?

In an editorial accompanying the report, John H. Alexander, MD, MHS, wrote that intraoperative calcium chloride atrial ganglionic ablation can now be considered as an effective intervention to prevent POAF in patients undergoing cardiac surgery. “These investigators should be congratulated for studying post-operative atrial fibrillation in cardiac surgery,” he stated.

MDedge News

“However, this trial has two significant limitations. Firstly, it was conducted in a single center in a very homogeneous population; secondly, POAF, in and of itself, is largely a nuisance arrhythmia and hardly worth preventing, but is associated with a higher risk of other adverse outcomes,” Dr. Alexander, professor of medicine at Duke University, Durham, N.C., said in an interview.

“The unanswered question is whether preventing perioperative AF will prevent stroke, heart failure, and death,” he further explained. “Answering these questions would require a larger trial (or trials) with longer term (months to years) follow-up.”

Dr. Wang and colleagues acknowledged that the current study was underpowered for some secondary outcomes, such as length of hospitalization. They explained that a large sample size is needed to detect a difference in length of hospitalization, as well as other outcomes.

“Further studies are needed to confirm the safety and efficacy of calcium-induced atrial autonomic denervation in patients undergoing on-pump CABG and surgery for valvular heart disease,” they concluded.

The study was funded by the Provincial Key R & D Program in China. One author reported holding a U.S. patent related to the study. The remaining authors had no relevant relationships to disclose.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) evaluated Moderna’s COVID-19 vaccine as highly effective with a favorable safety profile, based on interim data from an ongoing phase 3 trial.

The panel acknowledged that further studies will be required post issuance of an Emergency Use Authorization (EUA) to collect additional data on the safety and effectiveness of the vaccine. A briefing document released by the FDA on Dec. 17, 2020, summarized interim results and included recommendations from VRBPAC on use of Moderna’s mRNA-1273 COVID-19 vaccine.

“On November 30, 2020, ModernaTX (the Sponsor) submitted an EUA request to FDA for an investigational COVID-19 vaccine (mRNA-1273) intended to prevent COVID-19,” the committee wrote.
 

The mRNA-1273 vaccine trial

Among 30,351 individuals aged 18 years and older, the efficacy, safety, and immunogenicity of the mRNA-1273 vaccine candidate was evaluated in a randomized, stratified, observer-blind, placebo-controlled phase 3 study. Participants were randomly assigned (1:1) to receive two injections of either 100 mcg of mRNA-1273 (n = 15,181) or saline placebo (n = 15,170) administered intramuscularly on day 1 and day 29.

The primary efficacy endpoint was efficacy of mRNA-1273 against PCR-confirmed COVID-19 with onset at least 14 days following the second dose. The primary safety endpoint was to characterize the safety of the vaccine following one or two doses.
 

Efficacy

Among 27,817 subjects included in the first interim analysis (data cutoff: Nov. 7, 2020), 5 cases of COVID-19 with onset at least 14 days after the second dose occurred among vaccine recipients and 90 case occurred among placebo recipients, corresponding to 94.5% vaccine efficacy (95% confidence interval, 86.5%-97.8%).

“Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across age groups, genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19,” they reported.

Data from the final scheduled analysis of the primary efficacy endpoint (data cutoff: Nov. 21, 2020; median follow-up of >2 months after dose 2), demonstrated 94.1% vaccine efficacy (95% confidence interval, 89.3%-96.8%), corresponding to 11 cases of COVID-19 in the vaccine group and 185 cases in the placebo group.

When stratified by age, the vaccine efficacy was 95.6% (95% CI, 90.6%-97.9%) for individuals 18-64 years of age and 86.4% (95% CI, 61.4%-95.5%) for those 65 years of age or older.

In addition, results from secondary analyses indicated benefit for mRNA-1273 in preventing severe COVID-19 cases, COVID-19 in those with prior SARS-CoV-2 infection, and infection after the first dose, but these data were not conclusive.
 

Safety

Among 30,350 subjects included in the first interim analysis (data cutoff: Nov. 11, 2020; median follow-up of 7 weeks post second dose), no specific safety concerns were observed that would prevent issuance of an EUA.

Additional safety data (data cutoff: Nov. 25, 2020; median follow-up of 9 weeks post second dose) were provided on Dec. 7, 2020, but did not change the conclusions from the first interim analysis.

The most common vaccine-related adverse reactions were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%).

“The frequency of serious adverse events (SAEs) was low (1.0% in the mRNA-1273 arm and 1.0% in the placebo arm), without meaningful imbalances between study arms,” they reported.

Myocardial infarction (0.03%), nephrolithiasis (0.02%), and cholecystitis (0.02%) were the most common SAEs that were numerically greater in the vaccine arm than the placebo arm; however, the small number of cases does not infer a casual relationship.

“The 2-dose vaccination regimen was highly effective in preventing PCR-confirmed COVID-19 occurring at least 14 days after receipt of the second dose,” the committee wrote. “[However], it is critical to continue to gather data about the vaccine even after it is made available under EUA.”

The associated phase 3 study was sponsored by ModernaTX.

SOURCE: FDA Briefing Document: Moderna COVID-19 Vaccine. FDA Vaccines and Related Biological Products Advisory Committee. Published Dec. 17, 2020.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) evaluated Moderna’s COVID-19 vaccine as highly effective with a favorable safety profile, based on interim data from an ongoing phase 3 trial.

The panel acknowledged that further studies will be required post issuance of an Emergency Use Authorization (EUA) to collect additional data on the safety and effectiveness of the vaccine. A briefing document released by the FDA on Dec. 17, 2020, summarized interim results and included recommendations from VRBPAC on use of Moderna’s mRNA-1273 COVID-19 vaccine.

“On November 30, 2020, ModernaTX (the Sponsor) submitted an EUA request to FDA for an investigational COVID-19 vaccine (mRNA-1273) intended to prevent COVID-19,” the committee wrote.
 

The mRNA-1273 vaccine trial

Among 30,351 individuals aged 18 years and older, the efficacy, safety, and immunogenicity of the mRNA-1273 vaccine candidate was evaluated in a randomized, stratified, observer-blind, placebo-controlled phase 3 study. Participants were randomly assigned (1:1) to receive two injections of either 100 mcg of mRNA-1273 (n = 15,181) or saline placebo (n = 15,170) administered intramuscularly on day 1 and day 29.

The primary efficacy endpoint was efficacy of mRNA-1273 against PCR-confirmed COVID-19 with onset at least 14 days following the second dose. The primary safety endpoint was to characterize the safety of the vaccine following one or two doses.
 

Efficacy

Among 27,817 subjects included in the first interim analysis (data cutoff: Nov. 7, 2020), 5 cases of COVID-19 with onset at least 14 days after the second dose occurred among vaccine recipients and 90 case occurred among placebo recipients, corresponding to 94.5% vaccine efficacy (95% confidence interval, 86.5%-97.8%).

“Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across age groups, genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19,” they reported.

Data from the final scheduled analysis of the primary efficacy endpoint (data cutoff: Nov. 21, 2020; median follow-up of >2 months after dose 2), demonstrated 94.1% vaccine efficacy (95% confidence interval, 89.3%-96.8%), corresponding to 11 cases of COVID-19 in the vaccine group and 185 cases in the placebo group.

When stratified by age, the vaccine efficacy was 95.6% (95% CI, 90.6%-97.9%) for individuals 18-64 years of age and 86.4% (95% CI, 61.4%-95.5%) for those 65 years of age or older.

In addition, results from secondary analyses indicated benefit for mRNA-1273 in preventing severe COVID-19 cases, COVID-19 in those with prior SARS-CoV-2 infection, and infection after the first dose, but these data were not conclusive.
 

Safety

Among 30,350 subjects included in the first interim analysis (data cutoff: Nov. 11, 2020; median follow-up of 7 weeks post second dose), no specific safety concerns were observed that would prevent issuance of an EUA.

Additional safety data (data cutoff: Nov. 25, 2020; median follow-up of 9 weeks post second dose) were provided on Dec. 7, 2020, but did not change the conclusions from the first interim analysis.

The most common vaccine-related adverse reactions were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%).

“The frequency of serious adverse events (SAEs) was low (1.0% in the mRNA-1273 arm and 1.0% in the placebo arm), without meaningful imbalances between study arms,” they reported.

Myocardial infarction (0.03%), nephrolithiasis (0.02%), and cholecystitis (0.02%) were the most common SAEs that were numerically greater in the vaccine arm than the placebo arm; however, the small number of cases does not infer a casual relationship.

“The 2-dose vaccination regimen was highly effective in preventing PCR-confirmed COVID-19 occurring at least 14 days after receipt of the second dose,” the committee wrote. “[However], it is critical to continue to gather data about the vaccine even after it is made available under EUA.”

The associated phase 3 study was sponsored by ModernaTX.

SOURCE: FDA Briefing Document: Moderna COVID-19 Vaccine. FDA Vaccines and Related Biological Products Advisory Committee. Published Dec. 17, 2020.

The Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) evaluated Moderna’s COVID-19 vaccine as highly effective with a favorable safety profile, based on interim data from an ongoing phase 3 trial.

The panel acknowledged that further studies will be required post issuance of an Emergency Use Authorization (EUA) to collect additional data on the safety and effectiveness of the vaccine. A briefing document released by the FDA on Dec. 17, 2020, summarized interim results and included recommendations from VRBPAC on use of Moderna’s mRNA-1273 COVID-19 vaccine.

“On November 30, 2020, ModernaTX (the Sponsor) submitted an EUA request to FDA for an investigational COVID-19 vaccine (mRNA-1273) intended to prevent COVID-19,” the committee wrote.
 

The mRNA-1273 vaccine trial

Among 30,351 individuals aged 18 years and older, the efficacy, safety, and immunogenicity of the mRNA-1273 vaccine candidate was evaluated in a randomized, stratified, observer-blind, placebo-controlled phase 3 study. Participants were randomly assigned (1:1) to receive two injections of either 100 mcg of mRNA-1273 (n = 15,181) or saline placebo (n = 15,170) administered intramuscularly on day 1 and day 29.

The primary efficacy endpoint was efficacy of mRNA-1273 against PCR-confirmed COVID-19 with onset at least 14 days following the second dose. The primary safety endpoint was to characterize the safety of the vaccine following one or two doses.
 

Efficacy

Among 27,817 subjects included in the first interim analysis (data cutoff: Nov. 7, 2020), 5 cases of COVID-19 with onset at least 14 days after the second dose occurred among vaccine recipients and 90 case occurred among placebo recipients, corresponding to 94.5% vaccine efficacy (95% confidence interval, 86.5%-97.8%).

“Subgroup analyses of the primary efficacy endpoint showed similar efficacy point estimates across age groups, genders, racial and ethnic groups, and participants with medical comorbidities associated with high risk of severe COVID-19,” they reported.

Data from the final scheduled analysis of the primary efficacy endpoint (data cutoff: Nov. 21, 2020; median follow-up of >2 months after dose 2), demonstrated 94.1% vaccine efficacy (95% confidence interval, 89.3%-96.8%), corresponding to 11 cases of COVID-19 in the vaccine group and 185 cases in the placebo group.

When stratified by age, the vaccine efficacy was 95.6% (95% CI, 90.6%-97.9%) for individuals 18-64 years of age and 86.4% (95% CI, 61.4%-95.5%) for those 65 years of age or older.

In addition, results from secondary analyses indicated benefit for mRNA-1273 in preventing severe COVID-19 cases, COVID-19 in those with prior SARS-CoV-2 infection, and infection after the first dose, but these data were not conclusive.
 

Safety

Among 30,350 subjects included in the first interim analysis (data cutoff: Nov. 11, 2020; median follow-up of 7 weeks post second dose), no specific safety concerns were observed that would prevent issuance of an EUA.

Additional safety data (data cutoff: Nov. 25, 2020; median follow-up of 9 weeks post second dose) were provided on Dec. 7, 2020, but did not change the conclusions from the first interim analysis.

The most common vaccine-related adverse reactions were injection site pain (91.6%), fatigue (68.5%), headache (63.0%), muscle pain (59.6%), joint pain (44.8%), and chills (43.4%).

“The frequency of serious adverse events (SAEs) was low (1.0% in the mRNA-1273 arm and 1.0% in the placebo arm), without meaningful imbalances between study arms,” they reported.

Myocardial infarction (0.03%), nephrolithiasis (0.02%), and cholecystitis (0.02%) were the most common SAEs that were numerically greater in the vaccine arm than the placebo arm; however, the small number of cases does not infer a casual relationship.

“The 2-dose vaccination regimen was highly effective in preventing PCR-confirmed COVID-19 occurring at least 14 days after receipt of the second dose,” the committee wrote. “[However], it is critical to continue to gather data about the vaccine even after it is made available under EUA.”

The associated phase 3 study was sponsored by ModernaTX.

SOURCE: FDA Briefing Document: Moderna COVID-19 Vaccine. FDA Vaccines and Related Biological Products Advisory Committee. Published Dec. 17, 2020.

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

The Pfizer COVID-19 vaccine was shown to be highly effective in a large trial, but clinicians will be waiting and watching for reactions and adverse events in their vaccinated patients.

A two-dose regimen of the BNT162b2 mRNA COVID-19 vaccine was found to be safe and 95% effective in preventing SARS-CoV-2 infection in persons aged 16 years and older, according to an ongoing phase 2/3 trial. Pfizer and BioNTech published safety and efficacy results from the landmark global phase 1/2/3 trial of their COVID-19 vaccine candidate in the New England Journal of Medicine .

“We previously reported phase 1 safety and immunogenicity results from clinical trials of the vaccine candidate BNT162b2,” lead author Fernando P. Polack, MD, of Vanderbilt University, Nashville, Tenn., and colleagues wrote. “This data set and [present] trial results are the basis for an application for emergency-use authorization,” they explained.
 

The BNT162b2 vaccine trial

Among 43,448 individuals aged 16 years and older, the efficacy, safety, and immunogenicity of the BNT162b2 vaccine candidate was evaluated in a continuous phase 1/2/3 study. Participants were randomly assigned (1:1) to receive two injections of either 30 mcg of BNT162b2 (n = 21,720) or saline placebo (n = 21,728) administered intramuscularly 21 days apart. The safety evaluation, where subjects were monitored 30 minutes post vaccination for acute reactions, was observer blinded.

Eligibility criteria included healthy individuals or those with stable chronic medical conditions, including viral hepatitis B and C, as well as human immunodeficiency virus. Persons with a diagnosis of an immunocompromising condition, those receiving immunosuppressive therapy, and individuals with a medical history of COVID-19 were excluded.

The first primary endpoint was efficacy of BNT162b2 against laboratory-confirmed COVID-19 with onset at least 7 days following the second dose. The primary safety endpoint was local and systemic reactions occurring within 7 days post injection of BNT162b2 or placebo.
 

Safety

“At the data cutoff date of Oct. 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set,” the authors wrote.

Among these participants, 83% were White, 28% were Hispanic or Latinx, and 9% were Black or African American; 49% of subjects were female and the median age was 52 years, with 42% over aged 55 years.

Overall, BNT162b2 had a favorable safety profile. Mild to moderate pain at the injection site within 7 days after the injection was the most frequently reported local reaction (<1% across all age groups reported severe pain). Most local reactions resolved within 1-2 days and no grade 4 reactions were reported.

The investigators reported: “Fever (temperature, ≥38° C) was reported after the second dose by 16% of younger vaccine recipients and by 11% of older recipients. Only 0.2% of vaccine recipients and 0.1% of placebo recipients reported fever (temperature, 38.9-40° C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.”

BNT162b2 recipients had more injection-site pain than those receiving the placebo. After the first and second doses, younger recipients (under 55 years) had more pain at the injection site (83 vs. 14 and 78 vs. 12 events, respectively), redness (5 vs. 1 and 6 vs. 1), and swelling (6 vs. 0 and 6 vs. 0), compared with placebo recipients.

The same trend was observed for patients aged over 55 years, with vaccine recipients reporting more pain at the injection site (71 vs. 9 and 66 vs. 8 events, respectively), redness (5 vs. 1 and 7 vs. 1), and swelling (7 vs. 1 and 7 vs. 1) than placebo recipients.

Pain was less common overall among vaccine recipients aged over 55 years (71% reported pain after the first dose; 66% post second dose) than among younger vaccine recipients (83% post first dose; 78% post second dose).

The most common systemic events following the second dose were fatigue and headache, which occurred in 59% and 52% of younger vaccine recipients and 51% and 39% of older vaccine recipients, respectively. But fatigue and headache were also reported by participants in the placebo group (23% and 24%, respectively, post second dose, among younger vaccine recipients; 17% and 14% among older recipients).

The incidence of serious adverse events was low and similar in the vaccine (0.6%) and placebo (0.5%) arms. Severe systemic events occurred in 2% or less of vaccine recipients following either dose, except for fatigue (3.8%) and headache (2.0%) post second dose. No deaths were considered to be vaccine or placebo related.

“The safety appears comparable to other vaccines, but the relatively short period of observation, 2 months, and the relatively small number of subjects who have received the vaccine (less than 30,000), compared to the hundreds of millions likely to ultimately receive the vaccine, precludes conclusions regarding the potential for rare long term adverse effects,” David L. Bowton, MD, FCCP, a pulmonologist and professor emeritus of critical care anesthesiology at Wake Forest University, Winston-Salem, N.C., said in an interview. “Clinicians should be aware of the risk of anaphylactic reactions and discuss it with their patients [who have] a history of these reactions.”
 

Efficacy

Among 36,523 subjects without evidence of existing or prior COVID-19 infection, 8 cases of COVID-19 with onset at least 7 days after the second dose were seen among vaccine recipients and 162 among placebo recipients, corresponding to 95.0% vaccine efficacy (95% credible interval, 90.3%-97.6%).

“Supplemental analyses indicated that vaccine efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population,” the authors wrote.

Between the first and second doses, 39 cases of COVID-19 were observed among BNT162b2 recipients and 82 cases among placebo recipients, corresponding to 52% vaccine efficacy during the 21-day interval (95% CI, 29.5%-68.4%) suggesting early protection may begin as soon as 12 days after the first injection.

“This is an incredible achievement given that an effective vaccine has never been developed and approved for use in such a short timeframe,” Dr. Bowton explained. “That the vaccine is highly effective in reducing the incidence of symptomatic COVID-19 seems incontrovertible.”

“This vaccine has shockingly amazing efficacy and is well tolerated, and the results are beyond even optimistic projections,” Douglas S. Paauw, MD, of the University of Washington, Seattle, said in an interview.
 

Questions remain

“It is not yet known if the vaccine prevents asymptomatic infections, with their attendant risk of contagion, as rates of seroconversion of trial participants against betacoronavirus nucleoproteins not included in the vaccine has not been reported,” Dr. Bowton commented.

“Common questions our patients will ask us remain unanswered for now, [including] how long will the protection last, is it safe in pregnant women, and does it prevent asymptomatic infection,” Dr. Paauw explained. “We do not know everything about longer term side effects, but the benefits of this vaccine appear to outweigh the risks of the vaccine.”

The researchers noted these and other limitations in their report, acknowledging that longer follow-up is needed to evaluate long-term safety of the vaccine.

This study was supported by BioNTech and Pfizer. Several authors disclosed financial relationships with Pfizer and other pharmaceutical companies outside the submitted work. Dr. Bowton and Dr. Paauw had no conflicts to disclose.

SOURCE: Polack FP et al. N Engl J Med. 2020 Dec 10. doi: 10.1056/NEJMoa2034577
 

A real-world study has revealed factors associated with longer overall survival (OS) in patients who receive cabozantinib to treat heavily pretreated, metastatic renal cell carcinoma (mRCC).

Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.

These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.

“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.

The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.

The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.

The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.

The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.

The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).

Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.

Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).

The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).

Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).

“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.

“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).

“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.

Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.

This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.

SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.

A real-world study has revealed factors associated with longer overall survival (OS) in patients who receive cabozantinib to treat heavily pretreated, metastatic renal cell carcinoma (mRCC).

Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.

These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.

“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.

The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.

The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.

The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.

The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.

The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).

Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.

Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).

The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).

Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).

“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.

“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).

“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.

Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.

This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.

SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.

A real-world study has revealed factors associated with longer overall survival (OS) in patients who receive cabozantinib to treat heavily pretreated, metastatic renal cell carcinoma (mRCC).

Starting cabozantinib at 60 mg/day, prior nephrectomy, favorable- or intermediate-risk disease, and body mass index of 25 kg/m2 or higher were all significantly associated with better OS.

These findings were based on data from the early access program of the CABOREAL study and were recently published in the European Journal of Cancer.

“The CABOREAL study describes cabozantinib use in a real-life setting in the largest unselected population to date of patients with mRCC,” lead author Laurence Albiges, MD, PhD, of the Gustave Roussy Cancer Center in Villejuif, France, and colleagues wrote.

The retrospective study enrolled 410 patients with mRCC who were treated with at least one dose of cabozantinib between September 2016 and February 2018. Clinical data were collected from medical records at 26 oncology centers in France.

The researchers evaluated the real-world use of cabozantinib, including duration of therapy, treatment discontinuations, and dose changes. OS and predictive factors of OS were assessed as well.

The median age of study participants was 63.0 years (range, 56.0-70.0 years). Roughly a third of patients (33.4%) received two prior lines of therapy (33.4%), and 41.2% received three or more lines of therapy before cabozantinib. Overall, 85.6% of patients had clear cell histology.

The median duration of cabozantinib treatment was 7.6 months (range, 3.2-15.7 months). The starting dose was 60 mg, 40 mg, and 20 mg in 70.9%, 26.7%, and 2.0% of patients, respectively.

The dose was decreased in 57.0% of patients, 58.7% required a dose modification, and 15.6% required a modified dose schedule. The median average daily dose was 40.0 mg (range, 13.9-60.0 mg).

Adverse events were the main reason for dose modification or treatment interruption. In all, 92.5% of patients had a modification because of an adverse event, and 85.0% had an interruption because of an adverse event.

Upon permanent discontinuation of cabozantinib, more than half of patients (54.4%) received subsequent therapy, including nivolumab (47.8%), axitinib (21.7%), and everolimus (19.0%).

The median OS was 14.4 months (95% confidence interval, 12.4-16.2 months), and the 1-year OS rate was 56.5% (95% CI, 51.5-61.2%).

Factors significantly associated with longer OS included cabozantinib initiation at 60 mg/day (P = .0486), prior nephrectomy (P = .0109), favorable or intermediate risk according to the International Metastatic RCC Database Consortium (P < .0001), and body mass index of 25 kg/m2 or higher (P = .0021).

“We report, for the first time, that the daily dose of 60 mg cabozantinib at initiation is an independent predictive factor of OS in a multivariate analysis,” the researchers wrote.

“It is interesting to see real-world studies like this to help to widen our understanding of how to utilize drugs like cabozantinib,” commented Simon Crabb, MBBS, PhD, of the University of Southampton (England).

“In general, we would expect a less favorable prognosis in patients with non-clear cell histology, likely in part part due to the underlying biology of the disease,” he added.

Dr. Albiges and colleagues acknowledged that the retrospective design and lack of a prospective safety evaluation were two key limitations of their study. However, the authors maintain that the reported cabozantinib use and exposure rates are indicative of the real-world setting.

This study was sponsored by Ipsen. Several authors disclosed financial relationships with Amgen, Astellas Pharma, AstraZeneca, Bristol-Myers Squibb, Exelixis, Ipsen, and numerous other companies. Dr. Crabb reported having no conflicts of interest related to this work.

SOURCE: Albiges L et al. Eur J Cancer. 2020 Nov 27. doi: 10.1016/j.ejca.2020.09.030.