Background: The ability to independently perform daily activities is highly valued by patients, yet it is commonly impaired in older adults after hospitalization for MI. Risk of functional decline in this population is not well understood, but may relate to reduced mobility while hospitalized.

While in-hospital mobility is predictive of future functional decline in this population, this observational study cannot establish whether attempts to improve mobility in hospitalized patients will prevent future functional decline.

Bottom line: Lower performance on the Timed “Up and Go” test of mobility among older patients hospitalized for MI is associated with functional decline 6 months after hospitalization.

Citation: Hajduk AM et al. Association between mobility measured during hospitalization and functional outcomes in older adults with acute myocardial infarction in the SILVER-AMI study. JAMA Intern Med. 2019 Oct 7. doi: 10.1001/jamainternmed.2019.4114.

Dr. Gerstenberger is a hospitalist and clinical assistant professor of medicine at the University of Utah, Salt Lake City.

Background: The ability to independently perform daily activities is highly valued by patients, yet it is commonly impaired in older adults after hospitalization for MI. Risk of functional decline in this population is not well understood, but may relate to reduced mobility while hospitalized.

While in-hospital mobility is predictive of future functional decline in this population, this observational study cannot establish whether attempts to improve mobility in hospitalized patients will prevent future functional decline.

Bottom line: Lower performance on the Timed “Up and Go” test of mobility among older patients hospitalized for MI is associated with functional decline 6 months after hospitalization.

Citation: Hajduk AM et al. Association between mobility measured during hospitalization and functional outcomes in older adults with acute myocardial infarction in the SILVER-AMI study. JAMA Intern Med. 2019 Oct 7. doi: 10.1001/jamainternmed.2019.4114.

Dr. Gerstenberger is a hospitalist and clinical assistant professor of medicine at the University of Utah, Salt Lake City.

Background: The ability to independently perform daily activities is highly valued by patients, yet it is commonly impaired in older adults after hospitalization for MI. Risk of functional decline in this population is not well understood, but may relate to reduced mobility while hospitalized.

While in-hospital mobility is predictive of future functional decline in this population, this observational study cannot establish whether attempts to improve mobility in hospitalized patients will prevent future functional decline.

Bottom line: Lower performance on the Timed “Up and Go” test of mobility among older patients hospitalized for MI is associated with functional decline 6 months after hospitalization.

Citation: Hajduk AM et al. Association between mobility measured during hospitalization and functional outcomes in older adults with acute myocardial infarction in the SILVER-AMI study. JAMA Intern Med. 2019 Oct 7. doi: 10.1001/jamainternmed.2019.4114.

Dr. Gerstenberger is a hospitalist and clinical assistant professor of medicine at the University of Utah, Salt Lake City.

A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.

The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.

The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.

Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.

At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.

But at the latest meeting, the working group proposed that the trial should live on.

One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.

The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.

The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.

The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.

This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.

“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.

Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”

Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.

“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.

That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.

“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.

TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”

“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
 

A drop in study power

The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.

Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.

Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.

The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”

Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.

The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.

Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:

• Distant metastases
• At least one lymph node macrometastasis
• Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
• Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.

In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.

Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.

Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”

Dr. Kopans says that is a problem.

“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.

Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.

On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.

However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.

The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.

The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.

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

A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.

The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.

The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.

Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.

At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.

But at the latest meeting, the working group proposed that the trial should live on.

One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.

The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.

The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.

The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.

This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.

“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.

Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”

Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.

“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.

That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.

“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.

TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”

“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
 

A drop in study power

The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.

Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.

Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.

The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”

Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.

The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.

Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:

• Distant metastases
• At least one lymph node macrometastasis
• Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
• Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.

In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.

Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.

Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”

Dr. Kopans says that is a problem.

“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.

Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.

On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.

However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.

The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.

The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.

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

A controversial, big-budget breast cancer screening trial that has been chronically unable to attract enough female participants since its debut in 2017 got a vote of confidence from a special working group of the National Cancer Institute (NCI) on March 17.

The Tomosynthesis Mammography Imaging Screening Trial (TMIST) should continue, but with modification, the expert group concluded in its report.

The randomized trial, with an estimated cost of $100 million, compares two kinds of mammography screenings for breast cancer in healthy women. One group of patients is screened with digital breast tomosynthesis, also known as 3-D mammography; the other is screened with the older, less expensive 2-D digital technology.

Tomosynthesis is already considered superior in detecting small cancers and reducing callbacks and is increasingly being used in the real world, leading some experts in the field to say that TMIST is critically hampered by women’s and radiologists’ preference for 3-D mammography.

At a meeting of an NCI advisory board in September 2020, there was a suggestion that the federal agency may kill the trial.

But at the latest meeting, the working group proposed that the trial should live on.

One of the main problems with the trial has been recruitment; the recommended changes discussed at the meeting include reducing the number of women needed in the study (from 165,000 to 102,000), which would allow patient “accrual to be completed more quickly,” the working group noted. In addition, the target date for completing patient accrual would be moved to 2023, 3 years after the original completion date of 2020.

The group’s recommendations now go to NCI staff for scientific review. The NCI will then decide about implementing the proposed changes.

The trial, which is the NCI’s largest and most expensive screening study, has never come close to targeted monthly enrollment. It was enrolling fewer than 1,500 patients per month over a 2-year period, instead of the projected 5,500 per month, Philip Castle, PhD, MPH, director of the NCI’s Division of Cancer Prevention, said last year. He called for a review of TMIST’s “feasibility and relevance” in view of the increasing use of tomosynthesis in the United States, as well as other factors.

The new technology has been “rapidly adopted” by facilities in North America, the working group noted. As of December 2020, approximately 74% of breast cancer screening clinics in the United States had at least one tomosynthesis or 3-D system; 42% of the mammography machines were 3-D.

This trend of increasing use of 3-D machines might be too much for TMIST to surmount, said Nancy Davidson, MD, of the Fred Hutchinson Cancer Research Center, in Seattle, who chaired the working group.

“We are worried the challenges [to patient accrual] may persist due to the increasing adoption of three-dimensional breast tomosynthesis in the United States over time,” she said during the working group’s virtual presentation of the report to the NCI’s Clinical Trials and Translational Research Advisory Committee.

Committee member Smita Bhatia, MD, PhD, of the University of Alabama at Birmingham, wondered, “What are the ongoing barriers that [TMIST investigators] are going to face beside recruitment?”

Dr. Davidson answered by speaking, again, about market penetration of tomosynthesis machines and suggested that the recruitment problems and the availability of 3-D mammography are intertwined.

“Is this a technology that has or will arrive, at which point it may not be very easy to put the genie back in the bottle?” she asked.

That question has already been answered – widespread use of tomosynthesis is here to stay, argued Daniel Kopans, MD, of Harvard Medical School, Boston, who invented digital breast tomosynthesis but no longer benefits financially from his invention because the patent has expired.

“The horse is out of the barn,” Dr. Kopans said in an interview. By the time the study results are available, digital mammography will be a tool of the past, he said.

TMIST is a trial “that should never have been started in the first place, and it’s failing,” he said. “I was hoping they [the NCI] would say, ‘Let’s stop this because there’s not enough accrual.’ But it looks like they’re not.”

“TMIST is a waste of money,” said Dr. Kopans, repeating a criticism he has made in the past.
 

A drop in study power

The new recommendations for TMIST come about 1 year after Medscape Medical News reported that the study was lagging in enrollment of both patients and participating sites/physicians.

Last year, two TMIST study investigators said it had been difficult enlisting sites, in part because many radiologists and facilities – informed by their experience and previous research results – already believe that the 3-D technology is superior.

Currently, most 3-D systems are used in conjunction with 2-D. First, two static images of the breast are taken (2-D), and then the unit moves in an arc, taking multiple images of the breast (3-D). Thus, 3-D is widely described as allowing clinicians to flip through the images like “pages in a book” and as offering a superior read of the breast.

The NCI working group concedes that “there is evidence that screening utilizing tomosynthesis may reduce recall rates and improve cancer detection,” but it says the trial is needed to address “questions that still remain regarding the overall benefit to patients.”

Furthermore, tomosynthesis “may carry higher out-of-pocket costs for women and is more labor intensive and costly for health care systems in that it requires about twice as much reader time for interpretation,” the working group said.

The “main hypothesis of TMIST” is that “tomosynthesis will decrease the cumulative incidence of advanced breast cancers, a surrogate for mortality, compared to standard digital mammography,” posits the group.

Advanced breast cancer is defined in TMIST as invasive breast cancers that meet any of the following criteria:

• Distant metastases
• At least one lymph node macrometastasis
• Tumor size >1 cm and triple-negative or positive for human epidermal growth factor receptor
• Tumor size ≥ 20 mm unless of pure mucinous or other favorable histologies.

In the original study design, the sample size was estimated to be sufficient to provide 90% power to detect a 20% relative reduction in the proportion of advanced cancers in the intervention arm (tomosynthesis, or 3-D) compared to the control arm (digital mammography, or 2-D) 4.5 years from randomization.

Now, with fewer patients and a revised analytic approach, the study’s statistical power will be decreased to 80% from the original 90%.

Also, an advanced cancer is counted “if it occurs at any time while the participant is on study.”

Dr. Kopans says that is a problem.

“That is a huge mistake, since digital breast tomosynthesis cannot impact prevalent cancers. They are already there. This means that their ‘power calculation’ is wrong, and they won’t have the power that they are claiming,” he said.

Dr. Kopans explained that the first screen in TMIST will have “no effect on the number of advanced cancers.” That’s because the cancers will have already grown enough to become advanced, he said.

On the other hand, an initial screening might detect and thus lead to the removal of nonadvanced, smaller cancers, which, had they not been detected and removed, would have grown to become advanced cancers by the next year. Thus, the screenings done after the first year are the ones that potentially prove the effect of the intervention.

However, the working group report says that changes to the study will not affect anything other than a 10% reduction in the study’s power.

The working group is concerned about TMIST going on for years and years. For that reason, they recommended that the NCI establish “strict criteria for termination of the study” if accrual goals are not met. However, those parameters have not been developed, and it was not part of the study group’s mission to establish them.

The working group was sponsored by the NCI. Dr. Kopans reports consulting with DART Imaging in China.

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

The early phase of the COVID-19 pandemic was an extraordinarily uncertain, yet innovative, time.¹ Few data describe site-level effects of the many adaptations made to deal with surging case numbers, but studies of larger hospital referral regions (HRR) provide important clues.

In this issue of the Journal of Hospital Medicine, Janke et al² describe how availability of hospital resources in a region relate to COVID-19 mortality between March and June 2020.The authors’ findings suggest that, at least for early periods of the pandemic, having more intensive care unit (ICU), hospital bed, or nursing capacity per COVID-19 case was associated with lower mortality, while physician availability was not. Moreover, months later there were no associations between service or physician availability and HRR COVID-19 mortality. The authors observed variations in mortality rates in places commonly thought to have been overwhelmed early in the pandemic (April 2020), as well as in cities (Boston, Philadelphia, Hartford, Detroit, and Camden, New Jersey) that had a less prominent place in the news at that time.

Larger hospitals tend to have the resources necessary to make wholesale changes when preparing for a pandemic wave. Thus, Janke et al’s results may not have fully captured the pandemic’s potential impact in settings with fewer resources or in smaller hospitals, which are currently being overwhelmed.³

The number of cases and hospitalizations in this third wave of COVID-19 continues to rise, and the strain on healthcare resources has been felt across entire regions, making the results of this study even more salient. Hospital outcomes for COVID-19 are sensitive to limitations in physical locations (number of beds, ICU capacity) and nursing capacity. Nurses more often are assigned specifically to a bed or unit, and the number of patients per nurse is limited by state or local statute. Innovations such as COVID-19 field hospitals or redeploying existing beds (eg, converting postanesthesia care units to ICUs) offset physically constrained resources.⁴ On the other hand, lower acuity in this phase of the pandemic (eg, fewer ICU admissions) and shorter lengths of stay may produce higher turnover, producing more workforce stress, regardless of bed availability.

Early work of our COVID-19 collaborative⁵ suggests that the focus on localizing patients to geographic units or teams has given way to strategies that utilize more flexible team and bed-finding approaches. Clinical care has evolved to focus on more aggressive discharge strategies, with remote monitoring and hospital-at-home capabilities. Overall, the pandemic is providing fodder for future studies examining interaction between case volumes, physician and nurse availability, and evolution in clinical care practices. Most critically, it provides an opportunity to study health system flexibility and robustness with a lens that incorporates a view of the hospital and its surroundings as tightly related parts of care delivery. Because if there is one thing the pandemic is teaching us, it is that, more than ever, no hospital can be an island unto itself, and each hospital is part of a larger ecosystem where rising tides are felt throughout.

The early phase of the COVID-19 pandemic was an extraordinarily uncertain, yet innovative, time.¹ Few data describe site-level effects of the many adaptations made to deal with surging case numbers, but studies of larger hospital referral regions (HRR) provide important clues.

In this issue of the Journal of Hospital Medicine, Janke et al² describe how availability of hospital resources in a region relate to COVID-19 mortality between March and June 2020.The authors’ findings suggest that, at least for early periods of the pandemic, having more intensive care unit (ICU), hospital bed, or nursing capacity per COVID-19 case was associated with lower mortality, while physician availability was not. Moreover, months later there were no associations between service or physician availability and HRR COVID-19 mortality. The authors observed variations in mortality rates in places commonly thought to have been overwhelmed early in the pandemic (April 2020), as well as in cities (Boston, Philadelphia, Hartford, Detroit, and Camden, New Jersey) that had a less prominent place in the news at that time.

Larger hospitals tend to have the resources necessary to make wholesale changes when preparing for a pandemic wave. Thus, Janke et al’s results may not have fully captured the pandemic’s potential impact in settings with fewer resources or in smaller hospitals, which are currently being overwhelmed.³

The number of cases and hospitalizations in this third wave of COVID-19 continues to rise, and the strain on healthcare resources has been felt across entire regions, making the results of this study even more salient. Hospital outcomes for COVID-19 are sensitive to limitations in physical locations (number of beds, ICU capacity) and nursing capacity. Nurses more often are assigned specifically to a bed or unit, and the number of patients per nurse is limited by state or local statute. Innovations such as COVID-19 field hospitals or redeploying existing beds (eg, converting postanesthesia care units to ICUs) offset physically constrained resources.⁴ On the other hand, lower acuity in this phase of the pandemic (eg, fewer ICU admissions) and shorter lengths of stay may produce higher turnover, producing more workforce stress, regardless of bed availability.

Early work of our COVID-19 collaborative⁵ suggests that the focus on localizing patients to geographic units or teams has given way to strategies that utilize more flexible team and bed-finding approaches. Clinical care has evolved to focus on more aggressive discharge strategies, with remote monitoring and hospital-at-home capabilities. Overall, the pandemic is providing fodder for future studies examining interaction between case volumes, physician and nurse availability, and evolution in clinical care practices. Most critically, it provides an opportunity to study health system flexibility and robustness with a lens that incorporates a view of the hospital and its surroundings as tightly related parts of care delivery. Because if there is one thing the pandemic is teaching us, it is that, more than ever, no hospital can be an island unto itself, and each hospital is part of a larger ecosystem where rising tides are felt throughout.

The early phase of the COVID-19 pandemic was an extraordinarily uncertain, yet innovative, time.¹ Few data describe site-level effects of the many adaptations made to deal with surging case numbers, but studies of larger hospital referral regions (HRR) provide important clues.

In this issue of the Journal of Hospital Medicine, Janke et al² describe how availability of hospital resources in a region relate to COVID-19 mortality between March and June 2020.The authors’ findings suggest that, at least for early periods of the pandemic, having more intensive care unit (ICU), hospital bed, or nursing capacity per COVID-19 case was associated with lower mortality, while physician availability was not. Moreover, months later there were no associations between service or physician availability and HRR COVID-19 mortality. The authors observed variations in mortality rates in places commonly thought to have been overwhelmed early in the pandemic (April 2020), as well as in cities (Boston, Philadelphia, Hartford, Detroit, and Camden, New Jersey) that had a less prominent place in the news at that time.

Larger hospitals tend to have the resources necessary to make wholesale changes when preparing for a pandemic wave. Thus, Janke et al’s results may not have fully captured the pandemic’s potential impact in settings with fewer resources or in smaller hospitals, which are currently being overwhelmed.³

The number of cases and hospitalizations in this third wave of COVID-19 continues to rise, and the strain on healthcare resources has been felt across entire regions, making the results of this study even more salient. Hospital outcomes for COVID-19 are sensitive to limitations in physical locations (number of beds, ICU capacity) and nursing capacity. Nurses more often are assigned specifically to a bed or unit, and the number of patients per nurse is limited by state or local statute. Innovations such as COVID-19 field hospitals or redeploying existing beds (eg, converting postanesthesia care units to ICUs) offset physically constrained resources.⁴ On the other hand, lower acuity in this phase of the pandemic (eg, fewer ICU admissions) and shorter lengths of stay may produce higher turnover, producing more workforce stress, regardless of bed availability.

Early work of our COVID-19 collaborative⁵ suggests that the focus on localizing patients to geographic units or teams has given way to strategies that utilize more flexible team and bed-finding approaches. Clinical care has evolved to focus on more aggressive discharge strategies, with remote monitoring and hospital-at-home capabilities. Overall, the pandemic is providing fodder for future studies examining interaction between case volumes, physician and nurse availability, and evolution in clinical care practices. Most critically, it provides an opportunity to study health system flexibility and robustness with a lens that incorporates a view of the hospital and its surroundings as tightly related parts of care delivery. Because if there is one thing the pandemic is teaching us, it is that, more than ever, no hospital can be an island unto itself, and each hospital is part of a larger ecosystem where rising tides are felt throughout.

Several studies have examined variation in outcomes of patients with COVID-19, with emphasis on hospital-level factors such as geographic location, workforce and resource availability, and COVID-19 community prevalence.^1,2 Block et al¹ examine variation in COVID-19 mortality across 117 US hospitals, exploring whether COVID-19 admission volume was associated with mortality. While their results suggest that patients admitted to hospitals in the highest quintiles of COVID-19 caseload had higher odds of in-hospital death, the authors were not able to fully adjust for severity of illness, tempering our ability to draw conclusions. However, their finding is consistent with work showing that emergency department crowding and high hospital utilization are associated with excess mortality.

Block et al¹ also found variation within quintiles of COVID-19 burden, suggesting that other hospital-level factors are influencing their performance. In response to the initial surge of COVID-19 in the United States, hospitals and healthcare systems made rapid, often major, adjustments to provide care. Four interdependent components contribute to an effective surge response: system, space, staff, and supplies. Although all four components are important, effective systems are critical. Systems domains include command, or the creation of leadership teams throughout the organization; control, or management, of infrastructure; communication of rapid, comprehensible messages internally and externally; coordination of resources across departments and professions; and continuity of operations.³ Little is known about how well hospitals have implemented these systems components throughout the pandemic, and while Janke et al² examined the association of resources with outcomes, neither their study nor Block et al’s was able to account for other organizational or systems-based aspects of surge response.

Studies that help us understand the organizational factors and care-delivery adaptations associated with better outcomes for patients with COVID-19 are sorely needed, and could provide important insights for organizational adaptation and change more generally. Janke et al² and, in their accompanying editorial, Auerbach and Greysen,⁴ call for “innovative protocols” and “flexibility” to meet the needs of high-demand, novel situations. However, organizations’ ability to innovate and adapt relies on their relationships and teamwork capability.

The relational infrastructure within an organization provides the basis for effective teamwork, facilitating other aspects of an organization’s surge response and ability to adapt. Relationships characterized by trust and mindfulness create a context of psychological safety that encourages sharing new ideas, and enable teams to rapidly make sense of new situations and create shared understandings that facilitate effective action: improvising, adapting, and learning. Trust and psychological safety are especially important during crises, as decision-making tends to evolve toward top-down processes in times of crisis.

Hospitals currently collect few data that speak to relationships and teamwork, limiting our ability to study these vital organizational characteristics and their role in the larger COVID-19 response. Surveys related to patient safety culture or provider wellness and burnout are likely the only data regularly collected by hospitals. Expanding these data to include measures of relational infrastructure will create more robust data not only to conduct research regarding organizational factors that are associated with patient outcomes, but also to allow health systems to improve relationships and teaming as a means of improving outcomes. Examples include relational coordination,⁵ relationships,⁶and learning scales.⁷

The hospitals to which patients are admitted make a difference in patient survival. The study by Block et al¹ highlights the importance of assessing the factors that enable health systems to adapt and innovate so that we can better understand hospital-level variation in outcomes.

Several studies have examined variation in outcomes of patients with COVID-19, with emphasis on hospital-level factors such as geographic location, workforce and resource availability, and COVID-19 community prevalence.^1,2 Block et al¹ examine variation in COVID-19 mortality across 117 US hospitals, exploring whether COVID-19 admission volume was associated with mortality. While their results suggest that patients admitted to hospitals in the highest quintiles of COVID-19 caseload had higher odds of in-hospital death, the authors were not able to fully adjust for severity of illness, tempering our ability to draw conclusions. However, their finding is consistent with work showing that emergency department crowding and high hospital utilization are associated with excess mortality.

Block et al¹ also found variation within quintiles of COVID-19 burden, suggesting that other hospital-level factors are influencing their performance. In response to the initial surge of COVID-19 in the United States, hospitals and healthcare systems made rapid, often major, adjustments to provide care. Four interdependent components contribute to an effective surge response: system, space, staff, and supplies. Although all four components are important, effective systems are critical. Systems domains include command, or the creation of leadership teams throughout the organization; control, or management, of infrastructure; communication of rapid, comprehensible messages internally and externally; coordination of resources across departments and professions; and continuity of operations.³ Little is known about how well hospitals have implemented these systems components throughout the pandemic, and while Janke et al² examined the association of resources with outcomes, neither their study nor Block et al’s was able to account for other organizational or systems-based aspects of surge response.

Studies that help us understand the organizational factors and care-delivery adaptations associated with better outcomes for patients with COVID-19 are sorely needed, and could provide important insights for organizational adaptation and change more generally. Janke et al² and, in their accompanying editorial, Auerbach and Greysen,⁴ call for “innovative protocols” and “flexibility” to meet the needs of high-demand, novel situations. However, organizations’ ability to innovate and adapt relies on their relationships and teamwork capability.

The relational infrastructure within an organization provides the basis for effective teamwork, facilitating other aspects of an organization’s surge response and ability to adapt. Relationships characterized by trust and mindfulness create a context of psychological safety that encourages sharing new ideas, and enable teams to rapidly make sense of new situations and create shared understandings that facilitate effective action: improvising, adapting, and learning. Trust and psychological safety are especially important during crises, as decision-making tends to evolve toward top-down processes in times of crisis.

Hospitals currently collect few data that speak to relationships and teamwork, limiting our ability to study these vital organizational characteristics and their role in the larger COVID-19 response. Surveys related to patient safety culture or provider wellness and burnout are likely the only data regularly collected by hospitals. Expanding these data to include measures of relational infrastructure will create more robust data not only to conduct research regarding organizational factors that are associated with patient outcomes, but also to allow health systems to improve relationships and teaming as a means of improving outcomes. Examples include relational coordination,⁵ relationships,⁶and learning scales.⁷

The hospitals to which patients are admitted make a difference in patient survival. The study by Block et al¹ highlights the importance of assessing the factors that enable health systems to adapt and innovate so that we can better understand hospital-level variation in outcomes.

Several studies have examined variation in outcomes of patients with COVID-19, with emphasis on hospital-level factors such as geographic location, workforce and resource availability, and COVID-19 community prevalence.^1,2 Block et al¹ examine variation in COVID-19 mortality across 117 US hospitals, exploring whether COVID-19 admission volume was associated with mortality. While their results suggest that patients admitted to hospitals in the highest quintiles of COVID-19 caseload had higher odds of in-hospital death, the authors were not able to fully adjust for severity of illness, tempering our ability to draw conclusions. However, their finding is consistent with work showing that emergency department crowding and high hospital utilization are associated with excess mortality.

Block et al¹ also found variation within quintiles of COVID-19 burden, suggesting that other hospital-level factors are influencing their performance. In response to the initial surge of COVID-19 in the United States, hospitals and healthcare systems made rapid, often major, adjustments to provide care. Four interdependent components contribute to an effective surge response: system, space, staff, and supplies. Although all four components are important, effective systems are critical. Systems domains include command, or the creation of leadership teams throughout the organization; control, or management, of infrastructure; communication of rapid, comprehensible messages internally and externally; coordination of resources across departments and professions; and continuity of operations.³ Little is known about how well hospitals have implemented these systems components throughout the pandemic, and while Janke et al² examined the association of resources with outcomes, neither their study nor Block et al’s was able to account for other organizational or systems-based aspects of surge response.

Studies that help us understand the organizational factors and care-delivery adaptations associated with better outcomes for patients with COVID-19 are sorely needed, and could provide important insights for organizational adaptation and change more generally. Janke et al² and, in their accompanying editorial, Auerbach and Greysen,⁴ call for “innovative protocols” and “flexibility” to meet the needs of high-demand, novel situations. However, organizations’ ability to innovate and adapt relies on their relationships and teamwork capability.

The relational infrastructure within an organization provides the basis for effective teamwork, facilitating other aspects of an organization’s surge response and ability to adapt. Relationships characterized by trust and mindfulness create a context of psychological safety that encourages sharing new ideas, and enable teams to rapidly make sense of new situations and create shared understandings that facilitate effective action: improvising, adapting, and learning. Trust and psychological safety are especially important during crises, as decision-making tends to evolve toward top-down processes in times of crisis.

Hospitals currently collect few data that speak to relationships and teamwork, limiting our ability to study these vital organizational characteristics and their role in the larger COVID-19 response. Surveys related to patient safety culture or provider wellness and burnout are likely the only data regularly collected by hospitals. Expanding these data to include measures of relational infrastructure will create more robust data not only to conduct research regarding organizational factors that are associated with patient outcomes, but also to allow health systems to improve relationships and teaming as a means of improving outcomes. Examples include relational coordination,⁵ relationships,⁶and learning scales.⁷

The hospitals to which patients are admitted make a difference in patient survival. The study by Block et al¹ highlights the importance of assessing the factors that enable health systems to adapt and innovate so that we can better understand hospital-level variation in outcomes.

Since the onset of the COVID-19 pandemic, the proclivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults and its relative sparing of pediatric populations has been well characterized. Accordingly, policymakers have devoted significant attention to SARS-CoV-2’s impact on adult hospitals. Less consideration, however, has been given to children’s hospitals, which responded to the pandemic by suspending noncritical care encounters, conserving personal protective equipment, and implementing alternative care models.¹ While important, these strategic decisions may threaten the financial health of children’s hospitals.

In this issue of the Journal of Hospital Medicine, Synhorst et al¹ describe the impact of COVID-19 on US children’s hospitals.The authors utilized the Children’s Hospital Association’s PROSPECT database to compare year-over-year trends in healthcare encounters and hospital charges before and during the COVID-19 pandemic at 26 tertiary hospitals. The analysis focused on the first wave of COVID-19 in the United States from February through June 2020.

The results are staggering. Compared with 2019, the authors found significant decreases in healthcare encounters for all children’s hospitals beginning in March 2020, with a nadir in mid-April (corresponding to the first peak in adult hospitalizations). Inpatient bed days, emergency department (ED) visits, and surgeries decreased by a median of 36%, 65%, and 77%, respectively, per hospital during the nadir. Charges from February 1 to June 30, 2020, decreased by a median 24% per children’s hospital as compared to 2019—corresponding to a median $276 million decrease in charges per hospital. A quarter of hospitals faced more than $400 million in lost charges.¹

Why do these trends matter? Large decreases in utilization and associated charges likely represent significant unmet demand for child healthcare for both acute and chronic disease management. For example, with limited in-person evaluation available at the onset of illness, caregivers are presenting to EDs with sicker children.² With a shift to virtual care, clinicians may miss signs of child abuse from violence in the home—which can escalate during isolation.³ Children with chronic conditions may also be left without surveillance mechanisms, which may partly explain the autumn 2020 surge in acute mental health-related ED presentations.⁴ Furthermore, telemedicine may exacerbate care inequities for vulnerable populations lacking resources and/or English proficiency.

There is also a larger policy perspective to consider in evaluating these data: Because children’s hospitals largely operate in a fee-for-service reimbursement model, they often rely on marginal revenues to support mission-driven programming. In other words, revenue streams from profitable care segments (eg, elective surgeries) often help sustain institutional platforms operating at a loss, such as community safety net programs. Consequently, threats to marginal revenues can place mission-driven programming in jeopardy of being reduced or terminated.

The Synhorst et al¹ study was limited to hospital charges, which likely overestimate revenue losses based on actual reimbursements. Yet, this is the first study to quantify COVID-19’s financial toll on children’s hospitals, and charges offer a reasonable proxy for balance sheet trends. Thus, it is safe to assume that most hospitals incurred substantial losses during the 2020 fiscal year. Unfortunately, as the authors highlight, these losses differentially impacted hospitals based on existing resources¹—so some hospitals were likely forced to cut programs or reduce staff in an effort to return to profitability. In this way, COVID-19 has exposed the fragility of the fee-for-service model that children’s hospitals rely on for both patients and staff.

Children’s hospitals and the services they provide are essential to the health and well-being of children. The critical losses sustained by children’s hospitals due to COVID-19 threaten their ability to promote child health in the near and long term, with the greatest risk to vulnerable populations. Policymakers must act now to preserve these essential services for children.

Since the onset of the COVID-19 pandemic, the proclivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults and its relative sparing of pediatric populations has been well characterized. Accordingly, policymakers have devoted significant attention to SARS-CoV-2’s impact on adult hospitals. Less consideration, however, has been given to children’s hospitals, which responded to the pandemic by suspending noncritical care encounters, conserving personal protective equipment, and implementing alternative care models.¹ While important, these strategic decisions may threaten the financial health of children’s hospitals.

In this issue of the Journal of Hospital Medicine, Synhorst et al¹ describe the impact of COVID-19 on US children’s hospitals.The authors utilized the Children’s Hospital Association’s PROSPECT database to compare year-over-year trends in healthcare encounters and hospital charges before and during the COVID-19 pandemic at 26 tertiary hospitals. The analysis focused on the first wave of COVID-19 in the United States from February through June 2020.

The results are staggering. Compared with 2019, the authors found significant decreases in healthcare encounters for all children’s hospitals beginning in March 2020, with a nadir in mid-April (corresponding to the first peak in adult hospitalizations). Inpatient bed days, emergency department (ED) visits, and surgeries decreased by a median of 36%, 65%, and 77%, respectively, per hospital during the nadir. Charges from February 1 to June 30, 2020, decreased by a median 24% per children’s hospital as compared to 2019—corresponding to a median $276 million decrease in charges per hospital. A quarter of hospitals faced more than $400 million in lost charges.¹

Why do these trends matter? Large decreases in utilization and associated charges likely represent significant unmet demand for child healthcare for both acute and chronic disease management. For example, with limited in-person evaluation available at the onset of illness, caregivers are presenting to EDs with sicker children.² With a shift to virtual care, clinicians may miss signs of child abuse from violence in the home—which can escalate during isolation.³ Children with chronic conditions may also be left without surveillance mechanisms, which may partly explain the autumn 2020 surge in acute mental health-related ED presentations.⁴ Furthermore, telemedicine may exacerbate care inequities for vulnerable populations lacking resources and/or English proficiency.

There is also a larger policy perspective to consider in evaluating these data: Because children’s hospitals largely operate in a fee-for-service reimbursement model, they often rely on marginal revenues to support mission-driven programming. In other words, revenue streams from profitable care segments (eg, elective surgeries) often help sustain institutional platforms operating at a loss, such as community safety net programs. Consequently, threats to marginal revenues can place mission-driven programming in jeopardy of being reduced or terminated.

The Synhorst et al¹ study was limited to hospital charges, which likely overestimate revenue losses based on actual reimbursements. Yet, this is the first study to quantify COVID-19’s financial toll on children’s hospitals, and charges offer a reasonable proxy for balance sheet trends. Thus, it is safe to assume that most hospitals incurred substantial losses during the 2020 fiscal year. Unfortunately, as the authors highlight, these losses differentially impacted hospitals based on existing resources¹—so some hospitals were likely forced to cut programs or reduce staff in an effort to return to profitability. In this way, COVID-19 has exposed the fragility of the fee-for-service model that children’s hospitals rely on for both patients and staff.

Children’s hospitals and the services they provide are essential to the health and well-being of children. The critical losses sustained by children’s hospitals due to COVID-19 threaten their ability to promote child health in the near and long term, with the greatest risk to vulnerable populations. Policymakers must act now to preserve these essential services for children.

Since the onset of the COVID-19 pandemic, the proclivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for adults and its relative sparing of pediatric populations has been well characterized. Accordingly, policymakers have devoted significant attention to SARS-CoV-2’s impact on adult hospitals. Less consideration, however, has been given to children’s hospitals, which responded to the pandemic by suspending noncritical care encounters, conserving personal protective equipment, and implementing alternative care models.¹ While important, these strategic decisions may threaten the financial health of children’s hospitals.

In this issue of the Journal of Hospital Medicine, Synhorst et al¹ describe the impact of COVID-19 on US children’s hospitals.The authors utilized the Children’s Hospital Association’s PROSPECT database to compare year-over-year trends in healthcare encounters and hospital charges before and during the COVID-19 pandemic at 26 tertiary hospitals. The analysis focused on the first wave of COVID-19 in the United States from February through June 2020.

The results are staggering. Compared with 2019, the authors found significant decreases in healthcare encounters for all children’s hospitals beginning in March 2020, with a nadir in mid-April (corresponding to the first peak in adult hospitalizations). Inpatient bed days, emergency department (ED) visits, and surgeries decreased by a median of 36%, 65%, and 77%, respectively, per hospital during the nadir. Charges from February 1 to June 30, 2020, decreased by a median 24% per children’s hospital as compared to 2019—corresponding to a median $276 million decrease in charges per hospital. A quarter of hospitals faced more than $400 million in lost charges.¹

Why do these trends matter? Large decreases in utilization and associated charges likely represent significant unmet demand for child healthcare for both acute and chronic disease management. For example, with limited in-person evaluation available at the onset of illness, caregivers are presenting to EDs with sicker children.² With a shift to virtual care, clinicians may miss signs of child abuse from violence in the home—which can escalate during isolation.³ Children with chronic conditions may also be left without surveillance mechanisms, which may partly explain the autumn 2020 surge in acute mental health-related ED presentations.⁴ Furthermore, telemedicine may exacerbate care inequities for vulnerable populations lacking resources and/or English proficiency.

There is also a larger policy perspective to consider in evaluating these data: Because children’s hospitals largely operate in a fee-for-service reimbursement model, they often rely on marginal revenues to support mission-driven programming. In other words, revenue streams from profitable care segments (eg, elective surgeries) often help sustain institutional platforms operating at a loss, such as community safety net programs. Consequently, threats to marginal revenues can place mission-driven programming in jeopardy of being reduced or terminated.

The Synhorst et al¹ study was limited to hospital charges, which likely overestimate revenue losses based on actual reimbursements. Yet, this is the first study to quantify COVID-19’s financial toll on children’s hospitals, and charges offer a reasonable proxy for balance sheet trends. Thus, it is safe to assume that most hospitals incurred substantial losses during the 2020 fiscal year. Unfortunately, as the authors highlight, these losses differentially impacted hospitals based on existing resources¹—so some hospitals were likely forced to cut programs or reduce staff in an effort to return to profitability. In this way, COVID-19 has exposed the fragility of the fee-for-service model that children’s hospitals rely on for both patients and staff.

Children’s hospitals and the services they provide are essential to the health and well-being of children. The critical losses sustained by children’s hospitals due to COVID-19 threaten their ability to promote child health in the near and long term, with the greatest risk to vulnerable populations. Policymakers must act now to preserve these essential services for children.

Approximately 68 million cases of sexually transmitted infections are reported in the United States each year, yet antiquated approaches to STI prevention, in addition to health care inequities and lack of funding, have substantially prevented providers and officials from curbing the spread. In response to rising case numbers, the National Academies of Sciences, Engineering, and Medicine released a report this week with recommendations to modernize the nation’s STI surveillance and monitoring systems, increase the capabilities of the STI workforce, and address structural barriers to STI prevention and access to care.

Given the rising rates of STIs and the urgent, unmet need for prevention and treatment, the Centers for Disease Control and Prevention’s National Association of County and City Health Officials commissioned the National Academies to develop actionable recommendations to control STIs. The new report marks a long road toward the public’s willingness to discuss STDs, or what a 1997 Institute of Medicine report described as a “hidden epidemic” that had been largely neglected in public discourse.

Jeffrey Crowley, MPH, committee member and an author of the new National Academies report, said in an interview that, despite the increased openness to discuss STIs in today’s society, STD rates since the late 1990s have gotten much worse. Lack of appropriate governmental funding for research and drug development, structural inequities, and persisting stigmatization are key drivers for rising rates, explained Mr. Crowley.
 

Addressing structural barriers to STI prevention

Playing a prominent role in the National Academies report are issues of structural and institutional barriers to STI prevention and care. In the report, the authors argued that a policy-based approach should seek to promote sexual health and eliminate structural racism and inequities to drive improvements in STI management.

“We think it’s these structural factors that are central to all the inequities that play out,” said Mr. Crowley, “and they either don’t get any attention or, if they do get attention, people don’t really speak concretely enough about how we address them.”

The concrete steps, as outlined in the report, begin with addressing factors that involve the health care industry at large. Automatic STI screening as part of routine visits, alerts in electronic health records that remind clinicians to screen patients, and reminders to test patients can be initial low-cost actions health care systems can take to improve STI testing, particularly in marginalized communities. Mr. Crowley noted that greater evidence is needed to support further steps to address structural factors that contribute to barriers in STI screening and treatment access.

Given the complexities inherent in structural barriers to STI care, the report calls on a whole-government response, in partnership with affected communities, to normalize discussions involving sexual well-being. “We have to ask ourselves how we can build healthier communities and how can we integrate sexual health into that dialogue in a way that improves our response to STI prevention and control,” Mr. Crowley explained.
 

Harnessing AI and dating apps

The report also addresses the power of artificial intelligence to predict STI rates and to discover trends in risk factors, both of which may improve STI surveillance and assist in the development of tailored interventions. The report calls for policy that will enable companies and the government to capitalize on AI to evaluate large collections of data in EHRs, insurance claims databases, social media, search engines, and even dating apps.

In particular, dating apps could be an avenue through which the public and private sectors could improve STI prevention, diagnosis, and treatment. “People want to focus on this idea of whether these apps increase transmission risk,” said Mr. Crowley. “But we would say that this is asking the wrong question, because these technologies are not going away.” He noted that private and public enterprises could work together to leverage these technologies to increase awareness of prevention and testing.
 

Unifying the STI/HIV and COVID-19 workforce

The report also recommends that the nation unify the STI/HIV workforce with the COVID-19 workforce. Given the high levels of expertise in these professional working groups, the report suggests unification could potentially address both the current crisis and possible future disease outbreaks. Combining COVID-19 response teams with underresourced STI/HIV programs may also improve the delivery of STI testing, considering that STI testing programs have had to compete for resources during the pandemic.

Addressing stigma

The National Academies report also addresses the ongoing issue of stigma, which results from “blaming” individuals and the choices they make so as to create shame, embarrassment, and discrimination. Because of stigma, sexually active people may be unwilling to seek recommended screening, which can lead to delays in diagnosis and treatment and can increase the risk for negative health outcomes.

“As a nation, we’ve almost focused too intently on individual-level factors in a way that’s driven stigma and really hasn’t been helpful for combating the problem,” said Mr. Crowley. He added that, instead of focusing solely on individual-level choices, the nation should instead work to reframe sexual health as a key aspect of overall physical, mental, and emotional well-being. Doing so could create more opportunities to address structural barriers to STI prevention and ensure that more prevention and screening services are available in stigma-free environments.

“I know what we’re recommending is ambitious, but it’s not too big to be achieved, and we’re not saying tomorrow we’re going to transform the world,” Mr. Crowley concluded. “It’s a puzzle with many pieces, but the long-term impact is really all of these pieces fitting together so that, over time, we can reduce the burden STIs have on the population.”
 

Implications for real-world change

H. Hunter Handsfield, MD, professor emeritus of medicine for the Center for AIDS and STD at the University of Washington, Seattle, said in an interview that this report essentially is a response to evolving societal changes, new and emerging means of social engagement, and increased focus on racial/ethnic disparities. “These features have all come to the forefront of health care and general policy discussions in recent years,” said Dr. Handsfield, who was not part of the committee that developed the NAS report.

Greater scrutiny on public health infrastructure and its relationship with health disparities in the United States makes the publication of these new recommendations especially appropriate during this era of enhanced focus on social justice. Although the report features the tone and quality needed to bolster bipartisan support, said Dr. Handsfield, it’s hard to predict whether such support will come to fruition in today’s political environment.

In terms of the effects the recommendations may have on STI rates, Dr. Handsfield noted that cherry-picking elements from the report to direct policy may result in its having only a trivial impact. “The report is really an appropriate and necessary response, and almost all the recommendations made can be helpful,” he said, “but for true effectiveness, all the elements need to be implemented to drive policy and funding.”

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

Approximately 68 million cases of sexually transmitted infections are reported in the United States each year, yet antiquated approaches to STI prevention, in addition to health care inequities and lack of funding, have substantially prevented providers and officials from curbing the spread. In response to rising case numbers, the National Academies of Sciences, Engineering, and Medicine released a report this week with recommendations to modernize the nation’s STI surveillance and monitoring systems, increase the capabilities of the STI workforce, and address structural barriers to STI prevention and access to care.

Given the rising rates of STIs and the urgent, unmet need for prevention and treatment, the Centers for Disease Control and Prevention’s National Association of County and City Health Officials commissioned the National Academies to develop actionable recommendations to control STIs. The new report marks a long road toward the public’s willingness to discuss STDs, or what a 1997 Institute of Medicine report described as a “hidden epidemic” that had been largely neglected in public discourse.

Jeffrey Crowley, MPH, committee member and an author of the new National Academies report, said in an interview that, despite the increased openness to discuss STIs in today’s society, STD rates since the late 1990s have gotten much worse. Lack of appropriate governmental funding for research and drug development, structural inequities, and persisting stigmatization are key drivers for rising rates, explained Mr. Crowley.
 

Addressing structural barriers to STI prevention

Playing a prominent role in the National Academies report are issues of structural and institutional barriers to STI prevention and care. In the report, the authors argued that a policy-based approach should seek to promote sexual health and eliminate structural racism and inequities to drive improvements in STI management.

“We think it’s these structural factors that are central to all the inequities that play out,” said Mr. Crowley, “and they either don’t get any attention or, if they do get attention, people don’t really speak concretely enough about how we address them.”

The concrete steps, as outlined in the report, begin with addressing factors that involve the health care industry at large. Automatic STI screening as part of routine visits, alerts in electronic health records that remind clinicians to screen patients, and reminders to test patients can be initial low-cost actions health care systems can take to improve STI testing, particularly in marginalized communities. Mr. Crowley noted that greater evidence is needed to support further steps to address structural factors that contribute to barriers in STI screening and treatment access.

Given the complexities inherent in structural barriers to STI care, the report calls on a whole-government response, in partnership with affected communities, to normalize discussions involving sexual well-being. “We have to ask ourselves how we can build healthier communities and how can we integrate sexual health into that dialogue in a way that improves our response to STI prevention and control,” Mr. Crowley explained.
 

Harnessing AI and dating apps

The report also addresses the power of artificial intelligence to predict STI rates and to discover trends in risk factors, both of which may improve STI surveillance and assist in the development of tailored interventions. The report calls for policy that will enable companies and the government to capitalize on AI to evaluate large collections of data in EHRs, insurance claims databases, social media, search engines, and even dating apps.

In particular, dating apps could be an avenue through which the public and private sectors could improve STI prevention, diagnosis, and treatment. “People want to focus on this idea of whether these apps increase transmission risk,” said Mr. Crowley. “But we would say that this is asking the wrong question, because these technologies are not going away.” He noted that private and public enterprises could work together to leverage these technologies to increase awareness of prevention and testing.
 

Unifying the STI/HIV and COVID-19 workforce

The report also recommends that the nation unify the STI/HIV workforce with the COVID-19 workforce. Given the high levels of expertise in these professional working groups, the report suggests unification could potentially address both the current crisis and possible future disease outbreaks. Combining COVID-19 response teams with underresourced STI/HIV programs may also improve the delivery of STI testing, considering that STI testing programs have had to compete for resources during the pandemic.

Addressing stigma

The National Academies report also addresses the ongoing issue of stigma, which results from “blaming” individuals and the choices they make so as to create shame, embarrassment, and discrimination. Because of stigma, sexually active people may be unwilling to seek recommended screening, which can lead to delays in diagnosis and treatment and can increase the risk for negative health outcomes.

“As a nation, we’ve almost focused too intently on individual-level factors in a way that’s driven stigma and really hasn’t been helpful for combating the problem,” said Mr. Crowley. He added that, instead of focusing solely on individual-level choices, the nation should instead work to reframe sexual health as a key aspect of overall physical, mental, and emotional well-being. Doing so could create more opportunities to address structural barriers to STI prevention and ensure that more prevention and screening services are available in stigma-free environments.

“I know what we’re recommending is ambitious, but it’s not too big to be achieved, and we’re not saying tomorrow we’re going to transform the world,” Mr. Crowley concluded. “It’s a puzzle with many pieces, but the long-term impact is really all of these pieces fitting together so that, over time, we can reduce the burden STIs have on the population.”
 

Implications for real-world change

H. Hunter Handsfield, MD, professor emeritus of medicine for the Center for AIDS and STD at the University of Washington, Seattle, said in an interview that this report essentially is a response to evolving societal changes, new and emerging means of social engagement, and increased focus on racial/ethnic disparities. “These features have all come to the forefront of health care and general policy discussions in recent years,” said Dr. Handsfield, who was not part of the committee that developed the NAS report.

Greater scrutiny on public health infrastructure and its relationship with health disparities in the United States makes the publication of these new recommendations especially appropriate during this era of enhanced focus on social justice. Although the report features the tone and quality needed to bolster bipartisan support, said Dr. Handsfield, it’s hard to predict whether such support will come to fruition in today’s political environment.

In terms of the effects the recommendations may have on STI rates, Dr. Handsfield noted that cherry-picking elements from the report to direct policy may result in its having only a trivial impact. “The report is really an appropriate and necessary response, and almost all the recommendations made can be helpful,” he said, “but for true effectiveness, all the elements need to be implemented to drive policy and funding.”

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

Approximately 68 million cases of sexually transmitted infections are reported in the United States each year, yet antiquated approaches to STI prevention, in addition to health care inequities and lack of funding, have substantially prevented providers and officials from curbing the spread. In response to rising case numbers, the National Academies of Sciences, Engineering, and Medicine released a report this week with recommendations to modernize the nation’s STI surveillance and monitoring systems, increase the capabilities of the STI workforce, and address structural barriers to STI prevention and access to care.

Given the rising rates of STIs and the urgent, unmet need for prevention and treatment, the Centers for Disease Control and Prevention’s National Association of County and City Health Officials commissioned the National Academies to develop actionable recommendations to control STIs. The new report marks a long road toward the public’s willingness to discuss STDs, or what a 1997 Institute of Medicine report described as a “hidden epidemic” that had been largely neglected in public discourse.

Jeffrey Crowley, MPH, committee member and an author of the new National Academies report, said in an interview that, despite the increased openness to discuss STIs in today’s society, STD rates since the late 1990s have gotten much worse. Lack of appropriate governmental funding for research and drug development, structural inequities, and persisting stigmatization are key drivers for rising rates, explained Mr. Crowley.
 

Addressing structural barriers to STI prevention

Playing a prominent role in the National Academies report are issues of structural and institutional barriers to STI prevention and care. In the report, the authors argued that a policy-based approach should seek to promote sexual health and eliminate structural racism and inequities to drive improvements in STI management.

“We think it’s these structural factors that are central to all the inequities that play out,” said Mr. Crowley, “and they either don’t get any attention or, if they do get attention, people don’t really speak concretely enough about how we address them.”

The concrete steps, as outlined in the report, begin with addressing factors that involve the health care industry at large. Automatic STI screening as part of routine visits, alerts in electronic health records that remind clinicians to screen patients, and reminders to test patients can be initial low-cost actions health care systems can take to improve STI testing, particularly in marginalized communities. Mr. Crowley noted that greater evidence is needed to support further steps to address structural factors that contribute to barriers in STI screening and treatment access.

Given the complexities inherent in structural barriers to STI care, the report calls on a whole-government response, in partnership with affected communities, to normalize discussions involving sexual well-being. “We have to ask ourselves how we can build healthier communities and how can we integrate sexual health into that dialogue in a way that improves our response to STI prevention and control,” Mr. Crowley explained.
 

Harnessing AI and dating apps

The report also addresses the power of artificial intelligence to predict STI rates and to discover trends in risk factors, both of which may improve STI surveillance and assist in the development of tailored interventions. The report calls for policy that will enable companies and the government to capitalize on AI to evaluate large collections of data in EHRs, insurance claims databases, social media, search engines, and even dating apps.

In particular, dating apps could be an avenue through which the public and private sectors could improve STI prevention, diagnosis, and treatment. “People want to focus on this idea of whether these apps increase transmission risk,” said Mr. Crowley. “But we would say that this is asking the wrong question, because these technologies are not going away.” He noted that private and public enterprises could work together to leverage these technologies to increase awareness of prevention and testing.
 

Unifying the STI/HIV and COVID-19 workforce

The report also recommends that the nation unify the STI/HIV workforce with the COVID-19 workforce. Given the high levels of expertise in these professional working groups, the report suggests unification could potentially address both the current crisis and possible future disease outbreaks. Combining COVID-19 response teams with underresourced STI/HIV programs may also improve the delivery of STI testing, considering that STI testing programs have had to compete for resources during the pandemic.

Addressing stigma

The National Academies report also addresses the ongoing issue of stigma, which results from “blaming” individuals and the choices they make so as to create shame, embarrassment, and discrimination. Because of stigma, sexually active people may be unwilling to seek recommended screening, which can lead to delays in diagnosis and treatment and can increase the risk for negative health outcomes.

“As a nation, we’ve almost focused too intently on individual-level factors in a way that’s driven stigma and really hasn’t been helpful for combating the problem,” said Mr. Crowley. He added that, instead of focusing solely on individual-level choices, the nation should instead work to reframe sexual health as a key aspect of overall physical, mental, and emotional well-being. Doing so could create more opportunities to address structural barriers to STI prevention and ensure that more prevention and screening services are available in stigma-free environments.

“I know what we’re recommending is ambitious, but it’s not too big to be achieved, and we’re not saying tomorrow we’re going to transform the world,” Mr. Crowley concluded. “It’s a puzzle with many pieces, but the long-term impact is really all of these pieces fitting together so that, over time, we can reduce the burden STIs have on the population.”
 

Implications for real-world change

H. Hunter Handsfield, MD, professor emeritus of medicine for the Center for AIDS and STD at the University of Washington, Seattle, said in an interview that this report essentially is a response to evolving societal changes, new and emerging means of social engagement, and increased focus on racial/ethnic disparities. “These features have all come to the forefront of health care and general policy discussions in recent years,” said Dr. Handsfield, who was not part of the committee that developed the NAS report.

Greater scrutiny on public health infrastructure and its relationship with health disparities in the United States makes the publication of these new recommendations especially appropriate during this era of enhanced focus on social justice. Although the report features the tone and quality needed to bolster bipartisan support, said Dr. Handsfield, it’s hard to predict whether such support will come to fruition in today’s political environment.

In terms of the effects the recommendations may have on STI rates, Dr. Handsfield noted that cherry-picking elements from the report to direct policy may result in its having only a trivial impact. “The report is really an appropriate and necessary response, and almost all the recommendations made can be helpful,” he said, “but for true effectiveness, all the elements need to be implemented to drive policy and funding.”

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

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

Two reports support the safety and immunogenicity of SARS-CoV-2 mRNA vaccines in patients with rheumatic and musculoskeletal diseases (RMDs) and represent the first available data on such patients.

peterschreiber_media/iStock/Getty Images

In an observational cohort study published in Annals of the Rheumatic Diseases, Caoilfhionn M. Connolly, MD, of Johns Hopkins University, Baltimore, and colleagues reviewed data from 325 adults with RMDs who received the first dose of SARS-CoV-2 mRNA vaccine during the period of Dec. 17, 2020, to Feb. 11, 2021. Of these, 51% received the Pfizer/BioNTech vaccine and 49% received the Moderna vaccine.

The patients, who were invited to participate on social media, were aged 34-54 years, 96% were women, and 89% were White. Inflammatory arthritis was the most common RMD condition (38%), followed by systemic lupus erythematosus (28%) and overlap connective tissue disease (19%). The patients were using a range of immunomodulatory treatment regimens, including nonbiologic disease modifying antirheumatic drugs (DMARDs) in 44%, biologics in 19%, and combination therapy in 37%.

Overall, 89% of patients reported localized symptoms of pain, swelling, and erythema, and 69% reported systemic symptoms. Fatigue was the most common systemic symptom, and 7.4% reported severe fatigue.

None of the patients experienced allergic reactions requiring epinephrine, and 3% reported new infections that required treatment.

“These early, reassuring results may ameliorate concern among patients and provide guidance for rheumatology providers in critical discussions regarding vaccine hesitancy or refusal,” they concluded.

Antibody responses

In another study published in Annals of the Rheumatic Diseases by the same group of researchers, antibody responses against the receptor binding domain of the SARS-CoV-2 spike protein were seen in 74% of 123 adults with an RMD at 18-26 days after receiving a first dose of SARS-CoV-2 mRNA vaccine (52% Pfizer vaccine and 48% Moderna) between Jan. 8, 2021, and Feb. 12, 2021.

The most common diagnoses in these patients were inflammatory arthritis (28%), systemic lupus erythematosus (20%), and Sjögren’s syndrome (13%). A total of 28% of participants reported taking no immunomodulatory agents, 19% reported nonbiologic DMARDs, 14% reported biologic DMARDs, and 19% reported combination therapy.

Although no differences appeared based on disease groups or overall categories of immunomodulatory therapies, patients whose treatment included mycophenolate or rituximab were significantly less likely to develop antibody responses than were patients not taking these medications (P = .001 and P = .04, respectively). Although rituximab and methotrexate have been associated with reduced responses to vaccines such as the flu vaccine, methotrexate was not associated with reduced vaccine response in this study. A total of 94% of patients taking a tumor necrosis factor inhibitor had detectable antibodies.

The studies’ findings were limited by several factors including a lack of longer-term safety data; the small, nonrandomized sample of mainly white women; limited information on immunomodulatory drug dosage and timing; lack of serial antibody measurements; use of an enzyme immunoassay designed to detect antibody response after natural infection; and the inclusion of data only on the first dose of a two-dose vaccine series, the researchers noted. However, the data should provide additional reassurance to RMD patients and their health care teams about vaccination against COVID-19, they said.

Both studies were supported by the Ben-Dov family. In addition, the studies were supported by grants to various study authors from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the Transplantation and Immunology Research Network of the American Society of Transplantation. One author disclosed financial relationships with Sanofi, Novartis, CSL Behring, Jazz Pharmaceuticals, Veloxis, Mallinckrodt, and Thermo Fisher Scientific. The other researchers had no financial conflicts to disclose.

The medical community may have paused during the COVID-19 pandemic, but commercial payers kept pushing forward with new coverage restrictions, expanding the number of services and procedures requiring prior authorization (PA) and restricting covered drugs. As 2020 closed and with 2021 barely underway, the American Gastroenterological Association has been holding discussions with major payers to stop implementation of policies restricting gastroenterologists’ ability to prescribe the most appropriate drugs for their patients’ clinical situations.

The Government Affairs Committee’s Coverage and Reimbursement Subcommittee (CRS) works with commercial payers on issues affecting gastroenterologists and identifies outside experts on the policy subject when necessary. The subcommittee recently worked with UnitedHealthcare on a coverage policy change to make Inflictra (infliximab-dyyb) and Avsola (infliximab-axxq) its preferred products and move Remicade (infliximab) and Renflexis (infliximab-abda) to its nonpreferred list, as announced in UnitedHealthcare’s Medical benefit specialty drug update bulletin. The CRS identified Sundeep Singh, MD, an inflammatory bowel disease specialist from Stanford (Calif.) University, to engage in discussion with UnitedHealthcare on behalf of AGA and lead a multisociety effort with the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition; the American Society for Gastrointestinal Endoscopy; and the American College of Gastroenterology.

After conversations with our physician experts, UnitedHealthcare agreed to notify its medical directors to allow pediatric patients 16 years and younger and currently on a nonpreferred product, such as Remicade, to remain on it if that is the recommendation of the treating physician. Adult patients meeting the following conditions may be allowed to remain on nonpreferred products, but will require the prescribing provider to request a review and a determination will be made on a case-by-case basis:

• Adult patients currently on induction of Remicade for less than 18 months will not be required to switch.
• Adult patients who are having a flare of active disease, who are, therefore, not stable, will not be required to switch.

AGA experts are a vital part of CRS’s work with commercial payers. Dr. Singh and his fellow IBD experts who participated in discussion with UnitedHealthcare helped the payer understand why its original policy implementing nonmedical switching without exceptions was harmful to patients. Dr. Singh had this to say about his experience with the process:

“Thanks to the coordinated efforts between AGA, NASPGHAN, ACG, ASGE, and UnitedHealthcare, we were able to reconcile the policy and knowledge gaps to protect our patients with inflammatory bowel disease. While there are significant cost savings associated with biosimilar use, we wanted to temper the health plan’s initial enthusiasm with the potential costs in patients whose clinical and economic outcomes are not certain yet. As we anticipate other health plans will implement similar policies, this effort may provide a road map for the future.”

The CRS also works with pharmacy benefit management organizations. The AGA joined the ASGE and ACG to ask Express Scripts to not exclude coverage of brand colonoscopy preparations such as Suprep, Clenpiq, and Plenvu. The formulary currently plans to cover only generic products for colon cleansing beginning April 1, 2021, primarily 4-liter polyethylene glycol electrolyte solutions (PEG-ELS).

Clinical representatives and staff from AGA, ACG, and ASGE participated in a fruitful discussion with the leadership of Express Scripts and presented several key discussion points in favor of keeping coverage of brand colonoscopy bowel preparations in addition to PEG-ELS. The multisociety group presented views from practicing gastroenterologists as well as from academicians about the safety and benefits of low-volume preparations for a quality screening colonoscopic exam especially in certain patient populations. Limiting choices of bowel preparations will deter patients from undergoing screening colonoscopies, which have been proven to prevent colorectal cancers. After the multisociety group pointed out the need to individualize the choice of bowel preparation to ensure safety and tolerability, Express Scripts will hopefully agree with the significance of having options for our patients. It was clear that the importance of patient preference and clinical appropriateness for different bowel preparation options was heard by the Express Scripts representatives, so we await their decision with hope.

The AGA is working to address issues with commercial payers, but to be effective we need to hear your experiences. We know commercial payers continue to develop increasingly restrictive PA policies and coverage conditions for procedures and drugs. Reach out to the AGA via the AGA Community, Twitter, or via email to Leslie Narramore, the director of regulatory affairs at AGA, at [email protected] to let us know what’s happening.

Seven options to consider if your PA has been rejected or claim has been denied

• Ask for the credentials of the payer representative who initially denied the request. Even when payer representatives are physicians, they are often not gastroenterologists. Ask to speak with a representative actively practicing gastroenterology.
• Ask to record your conversation with the payer representative for documentation purposes.
• Ask to speak directly to the payer’s medical director.
• Bring the complaint to the payer’s attention on social media. Using social media to bring attention to a denial can sometimes elicit quick, personal outreach from the payer to address the issue.
• Let the AGA know what’s happening. Reach out to the AGA via the AGA Community, via Twitter, or by emailing Leslie Narramore, the director of regulatory affairs at AGA ([email protected]).
• File a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to ensure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories. Find out your state’s complaint process because many state insurance commissioners have on online complaint forms. Keep records of all interactions with the insurance company to document that you have attempted to resolve the matter with the payer first.
• File a complaint at the federal level for states without an external review process. If your state doesn’t have an external review process that meets the minimum consumer protection standards, the federal government’s Department of Health & Human Services oversees an external review process for health insurance companies in your state. See www.healthcare.gov/appeal-insurance-company-decision/external-review/ for more information. In states where the federal government oversees the process, insurance companies may choose to participate in an HHS-administered process or contract with independent review organizations. If your plan doesn’t participate in a state or HHS-Administered Federal External Review Process, your health plan must contract with an independent review organization.

Dr. Guha is with the University of Texas Health Science Center in Houston. Dr. Upchurch is with Adena Health System in Chillicothe, Ohio. Both are AGA Coverage and Reimbursement Subcommittee members. The authors have no conflicts to declare.

The medical community may have paused during the COVID-19 pandemic, but commercial payers kept pushing forward with new coverage restrictions, expanding the number of services and procedures requiring prior authorization (PA) and restricting covered drugs. As 2020 closed and with 2021 barely underway, the American Gastroenterological Association has been holding discussions with major payers to stop implementation of policies restricting gastroenterologists’ ability to prescribe the most appropriate drugs for their patients’ clinical situations.

The Government Affairs Committee’s Coverage and Reimbursement Subcommittee (CRS) works with commercial payers on issues affecting gastroenterologists and identifies outside experts on the policy subject when necessary. The subcommittee recently worked with UnitedHealthcare on a coverage policy change to make Inflictra (infliximab-dyyb) and Avsola (infliximab-axxq) its preferred products and move Remicade (infliximab) and Renflexis (infliximab-abda) to its nonpreferred list, as announced in UnitedHealthcare’s Medical benefit specialty drug update bulletin. The CRS identified Sundeep Singh, MD, an inflammatory bowel disease specialist from Stanford (Calif.) University, to engage in discussion with UnitedHealthcare on behalf of AGA and lead a multisociety effort with the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition; the American Society for Gastrointestinal Endoscopy; and the American College of Gastroenterology.

After conversations with our physician experts, UnitedHealthcare agreed to notify its medical directors to allow pediatric patients 16 years and younger and currently on a nonpreferred product, such as Remicade, to remain on it if that is the recommendation of the treating physician. Adult patients meeting the following conditions may be allowed to remain on nonpreferred products, but will require the prescribing provider to request a review and a determination will be made on a case-by-case basis:

• Adult patients currently on induction of Remicade for less than 18 months will not be required to switch.
• Adult patients who are having a flare of active disease, who are, therefore, not stable, will not be required to switch.

AGA experts are a vital part of CRS’s work with commercial payers. Dr. Singh and his fellow IBD experts who participated in discussion with UnitedHealthcare helped the payer understand why its original policy implementing nonmedical switching without exceptions was harmful to patients. Dr. Singh had this to say about his experience with the process:

“Thanks to the coordinated efforts between AGA, NASPGHAN, ACG, ASGE, and UnitedHealthcare, we were able to reconcile the policy and knowledge gaps to protect our patients with inflammatory bowel disease. While there are significant cost savings associated with biosimilar use, we wanted to temper the health plan’s initial enthusiasm with the potential costs in patients whose clinical and economic outcomes are not certain yet. As we anticipate other health plans will implement similar policies, this effort may provide a road map for the future.”

The CRS also works with pharmacy benefit management organizations. The AGA joined the ASGE and ACG to ask Express Scripts to not exclude coverage of brand colonoscopy preparations such as Suprep, Clenpiq, and Plenvu. The formulary currently plans to cover only generic products for colon cleansing beginning April 1, 2021, primarily 4-liter polyethylene glycol electrolyte solutions (PEG-ELS).

Clinical representatives and staff from AGA, ACG, and ASGE participated in a fruitful discussion with the leadership of Express Scripts and presented several key discussion points in favor of keeping coverage of brand colonoscopy bowel preparations in addition to PEG-ELS. The multisociety group presented views from practicing gastroenterologists as well as from academicians about the safety and benefits of low-volume preparations for a quality screening colonoscopic exam especially in certain patient populations. Limiting choices of bowel preparations will deter patients from undergoing screening colonoscopies, which have been proven to prevent colorectal cancers. After the multisociety group pointed out the need to individualize the choice of bowel preparation to ensure safety and tolerability, Express Scripts will hopefully agree with the significance of having options for our patients. It was clear that the importance of patient preference and clinical appropriateness for different bowel preparation options was heard by the Express Scripts representatives, so we await their decision with hope.

The AGA is working to address issues with commercial payers, but to be effective we need to hear your experiences. We know commercial payers continue to develop increasingly restrictive PA policies and coverage conditions for procedures and drugs. Reach out to the AGA via the AGA Community, Twitter, or via email to Leslie Narramore, the director of regulatory affairs at AGA, at [email protected] to let us know what’s happening.

Seven options to consider if your PA has been rejected or claim has been denied

• Ask for the credentials of the payer representative who initially denied the request. Even when payer representatives are physicians, they are often not gastroenterologists. Ask to speak with a representative actively practicing gastroenterology.
• Ask to record your conversation with the payer representative for documentation purposes.
• Ask to speak directly to the payer’s medical director.
• Bring the complaint to the payer’s attention on social media. Using social media to bring attention to a denial can sometimes elicit quick, personal outreach from the payer to address the issue.
• Let the AGA know what’s happening. Reach out to the AGA via the AGA Community, via Twitter, or by emailing Leslie Narramore, the director of regulatory affairs at AGA ([email protected]).
• File a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to ensure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories. Find out your state’s complaint process because many state insurance commissioners have on online complaint forms. Keep records of all interactions with the insurance company to document that you have attempted to resolve the matter with the payer first.
• File a complaint at the federal level for states without an external review process. If your state doesn’t have an external review process that meets the minimum consumer protection standards, the federal government’s Department of Health & Human Services oversees an external review process for health insurance companies in your state. See www.healthcare.gov/appeal-insurance-company-decision/external-review/ for more information. In states where the federal government oversees the process, insurance companies may choose to participate in an HHS-administered process or contract with independent review organizations. If your plan doesn’t participate in a state or HHS-Administered Federal External Review Process, your health plan must contract with an independent review organization.

Dr. Guha is with the University of Texas Health Science Center in Houston. Dr. Upchurch is with Adena Health System in Chillicothe, Ohio. Both are AGA Coverage and Reimbursement Subcommittee members. The authors have no conflicts to declare.

The medical community may have paused during the COVID-19 pandemic, but commercial payers kept pushing forward with new coverage restrictions, expanding the number of services and procedures requiring prior authorization (PA) and restricting covered drugs. As 2020 closed and with 2021 barely underway, the American Gastroenterological Association has been holding discussions with major payers to stop implementation of policies restricting gastroenterologists’ ability to prescribe the most appropriate drugs for their patients’ clinical situations.

The Government Affairs Committee’s Coverage and Reimbursement Subcommittee (CRS) works with commercial payers on issues affecting gastroenterologists and identifies outside experts on the policy subject when necessary. The subcommittee recently worked with UnitedHealthcare on a coverage policy change to make Inflictra (infliximab-dyyb) and Avsola (infliximab-axxq) its preferred products and move Remicade (infliximab) and Renflexis (infliximab-abda) to its nonpreferred list, as announced in UnitedHealthcare’s Medical benefit specialty drug update bulletin. The CRS identified Sundeep Singh, MD, an inflammatory bowel disease specialist from Stanford (Calif.) University, to engage in discussion with UnitedHealthcare on behalf of AGA and lead a multisociety effort with the North American Society For Pediatric Gastroenterology, Hepatology & Nutrition; the American Society for Gastrointestinal Endoscopy; and the American College of Gastroenterology.

After conversations with our physician experts, UnitedHealthcare agreed to notify its medical directors to allow pediatric patients 16 years and younger and currently on a nonpreferred product, such as Remicade, to remain on it if that is the recommendation of the treating physician. Adult patients meeting the following conditions may be allowed to remain on nonpreferred products, but will require the prescribing provider to request a review and a determination will be made on a case-by-case basis:

• Adult patients currently on induction of Remicade for less than 18 months will not be required to switch.
• Adult patients who are having a flare of active disease, who are, therefore, not stable, will not be required to switch.

AGA experts are a vital part of CRS’s work with commercial payers. Dr. Singh and his fellow IBD experts who participated in discussion with UnitedHealthcare helped the payer understand why its original policy implementing nonmedical switching without exceptions was harmful to patients. Dr. Singh had this to say about his experience with the process:

“Thanks to the coordinated efforts between AGA, NASPGHAN, ACG, ASGE, and UnitedHealthcare, we were able to reconcile the policy and knowledge gaps to protect our patients with inflammatory bowel disease. While there are significant cost savings associated with biosimilar use, we wanted to temper the health plan’s initial enthusiasm with the potential costs in patients whose clinical and economic outcomes are not certain yet. As we anticipate other health plans will implement similar policies, this effort may provide a road map for the future.”

The CRS also works with pharmacy benefit management organizations. The AGA joined the ASGE and ACG to ask Express Scripts to not exclude coverage of brand colonoscopy preparations such as Suprep, Clenpiq, and Plenvu. The formulary currently plans to cover only generic products for colon cleansing beginning April 1, 2021, primarily 4-liter polyethylene glycol electrolyte solutions (PEG-ELS).

Clinical representatives and staff from AGA, ACG, and ASGE participated in a fruitful discussion with the leadership of Express Scripts and presented several key discussion points in favor of keeping coverage of brand colonoscopy bowel preparations in addition to PEG-ELS. The multisociety group presented views from practicing gastroenterologists as well as from academicians about the safety and benefits of low-volume preparations for a quality screening colonoscopic exam especially in certain patient populations. Limiting choices of bowel preparations will deter patients from undergoing screening colonoscopies, which have been proven to prevent colorectal cancers. After the multisociety group pointed out the need to individualize the choice of bowel preparation to ensure safety and tolerability, Express Scripts will hopefully agree with the significance of having options for our patients. It was clear that the importance of patient preference and clinical appropriateness for different bowel preparation options was heard by the Express Scripts representatives, so we await their decision with hope.

The AGA is working to address issues with commercial payers, but to be effective we need to hear your experiences. We know commercial payers continue to develop increasingly restrictive PA policies and coverage conditions for procedures and drugs. Reach out to the AGA via the AGA Community, Twitter, or via email to Leslie Narramore, the director of regulatory affairs at AGA, at [email protected] to let us know what’s happening.

Seven options to consider if your PA has been rejected or claim has been denied

• Ask for the credentials of the payer representative who initially denied the request. Even when payer representatives are physicians, they are often not gastroenterologists. Ask to speak with a representative actively practicing gastroenterology.
• Ask to record your conversation with the payer representative for documentation purposes.
• Ask to speak directly to the payer’s medical director.
• Bring the complaint to the payer’s attention on social media. Using social media to bring attention to a denial can sometimes elicit quick, personal outreach from the payer to address the issue.
• Let the AGA know what’s happening. Reach out to the AGA via the AGA Community, via Twitter, or by emailing Leslie Narramore, the director of regulatory affairs at AGA ([email protected]).
• File a complaint with the State Insurance Commissioner. State Insurance Commissioners are responsible for regulating the insurance industry in their state and can investigate to ensure the laws in their state are being followed and providers and patients are being treated fairly. While insurance law and regulation are established at the state level, the insurance commissioners are members of the National Association of Insurance Commissioners (NAIC), which allows them to coordinate insurance regulation among the states and territories. Find out your state’s complaint process because many state insurance commissioners have on online complaint forms. Keep records of all interactions with the insurance company to document that you have attempted to resolve the matter with the payer first.
• File a complaint at the federal level for states without an external review process. If your state doesn’t have an external review process that meets the minimum consumer protection standards, the federal government’s Department of Health & Human Services oversees an external review process for health insurance companies in your state. See www.healthcare.gov/appeal-insurance-company-decision/external-review/ for more information. In states where the federal government oversees the process, insurance companies may choose to participate in an HHS-administered process or contract with independent review organizations. If your plan doesn’t participate in a state or HHS-Administered Federal External Review Process, your health plan must contract with an independent review organization.

Dr. Guha is with the University of Texas Health Science Center in Houston. Dr. Upchurch is with Adena Health System in Chillicothe, Ohio. Both are AGA Coverage and Reimbursement Subcommittee members. The authors have no conflicts to declare.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The following is a preview of a recent popular clinical discussion:

From John Fang, MD: Update on feeding tubes: Indications and troubleshooting complications.

Gastroenterologists are uniquely positioned to manage individuals with feeding tubes as their training underscores principles in digestion, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require both right education and experience. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Questions:

1. Are gastroenterologist best suited for placement and management of feeding tubes (vs. interventional radiology or surgery)?

2. Are gastroenterologists adequately trained place and manage feeding tubes?

3. What are the most difficult complication(s) of feeding tubes to manage?

The conversation stems from the February In Focus article from The New Gastroenterologist, “Update on feeding tubes: Indications and troubleshooting complications.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/23639.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The following is a preview of a recent popular clinical discussion:

From John Fang, MD: Update on feeding tubes: Indications and troubleshooting complications.

Gastroenterologists are uniquely positioned to manage individuals with feeding tubes as their training underscores principles in digestion, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require both right education and experience. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Questions:

1. Are gastroenterologist best suited for placement and management of feeding tubes (vs. interventional radiology or surgery)?

2. Are gastroenterologists adequately trained place and manage feeding tubes?

3. What are the most difficult complication(s) of feeding tubes to manage?

The conversation stems from the February In Focus article from The New Gastroenterologist, “Update on feeding tubes: Indications and troubleshooting complications.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/23639.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community to seek advice from colleagues about therapy and disease management options, best practices, and diagnoses. The following is a preview of a recent popular clinical discussion:

From John Fang, MD: Update on feeding tubes: Indications and troubleshooting complications.

Gastroenterologists are uniquely positioned to manage individuals with feeding tubes as their training underscores principles in digestion, nutrition support, and enteral tube placement. Adequate management of individuals with feeding tubes and, importantly, the complications that arise from feeding tube use and placement require both right education and experience. Therefore, gastroenterologists are well suited to both place and manage individuals with feeding tubes in the long term.

Questions:

1. Are gastroenterologist best suited for placement and management of feeding tubes (vs. interventional radiology or surgery)?

2. Are gastroenterologists adequately trained place and manage feeding tubes?

3. What are the most difficult complication(s) of feeding tubes to manage?

The conversation stems from the February In Focus article from The New Gastroenterologist, “Update on feeding tubes: Indications and troubleshooting complications.”

See how AGA members responded and join the discussion: https://community.gastro.org/posts/23639.