Kerry Dooley Young

A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

A Food and Drug Administration advisory panel voted 14-2 against recommending approval of a supplemental New Drug Application for empagliflozin (Jardiance) as an adjunct to insulin therapy to improve glycemic control in adults with type 1 diabetes. The drug is already is approved for people with type 2 diabetes.

Members of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee cited persisting concerns about the risk for diabetic ketoacidosis (DKA) seen with the drug, as well as the limited pool of evidence Boehringer Ingelheim presented. Patients with type 1 diabetes are at increased risk for DKA.

The agency said it typically gets two major studies to support applications for drug approvals, but the application reviewed Nov. 13 rested largely on a single phase 3 trial, in which 241 people with type 1 diabetes took a low dose (2.5 mg) of empagliflozin for about 6 months. Panelists repeatedly objected to the paucity of data they had to consider this expanded approval.

“We owe it to patients with type 1 diabetes to do this right,” said Brendan M. Everett, MD, MPH, of Harvard Medical School, Boston, who served as a panelist. “It’s out of respect for them that I voted no.”

Boehringer Ingelheim, and members of the public argued that people with type 1 diabetes want access to new medicines such as empagliflozin that already are available for people with type 2 diabetes. The agency approved the drug in 2014 at doses of 10 mg and 25 mg as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. In 2016, it approved a new indication for empagliflozin for reducing risk of cardiovascular death in people with type 2 disease.

The panelists said they were sympathetic to that point of view, but stressed the need for further larger studies of empagliflozin in people with type 1 diabetes.

“I do think this is promising,” said panelist Michael Blaha, MD, MPH, of Johns Hopkins University, Baltimore. “But I’m not sure we are here to evaluate promising things. We’re here to evaluate proven things.”

The FDA advisers also said there was a need for greater clarity about reporting of adverse events in testing of this drug. The FDA reviewers reported disagreements with Boehringer about some cases classified as “unlikely ketoacidosis but ketosis” in the study.

“Some events adjudicated as ‘unlikely ketoacidosis but ketosis’ were clinically significant serious events requiring hospitalizations and prompt intervention, such as discontinuation of study drug,” wrote Mahtab Niyyati, MD, an FDA clinical reviewer, in her slides for the meeting.

The FDA is not obliged to accept the suggestions of its advisory panels, but it often does.

The agency did not ask the panel to weigh in directly on whether to approve the drug. Instead, the question put to the panel for a vote was whether the available data suggest that the benefits outweigh the risks of empagliflozin and support approval of a 2.5-mg dose as an adjunct to insulin for people with type 1 diabetes.

Empagliflozin is part of the sodium-glucose cotransporter 2 (SGLT2) inhibitor class of medicines, already known to have a risk for DKA, the agency noted in its briefing document for the meeting. DKA occurs as a result of insulin deficiency and subsequent ketogenesis.

There are no SGLT2 inhibitors approved for type 1 diabetes, the staff said in the review. The agency has rebuffed recent bids by makers of other SGLT2 drugs for people with type 1 diabetes. In July, AstraZeneca said the FDA had not approved its application for use of dapagliflozin (Farxiga) as an adjunct treatment to insulin to improve glycemic control in adult patients with type1 diabetes, when insulin alone does not provide adequate glycemic control. AstraZeneca said it was working with the agency on issues raised in the response letter it received.

In March, the FDA blocked a bid by Sanofi for approval of its investigational SGLT1/2 inhibitor, sotagliflozin (Zynquista) for use in people with type 1 diabetes. A panel had voted 8-8 in January on a question about the additional approval for this drug.

At the Nov. 13 meeting, panel members offered comments about the potential design of a new test for empagliflozin in type 1 diabetes, including a suggestion for a 2-year trial.

Anna McCollister-Slipp, the consumer representative on the FDA panel, cast one of the two votes in favor of use of the drug for people with type 1 diabetes. She said the agency needed to press for more research in this field but also argued that patients can manage the risks of treatments they find valuable. She cited, as an example, how she has stuck with an insulin pump to manage her own type 1 diabetes, despite having setbacks with the device that sent her to the emergency department.

The other vote in support of the empagliflozin application came from panelist Kashif M. Munir, MD, medical director of the University of Maryland Center for Diabetes and Endrocrinology, Baltimore. In explaining his vote, Dr. Munir noted that he and other physicians already are prescribing medications such as empagliflozin for people with type 1 diabetes, even though it is an off-label use. Boehringer’s strategy of using a lower dose of the drug for this group of patients would mean a reduction in effectiveness but also would lower the risk for side effects.

“Some of us do use existing medications” and have patients take partial doses, Dr. Munir said, adding that the current off-label use of the drug persuaded him to vote in favor of expanded approval, despite his concerns about the data.

Empagliflozin given at 2.5 mg resulted in a statistically significant difference of 0.26% in change in hemoglobin HbA_1c at week 26, compared with placebo, said Roberto Crackel, PhD, an FDA mathematical statistician, during the presentation. There was a numerically small benefit in body weight and systolic blood pressure, but no benefit in reducing hypoglycemic events, he said.

In concluding, the agency’s presentation, Dr. Niyyati presented a slide depicting potential risk and benefit for empagliflozin with 6 months and then 6.5 years of follow-up. It showed that in terms of the benefit of HbA_1c control, there is a potential but undemonstrated reduction in the risk of microvascular complications at 6 months and an estimated 2.8% reduction in microvascular complications after 6.5 years.

In terms of risk of DKA, there are limited data with unstable estimates, ranging to perhaps as many as 468 additional patients-with-events per 10,000 patients at the 6-month point. By the 6.5-year mark, treating 10,000 patients could result in 1,494 additional events.

In a statement issued after the panel’s vote, Boehringer and its partner on empagliflozin, Eli Lilly, stressed the benefit seen with the drug, a statistically significant reduction in HbA_1c (0.28%), compared with insulin given with a matched placebo in adults with type 1 diabetes. Secondary endpoints of the trial demonstrated reductions in weight (1.8 kg) and systolic blood pressure (2.1 mm Hg), compared with insulin plus placebo, the companies said.

“We continue to believe the totality of data from the EASE [Empagliflozin as Adjunctive to Insulin Therapy] program indicates a favorable benefit-risk profile for empagliflozin 2.5 mg in adults with type 1 diabetes and look forward to continuing to work with the FDA in this review process,” said Mohamed Eid, MD, MPH, vice president, clinical development & medical affairs, cardiometabolism & respiratory medicine, Boehringer Ingelheim, in a statement.

Speaking as a member of the public, Kelly L. Close, founder of the diaTribe Foundation, urged the FDA to “think creatively” about approval of the drug.” Many people already are using empagliflozin off label, she said. An FDA approval would help physicians and their patients manage the risks of this medicine. Without such help, patients may be needlessly exposed to harm, she argued.

“That’s what happens with popular unregulated drugs that payers cover, and we know that many, many payers are covering this drug for people with type 1,” she said.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen’s health research group, made the opposing argument during the public session. The trial, in which 241 took the low dose of the drug and 241 on placebo, was “underpowered” in Dr. Wolfe’s view. He also stressed the issue that the FDA had raised about adjudication of the cases of side effects.

An FDA approval of the 2.5-mg dose would send “a dangerous false green signal to those doctors who are already prescribing off-label” drugs in SGLT2 inhibitor class, he said.

That would foster a misleading perception “that we have found the sweet spot” balancing safety and risk, he added. “I can’t see how the FDA or the advisory committee would suggest approval” of empagliflozin for type 1 diabetes.”

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

WASHINGTON – The practice of medicine needs a major reset to address the stresses that lead to clinician burnout, a condition now estimated to affect a third to a half of clinicians in the United States, according to a report from an influential federal panel.

The National Academy of Medicine (NAM) on Oct. 23 released a report, “Taking Action Against Clinician Burnout: A Systems Approach to Professional Well-Being.” The report calls for a broad and unified approach to tackling the root causes of burnout.

There must be a concerted effort by leaders of many fields of health care to create less stressful workplaces for clinicians, Pascale Carayon, PhD, cochair of the NAM committee that produced the report, said during the NAM press event.

“This is not an easy process,” said Dr. Carayon, a researcher into patient safety issues at the University of Wisconsin–Madison. “There is no single solution.”

The NAM report assigns specific tasks to many different participants in health care through a six-goal approach, as described below.

–Create positive workplaces. Leaders of health care systems should consider how their business and management decisions will affect clinicians’ jobs, taking into account the potential to add to their levels of burnout. Executives need to continuously monitor and evaluate the extent of burnout in their organizations, and report on this at least annually.

–Address burnout in training and in clinicians’ early years. Medical, nursing, and pharmacy schools should consider steps such as monitoring workload, implementing pass-fail grading, improving access to scholarships and affordable loans, and creating new loan repayment systems.

–Reduce administrative burden. Federal and state bodies and organizations such as the National Quality Forum should reconsider how their regulations and recommendations contribute to burnout. Organizations should seek to eliminate tasks that do not improve the care of patients.

–Improve usability and relevance of health information technology (IT). Medical organizations should develop and buy systems that are as user-friendly and easy to operate as possible. They also should look to use IT to reduce documentation demands and automate nonessential tasks.

–Reduce stigma and improve burnout recovery services. State officials and legislative bodies should make it easier for clinicians to use employee assistance programs, peer support programs, and mental health providers without the information being admissible in malpractice litigation. The report notes the recommendations from the Federation of State Medical Boards, American Medical Association, and the American Psychiatric Association on limiting inquiries in licensing applications about a clinician’s mental health. Questions should focus on current impairment rather than reach well into a clinician’s past.

–Create a national research agenda on clinician well-being. By the end of 2020, federal agencies – including the Agency for Healthcare Research and Quality, the National Institute for Occupational Safety and Health, the Health Resources and Services Administration, and the U.S. Department of Veterans Affairs – should develop a coordinated research agenda on clinician burnout, the report said.

In casting a wide net and assigning specific tasks, the NAM report seeks to establish efforts to address clinician burnout as a broad and shared responsibility. It would be too easy for different medical organizations to depict addressing burnout as being outside of their responsibilities, Christine K. Cassel, MD, the cochair of the NAM committee that produced the report, said during the press event.

Delicia M. Haynes, MD, wants the Florida Board of Medicine to take another look at how its licensing applications query physicians about their mental health history. Her state’s board is one of several nationwide that has, in recent years, mulled whether the phrasing of its questions poses an unintended hurdle for physicians who need help for conditions such as depression.

Courtesy of Family First Health Center

The Federation of State Medical Boards (FSMB) recommends limiting such queries, if they must be asked, to questions about potential current impairment. But the Florida license application takes a more sweeping approach that may discourage physicians from seeking treatment, Dr. Haynes, founder and CEO of Family First Health Center in Daytona Beach, Fla., said in a video. She describes herself as a direct primary care physician.

In the video, which was posted on YouTube in January, 2019, Dr. Haynes discussed her own experience with having been treated for depression and then needing to report that to the state board. Florida’s license application asks if physicians have been treated within the past 5 years for a mental disorder that has impaired the ability to practice medicine. Those who have had such a condition may need to give the board an explanation providing the names of the physicians, therapists, and counselors they have seen, as well as details and dates for the institutions where they received treatment.

State medical boards play a critical role in protecting people from physicians whose current mental health conditions may risk harming patients, Dr. Haynes said. But they must balance that against the consequences of overly intrusive questioning. Florida’s current application wording may deter physicians from seeking care if they develop conditions such as depression, she said.

“It’s the fear of what’s going to happen if I have to check yes,” Dr. Haynes said in her YouTube video. Physicians will wonder how getting treatment could put their license and their employment at risk, she added.

“It’s really important that [state medical boards] are asking the questions that matter and those questions are questions that talk about impairment, and not just having a history,” Dr. Haynes said.

Members of Florida’s board of medicine last year favorably discussed making such a change during a rules/legislative committee meeting, but have not yet implemented it. The board has postponed further discussion of this topic until its December meeting, said Brad Dalton, a spokesman for the Florida Department of Health.

Dr. Haynes said in an email that she will continue to press for changes in her state’s licensing application.

There’s been a wave of reconsideration of these kinds of questions, spurred by FSMB efforts, which included the board’s offering specific advice to state medical boards about questions on licensing applications as part of a set of recommendations on addressing physician wellness and burnout last year in a report.

Boards have the option of omitting or dropping specific inquiries about mental health. But if they choose to retain this question, FSMB recommends using this phrasing: “Are you currently suffering from any condition for which you are not being appropriately treated that impairs your judgment or that would otherwise adversely affect your ability to practice medicine in a competent, ethical and professional manner? (Yes/No)” the report says.

The staff of the Medical Board of California cited FSMB’s recommendation in a January 2019 report about revising the state’s approach to asking physicians about their mental health. In May 2019, the board voted unanimously to revise its questions on physicians’ mental health, narrowing its inquiry on the licensing application to focus on current impairment.

“There are many doctors who do not seek treatment or find it threatening to seek treatment, because they are concerned that they may lose their license,” Peter Yellowlees, MBBS, MD, chief wellness officer and a professor of psychiatry at University of California, Davis, said in a public comment offered at the meeting. “This is ultimately all about patient safety.”

In addition to California and Florida, Colorado, Georgia, Massachusetts, Minnesota, Mississippi and Oklahoma have made recent drives to reconsider the phrasing of the mental health question, said Joe Knickrehm, a spokesman for the FSMB. Over the past few years, Kentucky, New Hampshire, New Mexico, North Carolina, North Dakota, Ohio, Vermont and Washington have made changes to their licensing questions, he added.

Still, state boards are not moving quickly enough to remove or revise these questions about mental health, said Katherine J. Gold, MD MSW, associate professor in the department of family medicine at University of Michigan, Ann Arbor. She has studied how these queries can deter physicians from seeking treatment for mental illness. A past treatment for postpartum depression may have no bearing on a physician’s practice, yet members of many state medical boards hesitate to alter their approach, she noted.

Groups including the American Medical Association (AMA) and the American Psychiatric Association also have pushed in recent years for changes in state rules about what a physician has to disclose about mental health, with the FSMB taking a lead in these efforts. In many cases, physicians face questions about their mental health that are beyond the limits of standards set by the Americans With Disabilities Act, according to an article published this year in the FSMB’s Journal of Medical Regulation. As of 2017, a review of questions on initial licensure applications for all 50 states and the District of Columbia showed that 32 licensing boards ask questions beyond the limits of ADA standards, the article said.

Consequences of “reporting stable and easily treatable conditions such as anxiety or depression to a state licensing board can range from a physician simply being required to submit a letter from their primary care provider documenting fitness to practice, to a request to appear before the board, to being required to undergo and pay for an examination by a board-appointed physician,” wrote Catherine M. Welcher, an AMA senior policy analyst, and coauthors of the paper, including Humayun J. Chaudhry, DO, FSMB’s CEO.
 

Nearly 40% of physicians surveyed about medical licensing questions (2,325 of 5,829) indicated they would be reluctant to seek formal medical care for a mental health condition because of potential repercussions, Liselotte N. Dyrbye, MD, and coauthors reported in 2017 in the Mayo Clinic Proceedings.

“You’re sort of stuck. You recognize you have a problem and you want to seek care so that you can get better, but if you do that, you might have to tell the board,” Dr. Dyrbye said in an interview. “You could be mandated potentially to have an outside psychiatric evaluation, to have your personal medical records reviewed by people other than your personal physician.”

Rising levels of burnout among physicians make it critical to remove obstacles to care, said Arthur S. Hengerer, MD, a former chair of the FSMB who has been a leader in efforts to revise medical licensing questions.

Delicia M. Haynes, MD, wants the Florida Board of Medicine to take another look at how its licensing applications query physicians about their mental health history. Her state’s board is one of several nationwide that has, in recent years, mulled whether the phrasing of its questions poses an unintended hurdle for physicians who need help for conditions such as depression.

Courtesy of Family First Health Center

The Federation of State Medical Boards (FSMB) recommends limiting such queries, if they must be asked, to questions about potential current impairment. But the Florida license application takes a more sweeping approach that may discourage physicians from seeking treatment, Dr. Haynes, founder and CEO of Family First Health Center in Daytona Beach, Fla., said in a video. She describes herself as a direct primary care physician.

In the video, which was posted on YouTube in January, 2019, Dr. Haynes discussed her own experience with having been treated for depression and then needing to report that to the state board. Florida’s license application asks if physicians have been treated within the past 5 years for a mental disorder that has impaired the ability to practice medicine. Those who have had such a condition may need to give the board an explanation providing the names of the physicians, therapists, and counselors they have seen, as well as details and dates for the institutions where they received treatment.

State medical boards play a critical role in protecting people from physicians whose current mental health conditions may risk harming patients, Dr. Haynes said. But they must balance that against the consequences of overly intrusive questioning. Florida’s current application wording may deter physicians from seeking care if they develop conditions such as depression, she said.

“It’s the fear of what’s going to happen if I have to check yes,” Dr. Haynes said in her YouTube video. Physicians will wonder how getting treatment could put their license and their employment at risk, she added.

“It’s really important that [state medical boards] are asking the questions that matter and those questions are questions that talk about impairment, and not just having a history,” Dr. Haynes said.

Members of Florida’s board of medicine last year favorably discussed making such a change during a rules/legislative committee meeting, but have not yet implemented it. The board has postponed further discussion of this topic until its December meeting, said Brad Dalton, a spokesman for the Florida Department of Health.

Dr. Haynes said in an email that she will continue to press for changes in her state’s licensing application.

There’s been a wave of reconsideration of these kinds of questions, spurred by FSMB efforts, which included the board’s offering specific advice to state medical boards about questions on licensing applications as part of a set of recommendations on addressing physician wellness and burnout last year in a report.

Boards have the option of omitting or dropping specific inquiries about mental health. But if they choose to retain this question, FSMB recommends using this phrasing: “Are you currently suffering from any condition for which you are not being appropriately treated that impairs your judgment or that would otherwise adversely affect your ability to practice medicine in a competent, ethical and professional manner? (Yes/No)” the report says.

The staff of the Medical Board of California cited FSMB’s recommendation in a January 2019 report about revising the state’s approach to asking physicians about their mental health. In May 2019, the board voted unanimously to revise its questions on physicians’ mental health, narrowing its inquiry on the licensing application to focus on current impairment.

“There are many doctors who do not seek treatment or find it threatening to seek treatment, because they are concerned that they may lose their license,” Peter Yellowlees, MBBS, MD, chief wellness officer and a professor of psychiatry at University of California, Davis, said in a public comment offered at the meeting. “This is ultimately all about patient safety.”

In addition to California and Florida, Colorado, Georgia, Massachusetts, Minnesota, Mississippi and Oklahoma have made recent drives to reconsider the phrasing of the mental health question, said Joe Knickrehm, a spokesman for the FSMB. Over the past few years, Kentucky, New Hampshire, New Mexico, North Carolina, North Dakota, Ohio, Vermont and Washington have made changes to their licensing questions, he added.

Still, state boards are not moving quickly enough to remove or revise these questions about mental health, said Katherine J. Gold, MD MSW, associate professor in the department of family medicine at University of Michigan, Ann Arbor. She has studied how these queries can deter physicians from seeking treatment for mental illness. A past treatment for postpartum depression may have no bearing on a physician’s practice, yet members of many state medical boards hesitate to alter their approach, she noted.

Groups including the American Medical Association (AMA) and the American Psychiatric Association also have pushed in recent years for changes in state rules about what a physician has to disclose about mental health, with the FSMB taking a lead in these efforts. In many cases, physicians face questions about their mental health that are beyond the limits of standards set by the Americans With Disabilities Act, according to an article published this year in the FSMB’s Journal of Medical Regulation. As of 2017, a review of questions on initial licensure applications for all 50 states and the District of Columbia showed that 32 licensing boards ask questions beyond the limits of ADA standards, the article said.

Consequences of “reporting stable and easily treatable conditions such as anxiety or depression to a state licensing board can range from a physician simply being required to submit a letter from their primary care provider documenting fitness to practice, to a request to appear before the board, to being required to undergo and pay for an examination by a board-appointed physician,” wrote Catherine M. Welcher, an AMA senior policy analyst, and coauthors of the paper, including Humayun J. Chaudhry, DO, FSMB’s CEO.
 

Nearly 40% of physicians surveyed about medical licensing questions (2,325 of 5,829) indicated they would be reluctant to seek formal medical care for a mental health condition because of potential repercussions, Liselotte N. Dyrbye, MD, and coauthors reported in 2017 in the Mayo Clinic Proceedings.

“You’re sort of stuck. You recognize you have a problem and you want to seek care so that you can get better, but if you do that, you might have to tell the board,” Dr. Dyrbye said in an interview. “You could be mandated potentially to have an outside psychiatric evaluation, to have your personal medical records reviewed by people other than your personal physician.”

Rising levels of burnout among physicians make it critical to remove obstacles to care, said Arthur S. Hengerer, MD, a former chair of the FSMB who has been a leader in efforts to revise medical licensing questions.

Delicia M. Haynes, MD, wants the Florida Board of Medicine to take another look at how its licensing applications query physicians about their mental health history. Her state’s board is one of several nationwide that has, in recent years, mulled whether the phrasing of its questions poses an unintended hurdle for physicians who need help for conditions such as depression.

Courtesy of Family First Health Center

The Federation of State Medical Boards (FSMB) recommends limiting such queries, if they must be asked, to questions about potential current impairment. But the Florida license application takes a more sweeping approach that may discourage physicians from seeking treatment, Dr. Haynes, founder and CEO of Family First Health Center in Daytona Beach, Fla., said in a video. She describes herself as a direct primary care physician.

In the video, which was posted on YouTube in January, 2019, Dr. Haynes discussed her own experience with having been treated for depression and then needing to report that to the state board. Florida’s license application asks if physicians have been treated within the past 5 years for a mental disorder that has impaired the ability to practice medicine. Those who have had such a condition may need to give the board an explanation providing the names of the physicians, therapists, and counselors they have seen, as well as details and dates for the institutions where they received treatment.

State medical boards play a critical role in protecting people from physicians whose current mental health conditions may risk harming patients, Dr. Haynes said. But they must balance that against the consequences of overly intrusive questioning. Florida’s current application wording may deter physicians from seeking care if they develop conditions such as depression, she said.

“It’s the fear of what’s going to happen if I have to check yes,” Dr. Haynes said in her YouTube video. Physicians will wonder how getting treatment could put their license and their employment at risk, she added.

“It’s really important that [state medical boards] are asking the questions that matter and those questions are questions that talk about impairment, and not just having a history,” Dr. Haynes said.

Members of Florida’s board of medicine last year favorably discussed making such a change during a rules/legislative committee meeting, but have not yet implemented it. The board has postponed further discussion of this topic until its December meeting, said Brad Dalton, a spokesman for the Florida Department of Health.

Dr. Haynes said in an email that she will continue to press for changes in her state’s licensing application.

There’s been a wave of reconsideration of these kinds of questions, spurred by FSMB efforts, which included the board’s offering specific advice to state medical boards about questions on licensing applications as part of a set of recommendations on addressing physician wellness and burnout last year in a report.

Boards have the option of omitting or dropping specific inquiries about mental health. But if they choose to retain this question, FSMB recommends using this phrasing: “Are you currently suffering from any condition for which you are not being appropriately treated that impairs your judgment or that would otherwise adversely affect your ability to practice medicine in a competent, ethical and professional manner? (Yes/No)” the report says.

The staff of the Medical Board of California cited FSMB’s recommendation in a January 2019 report about revising the state’s approach to asking physicians about their mental health. In May 2019, the board voted unanimously to revise its questions on physicians’ mental health, narrowing its inquiry on the licensing application to focus on current impairment.

“There are many doctors who do not seek treatment or find it threatening to seek treatment, because they are concerned that they may lose their license,” Peter Yellowlees, MBBS, MD, chief wellness officer and a professor of psychiatry at University of California, Davis, said in a public comment offered at the meeting. “This is ultimately all about patient safety.”

In addition to California and Florida, Colorado, Georgia, Massachusetts, Minnesota, Mississippi and Oklahoma have made recent drives to reconsider the phrasing of the mental health question, said Joe Knickrehm, a spokesman for the FSMB. Over the past few years, Kentucky, New Hampshire, New Mexico, North Carolina, North Dakota, Ohio, Vermont and Washington have made changes to their licensing questions, he added.

Still, state boards are not moving quickly enough to remove or revise these questions about mental health, said Katherine J. Gold, MD MSW, associate professor in the department of family medicine at University of Michigan, Ann Arbor. She has studied how these queries can deter physicians from seeking treatment for mental illness. A past treatment for postpartum depression may have no bearing on a physician’s practice, yet members of many state medical boards hesitate to alter their approach, she noted.

Groups including the American Medical Association (AMA) and the American Psychiatric Association also have pushed in recent years for changes in state rules about what a physician has to disclose about mental health, with the FSMB taking a lead in these efforts. In many cases, physicians face questions about their mental health that are beyond the limits of standards set by the Americans With Disabilities Act, according to an article published this year in the FSMB’s Journal of Medical Regulation. As of 2017, a review of questions on initial licensure applications for all 50 states and the District of Columbia showed that 32 licensing boards ask questions beyond the limits of ADA standards, the article said.

Consequences of “reporting stable and easily treatable conditions such as anxiety or depression to a state licensing board can range from a physician simply being required to submit a letter from their primary care provider documenting fitness to practice, to a request to appear before the board, to being required to undergo and pay for an examination by a board-appointed physician,” wrote Catherine M. Welcher, an AMA senior policy analyst, and coauthors of the paper, including Humayun J. Chaudhry, DO, FSMB’s CEO.
 

Nearly 40% of physicians surveyed about medical licensing questions (2,325 of 5,829) indicated they would be reluctant to seek formal medical care for a mental health condition because of potential repercussions, Liselotte N. Dyrbye, MD, and coauthors reported in 2017 in the Mayo Clinic Proceedings.

“You’re sort of stuck. You recognize you have a problem and you want to seek care so that you can get better, but if you do that, you might have to tell the board,” Dr. Dyrbye said in an interview. “You could be mandated potentially to have an outside psychiatric evaluation, to have your personal medical records reviewed by people other than your personal physician.”

Rising levels of burnout among physicians make it critical to remove obstacles to care, said Arthur S. Hengerer, MD, a former chair of the FSMB who has been a leader in efforts to revise medical licensing questions.

WASHINGTON – The federal official who helps oversee Medicare’s use of quality measures predicted a continued emphasis on patient-reported outcomes in the assessments of physician performance.

Reena Duseja, MD, chief medical officer for quality measurement at the Centers for Medicare & Medicaid Services, said she has seen “more emphasis” in her 2 years with the agency in collecting outcome measures, including ones reported by patients. In doing this, CMS officials are also looking to identify the core elements that willl be part of patient-reported outcomes (PROs).

“We really have to get better at standardization,” Dr. Duseja said during a policy summit sponsored by the National Comprehensive Cancer Network (NCCN). “There is room for improvement there. We’re continuing to think of ways that we can support that.”

She also said the CMS is working, in general, to try to give physicians feedback sooner on how they are faring on measurements.

“The commitment of our agency is trying to think about how we collect data in a way that shortens the cycle of measure development” and speeds the delivery of this data back to providers, Dr. Duseja said.

Her fellow panelists discussed the difficulties in designing PRO measures, including the need to account for special challenges for patients living in or near poverty. Avoiding emergency department visits and hospitalizations, for example, may be a key priority for people who are paid hourly wages, said Kashyap Patel, MD, managing partner of Carolina Blood and Cancer Care in Rock Hill, S.C. These patients will not only face the inconvenience and cost of a hospital stay, but will also lose wages from missed work. He urged policymakers to take these factors into consideration in designing quality measures, and not to forget that “there is a human being behind this.”

Ronald S. Walters, MD, associate head of the Institute for Cancer Care Innovation at the University of Texas MD Anderson Cancer Center, and chair of NCCN’s board of directors, cautioned against continued attempts to devise a “Nirvana” list of outcome measures that can be universally applied. Instead, payers may be better off with a “mix and match” approach. Certain measures may be used across the board, such as pain and quality of life metrics, while other measures could be more tailored.

Dr. Walters also called out a missed opportunity to tie PROs to Medicare payment in the area of chimeric antigen receptor (CAR) T-cell therapy.

In 2018, the CMS indicated it was considering the use of PROs in connection with CAR T-cell payment. The CMS asked its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to consider the role of PROs in connection with payment for CAR T-cell therapy. At an August 2018 meeting, MEDCAC panelists generally expressed confidence in PROs in a series of votes about the use of this approach to quality measurement in cancer trials.

But drugmakers and physician groups raised strong objections at the MEDCAC meeting. In its national coverage decision on CAR T, issued in August 2019, the CMS said it had received many comments on PROs “ranging from support of their collection to recommendations for additional assessment tools to request to remove PRO requirements.” The CMS opted at this time to encourage participation in the Center for International Blood and Marrow Transplantation Research (CIBMTR) database “that currently collects health outcomes (and aims to collect patient reported outcomes in the future) on patients who have received CAR T-cell treatments.”

For Dr. Walters, this setback for the use of PROs in CAR T therapy payment is telling, as the treatment is known to produce serious side effects and is administered in well-controlled circumstances.

“If you can’t organize collecting patient-reported outcomes after CAR T cell, that kind of tells you the state of where we are on collecting them on everybody,” Dr. Walters said.

WASHINGTON – The federal official who helps oversee Medicare’s use of quality measures predicted a continued emphasis on patient-reported outcomes in the assessments of physician performance.

Reena Duseja, MD, chief medical officer for quality measurement at the Centers for Medicare & Medicaid Services, said she has seen “more emphasis” in her 2 years with the agency in collecting outcome measures, including ones reported by patients. In doing this, CMS officials are also looking to identify the core elements that willl be part of patient-reported outcomes (PROs).

“We really have to get better at standardization,” Dr. Duseja said during a policy summit sponsored by the National Comprehensive Cancer Network (NCCN). “There is room for improvement there. We’re continuing to think of ways that we can support that.”

She also said the CMS is working, in general, to try to give physicians feedback sooner on how they are faring on measurements.

“The commitment of our agency is trying to think about how we collect data in a way that shortens the cycle of measure development” and speeds the delivery of this data back to providers, Dr. Duseja said.

Her fellow panelists discussed the difficulties in designing PRO measures, including the need to account for special challenges for patients living in or near poverty. Avoiding emergency department visits and hospitalizations, for example, may be a key priority for people who are paid hourly wages, said Kashyap Patel, MD, managing partner of Carolina Blood and Cancer Care in Rock Hill, S.C. These patients will not only face the inconvenience and cost of a hospital stay, but will also lose wages from missed work. He urged policymakers to take these factors into consideration in designing quality measures, and not to forget that “there is a human being behind this.”

Ronald S. Walters, MD, associate head of the Institute for Cancer Care Innovation at the University of Texas MD Anderson Cancer Center, and chair of NCCN’s board of directors, cautioned against continued attempts to devise a “Nirvana” list of outcome measures that can be universally applied. Instead, payers may be better off with a “mix and match” approach. Certain measures may be used across the board, such as pain and quality of life metrics, while other measures could be more tailored.

Dr. Walters also called out a missed opportunity to tie PROs to Medicare payment in the area of chimeric antigen receptor (CAR) T-cell therapy.

In 2018, the CMS indicated it was considering the use of PROs in connection with CAR T-cell payment. The CMS asked its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to consider the role of PROs in connection with payment for CAR T-cell therapy. At an August 2018 meeting, MEDCAC panelists generally expressed confidence in PROs in a series of votes about the use of this approach to quality measurement in cancer trials.

But drugmakers and physician groups raised strong objections at the MEDCAC meeting. In its national coverage decision on CAR T, issued in August 2019, the CMS said it had received many comments on PROs “ranging from support of their collection to recommendations for additional assessment tools to request to remove PRO requirements.” The CMS opted at this time to encourage participation in the Center for International Blood and Marrow Transplantation Research (CIBMTR) database “that currently collects health outcomes (and aims to collect patient reported outcomes in the future) on patients who have received CAR T-cell treatments.”

For Dr. Walters, this setback for the use of PROs in CAR T therapy payment is telling, as the treatment is known to produce serious side effects and is administered in well-controlled circumstances.

“If you can’t organize collecting patient-reported outcomes after CAR T cell, that kind of tells you the state of where we are on collecting them on everybody,” Dr. Walters said.

WASHINGTON – The federal official who helps oversee Medicare’s use of quality measures predicted a continued emphasis on patient-reported outcomes in the assessments of physician performance.

Reena Duseja, MD, chief medical officer for quality measurement at the Centers for Medicare & Medicaid Services, said she has seen “more emphasis” in her 2 years with the agency in collecting outcome measures, including ones reported by patients. In doing this, CMS officials are also looking to identify the core elements that willl be part of patient-reported outcomes (PROs).

“We really have to get better at standardization,” Dr. Duseja said during a policy summit sponsored by the National Comprehensive Cancer Network (NCCN). “There is room for improvement there. We’re continuing to think of ways that we can support that.”

She also said the CMS is working, in general, to try to give physicians feedback sooner on how they are faring on measurements.

“The commitment of our agency is trying to think about how we collect data in a way that shortens the cycle of measure development” and speeds the delivery of this data back to providers, Dr. Duseja said.

Her fellow panelists discussed the difficulties in designing PRO measures, including the need to account for special challenges for patients living in or near poverty. Avoiding emergency department visits and hospitalizations, for example, may be a key priority for people who are paid hourly wages, said Kashyap Patel, MD, managing partner of Carolina Blood and Cancer Care in Rock Hill, S.C. These patients will not only face the inconvenience and cost of a hospital stay, but will also lose wages from missed work. He urged policymakers to take these factors into consideration in designing quality measures, and not to forget that “there is a human being behind this.”

Ronald S. Walters, MD, associate head of the Institute for Cancer Care Innovation at the University of Texas MD Anderson Cancer Center, and chair of NCCN’s board of directors, cautioned against continued attempts to devise a “Nirvana” list of outcome measures that can be universally applied. Instead, payers may be better off with a “mix and match” approach. Certain measures may be used across the board, such as pain and quality of life metrics, while other measures could be more tailored.

Dr. Walters also called out a missed opportunity to tie PROs to Medicare payment in the area of chimeric antigen receptor (CAR) T-cell therapy.

In 2018, the CMS indicated it was considering the use of PROs in connection with CAR T-cell payment. The CMS asked its Medicare Evidence Development and Coverage Advisory Committee (MEDCAC) to consider the role of PROs in connection with payment for CAR T-cell therapy. At an August 2018 meeting, MEDCAC panelists generally expressed confidence in PROs in a series of votes about the use of this approach to quality measurement in cancer trials.

But drugmakers and physician groups raised strong objections at the MEDCAC meeting. In its national coverage decision on CAR T, issued in August 2019, the CMS said it had received many comments on PROs “ranging from support of their collection to recommendations for additional assessment tools to request to remove PRO requirements.” The CMS opted at this time to encourage participation in the Center for International Blood and Marrow Transplantation Research (CIBMTR) database “that currently collects health outcomes (and aims to collect patient reported outcomes in the future) on patients who have received CAR T-cell treatments.”

For Dr. Walters, this setback for the use of PROs in CAR T therapy payment is telling, as the treatment is known to produce serious side effects and is administered in well-controlled circumstances.

“If you can’t organize collecting patient-reported outcomes after CAR T cell, that kind of tells you the state of where we are on collecting them on everybody,” Dr. Walters said.

WASHINGTON – Federal officials are considering how they might extend a test of payment approaches meant to spur more coordinated cancer care beyond the program’s current 2021 end date.

Alexandra Chong, PhD, the team lead for the Oncology Care Model at the Center for Medicare and Medicaid Innovation (CMMI), said her agency found strong support for sustaining this kind of effort at “practice transformation.” The Oncology Care Model, which kicked off in 2016, involves about 175 practices and 10 insurers.

“As we look forward, we certainly recognize and appreciate the importance of the impact that [the Oncology Care Model] made and the desire for a continuation, either in an iteration of the current model or a different model,” Dr. Chong said during a panel discussion at a policy summit sponsored by the National Comprehensive Cancer Network (NCCN).

Dr. Chong said the Centers for Medicare & Medicaid Services is aware that there is “a lot of interest” in the future of the program. “We have heard from our practices that this model has been an opportunity for them to provide the care that they really want to provide,” Dr. Chong said.

A fellow panelist at the NCCN event, Kerin Adelson, MD, chief quality officer of Yale’s Smilow Cancer Hospital, New Haven, Conn., pressed for continuation of this kind of a payment test. Smilow has used revenue from the Oncology Care Model program to develop dashboards to measure individual clinicians’ patterns of care and share data with them, Dr. Adelson said.

The changes have been “transformative,” including allowing for hiring of additional support staff, Dr. Adelson said.

“I am terrified about what’s going to happen at the end of the program if there is not another model to transition to,” Dr. Adelson said. “We will potentially be looking at layoffs of these people who are so incredible and have done so much for the care we are giving.”

In May 2019, some of Dr. Chong’s CMMI colleagues published a report in the Journal of the National Cancer Institute about the experiences of clinics participating in the Oncology Care Model. For instance, the U.S. Oncology Network used Monthly Enhanced Oncology Services [MEOS] payments through the program for new hires such as navigators, social workers, additional advanced practice providers, “and even data analysts,” according to the report.

Still, there have been “growing pains” with the start-up of the model, Dr. Chong said. Fellow participants on the NCCN panel cited the introduction of costly new drugs as one wrinkle in the early days of the Oncology Care Model. Another is that physicians in practices signed up for the program sometimes are unaware of it.

The American Society of Clinical Oncology also is advocating for a continuation of a model along the lines of the Oncology Care Model.

“It would be good to see it continue. We’re certainly supportive of continuing to work on this model and refine it and see where it goes,” Stephen S. Grubbs, MD, ASCO’s vice president for clinical affairs, said in an interview.

Dr. Grubbs said that CMS’s Oncology Care Model could not be greatly expanded in its current form, as it imposes a steep administrative burden for both practices who participate, as well as for CMMI. The current model also does not serve smaller and rural practices well, he said.

ASCO is refining its own proposal for an alternative payment approach. The group plans to present its Patient-Centered Oncology Payment (PCOP) model, first published in 2015, before an influential federal advisory group, the Physician-Focused Payment Model Technical Advisory Committee (PTAC), at a meeting in 2020.

WASHINGTON – Federal officials are considering how they might extend a test of payment approaches meant to spur more coordinated cancer care beyond the program’s current 2021 end date.

Alexandra Chong, PhD, the team lead for the Oncology Care Model at the Center for Medicare and Medicaid Innovation (CMMI), said her agency found strong support for sustaining this kind of effort at “practice transformation.” The Oncology Care Model, which kicked off in 2016, involves about 175 practices and 10 insurers.

“As we look forward, we certainly recognize and appreciate the importance of the impact that [the Oncology Care Model] made and the desire for a continuation, either in an iteration of the current model or a different model,” Dr. Chong said during a panel discussion at a policy summit sponsored by the National Comprehensive Cancer Network (NCCN).

Dr. Chong said the Centers for Medicare & Medicaid Services is aware that there is “a lot of interest” in the future of the program. “We have heard from our practices that this model has been an opportunity for them to provide the care that they really want to provide,” Dr. Chong said.

A fellow panelist at the NCCN event, Kerin Adelson, MD, chief quality officer of Yale’s Smilow Cancer Hospital, New Haven, Conn., pressed for continuation of this kind of a payment test. Smilow has used revenue from the Oncology Care Model program to develop dashboards to measure individual clinicians’ patterns of care and share data with them, Dr. Adelson said.

The changes have been “transformative,” including allowing for hiring of additional support staff, Dr. Adelson said.

“I am terrified about what’s going to happen at the end of the program if there is not another model to transition to,” Dr. Adelson said. “We will potentially be looking at layoffs of these people who are so incredible and have done so much for the care we are giving.”

In May 2019, some of Dr. Chong’s CMMI colleagues published a report in the Journal of the National Cancer Institute about the experiences of clinics participating in the Oncology Care Model. For instance, the U.S. Oncology Network used Monthly Enhanced Oncology Services [MEOS] payments through the program for new hires such as navigators, social workers, additional advanced practice providers, “and even data analysts,” according to the report.

Still, there have been “growing pains” with the start-up of the model, Dr. Chong said. Fellow participants on the NCCN panel cited the introduction of costly new drugs as one wrinkle in the early days of the Oncology Care Model. Another is that physicians in practices signed up for the program sometimes are unaware of it.

The American Society of Clinical Oncology also is advocating for a continuation of a model along the lines of the Oncology Care Model.

“It would be good to see it continue. We’re certainly supportive of continuing to work on this model and refine it and see where it goes,” Stephen S. Grubbs, MD, ASCO’s vice president for clinical affairs, said in an interview.

Dr. Grubbs said that CMS’s Oncology Care Model could not be greatly expanded in its current form, as it imposes a steep administrative burden for both practices who participate, as well as for CMMI. The current model also does not serve smaller and rural practices well, he said.

ASCO is refining its own proposal for an alternative payment approach. The group plans to present its Patient-Centered Oncology Payment (PCOP) model, first published in 2015, before an influential federal advisory group, the Physician-Focused Payment Model Technical Advisory Committee (PTAC), at a meeting in 2020.

WASHINGTON – Federal officials are considering how they might extend a test of payment approaches meant to spur more coordinated cancer care beyond the program’s current 2021 end date.

Alexandra Chong, PhD, the team lead for the Oncology Care Model at the Center for Medicare and Medicaid Innovation (CMMI), said her agency found strong support for sustaining this kind of effort at “practice transformation.” The Oncology Care Model, which kicked off in 2016, involves about 175 practices and 10 insurers.

“As we look forward, we certainly recognize and appreciate the importance of the impact that [the Oncology Care Model] made and the desire for a continuation, either in an iteration of the current model or a different model,” Dr. Chong said during a panel discussion at a policy summit sponsored by the National Comprehensive Cancer Network (NCCN).

Dr. Chong said the Centers for Medicare & Medicaid Services is aware that there is “a lot of interest” in the future of the program. “We have heard from our practices that this model has been an opportunity for them to provide the care that they really want to provide,” Dr. Chong said.

A fellow panelist at the NCCN event, Kerin Adelson, MD, chief quality officer of Yale’s Smilow Cancer Hospital, New Haven, Conn., pressed for continuation of this kind of a payment test. Smilow has used revenue from the Oncology Care Model program to develop dashboards to measure individual clinicians’ patterns of care and share data with them, Dr. Adelson said.

The changes have been “transformative,” including allowing for hiring of additional support staff, Dr. Adelson said.

“I am terrified about what’s going to happen at the end of the program if there is not another model to transition to,” Dr. Adelson said. “We will potentially be looking at layoffs of these people who are so incredible and have done so much for the care we are giving.”

In May 2019, some of Dr. Chong’s CMMI colleagues published a report in the Journal of the National Cancer Institute about the experiences of clinics participating in the Oncology Care Model. For instance, the U.S. Oncology Network used Monthly Enhanced Oncology Services [MEOS] payments through the program for new hires such as navigators, social workers, additional advanced practice providers, “and even data analysts,” according to the report.

Still, there have been “growing pains” with the start-up of the model, Dr. Chong said. Fellow participants on the NCCN panel cited the introduction of costly new drugs as one wrinkle in the early days of the Oncology Care Model. Another is that physicians in practices signed up for the program sometimes are unaware of it.

The American Society of Clinical Oncology also is advocating for a continuation of a model along the lines of the Oncology Care Model.

“It would be good to see it continue. We’re certainly supportive of continuing to work on this model and refine it and see where it goes,” Stephen S. Grubbs, MD, ASCO’s vice president for clinical affairs, said in an interview.

Dr. Grubbs said that CMS’s Oncology Care Model could not be greatly expanded in its current form, as it imposes a steep administrative burden for both practices who participate, as well as for CMMI. The current model also does not serve smaller and rural practices well, he said.

ASCO is refining its own proposal for an alternative payment approach. The group plans to present its Patient-Centered Oncology Payment (PCOP) model, first published in 2015, before an influential federal advisory group, the Physician-Focused Payment Model Technical Advisory Committee (PTAC), at a meeting in 2020.

U.S. regulators canceled a July 31, 2019, advisory committee about lumateperone, an experimental schizophrenia drug that has had some mixed results in testing.

On July 23, the Food and Drug Administration announced the cancellation of the Psychopharmacologic Drugs Advisory Committee meeting it had previously called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.” The FDA said it was continuing to evaluate the application and would, as needed, announce a future meeting on it.

The developer of lumateperone, Intra-Cellular Therapies, issued its own statement on July 23, noting that a meeting had been scheduled with the FDA “shortly” and that an update would be provided after the meeting. The New York–based firm also said it recently had provided additional information to the FDA to meet agency requests. This information was related to “nonclinical studies.”

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said in the July 23 statement. The company also said there may be an extension of the FDA’s Sept. 27, 2019, target action date on the lumateperone application.

Investors viewed this as bad news. Shares of Intra-Cellular on July 23 dropped from an opening price of $11.90 to a closing one of $8.19. On July 29, they closed at $8.12.

Still, it is unclear how the FDA will decide on the lumateperone application and whether the agency will call another advisory committee meeting on it.

Last year, the FDA accepted the application for lumateperone, a once-daily treatment, Intra-Cellular said. The agency had in 2017 given a fast-track designation to lumateperone for the treatment of schizophrenia.


Lumateperone is the lead product for the company. Intra-Cellular describes lumateperone as having a novel mechanism of action, and is said to act on the serotonergic, dopaminergic, and glutamatergic systems.

On the company’s website, Intra-Cellular says three large randomized, double-blind, placebo-controlled trials have been done for lumateperone as a schizophrenia drug. In two of these studies, results for lumateperone at a 60-mg dose showed a “statistically significant separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale or PANSS total score.”

In a recent routine filing with the Securities and Exchange Commission, Intra-Cellular said it was having an “ongoing dialogue” with the FDA about lumateperone. The company in 2016 had announced that, in a phase 3 study known as ITI-007-302, lumateperone had not separated from placebo on the primary endpoint, change from baseline on the PANSS total score, in the predefined patient population. The active control for ITI-007-302, risperidone, did separate from placebo.

In the recent SEC filing, Intra-Cellular said the FDA already has confirmed that the results of ITI-007-302 did not preclude the submission of a new drug application.

Intra-Cellular also said “lumateperone was statistically significantly better than risperidone on key safety and tolerability parameters, and exhibited a safety profile similar to placebo” in the 302 study. Lumateperone’s failure to best placebo in the 302 test was “in part due to an unusually high placebo response at certain sites.”

U.S. regulators canceled a July 31, 2019, advisory committee about lumateperone, an experimental schizophrenia drug that has had some mixed results in testing.

On July 23, the Food and Drug Administration announced the cancellation of the Psychopharmacologic Drugs Advisory Committee meeting it had previously called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.” The FDA said it was continuing to evaluate the application and would, as needed, announce a future meeting on it.

The developer of lumateperone, Intra-Cellular Therapies, issued its own statement on July 23, noting that a meeting had been scheduled with the FDA “shortly” and that an update would be provided after the meeting. The New York–based firm also said it recently had provided additional information to the FDA to meet agency requests. This information was related to “nonclinical studies.”

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said in the July 23 statement. The company also said there may be an extension of the FDA’s Sept. 27, 2019, target action date on the lumateperone application.

Investors viewed this as bad news. Shares of Intra-Cellular on July 23 dropped from an opening price of $11.90 to a closing one of $8.19. On July 29, they closed at $8.12.

Still, it is unclear how the FDA will decide on the lumateperone application and whether the agency will call another advisory committee meeting on it.

Last year, the FDA accepted the application for lumateperone, a once-daily treatment, Intra-Cellular said. The agency had in 2017 given a fast-track designation to lumateperone for the treatment of schizophrenia.


Lumateperone is the lead product for the company. Intra-Cellular describes lumateperone as having a novel mechanism of action, and is said to act on the serotonergic, dopaminergic, and glutamatergic systems.

On the company’s website, Intra-Cellular says three large randomized, double-blind, placebo-controlled trials have been done for lumateperone as a schizophrenia drug. In two of these studies, results for lumateperone at a 60-mg dose showed a “statistically significant separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale or PANSS total score.”

In a recent routine filing with the Securities and Exchange Commission, Intra-Cellular said it was having an “ongoing dialogue” with the FDA about lumateperone. The company in 2016 had announced that, in a phase 3 study known as ITI-007-302, lumateperone had not separated from placebo on the primary endpoint, change from baseline on the PANSS total score, in the predefined patient population. The active control for ITI-007-302, risperidone, did separate from placebo.

In the recent SEC filing, Intra-Cellular said the FDA already has confirmed that the results of ITI-007-302 did not preclude the submission of a new drug application.

Intra-Cellular also said “lumateperone was statistically significantly better than risperidone on key safety and tolerability parameters, and exhibited a safety profile similar to placebo” in the 302 study. Lumateperone’s failure to best placebo in the 302 test was “in part due to an unusually high placebo response at certain sites.”

U.S. regulators canceled a July 31, 2019, advisory committee about lumateperone, an experimental schizophrenia drug that has had some mixed results in testing.

On July 23, the Food and Drug Administration announced the cancellation of the Psychopharmacologic Drugs Advisory Committee meeting it had previously called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.” The FDA said it was continuing to evaluate the application and would, as needed, announce a future meeting on it.

The developer of lumateperone, Intra-Cellular Therapies, issued its own statement on July 23, noting that a meeting had been scheduled with the FDA “shortly” and that an update would be provided after the meeting. The New York–based firm also said it recently had provided additional information to the FDA to meet agency requests. This information was related to “nonclinical studies.”

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said in the July 23 statement. The company also said there may be an extension of the FDA’s Sept. 27, 2019, target action date on the lumateperone application.

Investors viewed this as bad news. Shares of Intra-Cellular on July 23 dropped from an opening price of $11.90 to a closing one of $8.19. On July 29, they closed at $8.12.

Still, it is unclear how the FDA will decide on the lumateperone application and whether the agency will call another advisory committee meeting on it.

Last year, the FDA accepted the application for lumateperone, a once-daily treatment, Intra-Cellular said. The agency had in 2017 given a fast-track designation to lumateperone for the treatment of schizophrenia.


Lumateperone is the lead product for the company. Intra-Cellular describes lumateperone as having a novel mechanism of action, and is said to act on the serotonergic, dopaminergic, and glutamatergic systems.

On the company’s website, Intra-Cellular says three large randomized, double-blind, placebo-controlled trials have been done for lumateperone as a schizophrenia drug. In two of these studies, results for lumateperone at a 60-mg dose showed a “statistically significant separation from placebo on the primary endpoint, the Positive and Negative Syndrome Scale or PANSS total score.”

In a recent routine filing with the Securities and Exchange Commission, Intra-Cellular said it was having an “ongoing dialogue” with the FDA about lumateperone. The company in 2016 had announced that, in a phase 3 study known as ITI-007-302, lumateperone had not separated from placebo on the primary endpoint, change from baseline on the PANSS total score, in the predefined patient population. The active control for ITI-007-302, risperidone, did separate from placebo.

In the recent SEC filing, Intra-Cellular said the FDA already has confirmed that the results of ITI-007-302 did not preclude the submission of a new drug application.

Intra-Cellular also said “lumateperone was statistically significantly better than risperidone on key safety and tolerability parameters, and exhibited a safety profile similar to placebo” in the 302 study. Lumateperone’s failure to best placebo in the 302 test was “in part due to an unusually high placebo response at certain sites.”

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

WASHINGTON – Kim Schrier, MD, the first pediatrician elected to the U.S. House of Representatives, describes her decision to seek a seat in Congress as a natural extension of her work caring for children.

Nick Piegari/MDedge News

Following the 2016 election, she said she became concerned about what she saw as rising threats to the health of families. The Republican congressional majority made several attempts to undo the Affordable Care Act. In an interview with Pediatric News, Dr. Schrier, a Democrat who represents Washington’s 8th district, said she worried about a rollback of the insurance protections the 2010 law created for people with preexisting conditions. She understood the need for these guarantees of access to care both as a physician and as a patient – Dr. Schrier was diagnosed with type 1 diabetes as a teenager.

Her concerns extended beyond the health care and insurance. Efforts to weaken environmental protections could create new risks for children’s health, she said. Dr. Schrier also worried about attempts to erode Roe v. Wade and to reduce funding for programs such as SNAP supplemental food assistance.

“I felt like every one of those elements was under assault and so who better to speak to that than the pediatrician with her own preexisting condition?” she said.

Dr. Schrier currently is the only female physician serving in Congress. “It’s exciting to be here and it’s exciting to bring that lens that no one else really has,” she said.

Still, the decision to run was not easy.

“I’ve left a practice that I love. I had no intention to run for office ever in my life.”

Dr. Schrier earned an undergraduate degree in astrophysics at the University of California, Berkeley. She worked for about a year at the Environmental Protection Agency before earning her medical degree at the University of California, Davis, and completing her residency at Stanford (Calif.) University. She was working as a pediatrician in the Seattle-based Virginia Mason Health System when she decided to run for Congress.

Her husband, David, and son, Sam, are staying on in the family’s home of Sammamish as she settles into her new work as a legislator. She said she returns home often.

“I go back and forth every week. I just didn’t see it working all that well with having them here,” she said. “I work from 8:00 or 9:00 in the morning until 9:00 at night and would never see them anyway.”

Dr. Schrier has long used an insulin pump and glucose monitors to keep her diabetes in check.

“It is a bit more difficult because my days are less predictable” when working in the Capitol, she said. “So I carry granola bars around in my purse.”
 

Bipartisan bill

Dr. Schrier said she is taking her time in deciding on the first health care legislation that she will introduce in the House. She’s considering measures that would focus on children’s health, possibly in connection with nutrition or with protection of those in immigrant communities.

“I’m looking at something that is uniquely me and know that a lot of my colleagues are going to be working on things like affordability of medications and I will partner with them,” she said.

Dr. Schrier said that she supports creating a way for people to buy into Medicare coverage, paying for this government insurance on a sliding scale. The American public is getting more comfortable with the idea of expanding access to Medicare, which “is incredibly popular but now exclusively available for seniors and other selected groups,” she said.

In her view, an expanded Medicare would stand among private insurance options, allowing for a gradual change.

“It’s a way that we could start tomorrow to let people buy in, as opposed to having a 5- or 10-year rollout that something as big and daunting as a Medicare-for-all plan would require,” she said.

But Dr. Schrier said she won’t start her legislative career with such a sweeping goal as a Medicare buy-in bill.

“I think it would be jumping the gun to come in right away with my own health plan because I really want to collaborate” with fellow lawmakers, she said.

Winning Republican support for her future legislation also is important to Dr. Schrier. “I want to make sure that I have the support of a lot of my colleagues,” she said. “I would like to see a successful first bill.

“The advantage of coming at this as a pediatrician and taking on a first bill or bills that relate to children is that both sides of the aisle can get behind what is good for families and children,” Dr. Schrier said. “I think that’s hard to really argue with.”

Dr. Schrier cosponsored her first piece of legislation in February, reaching across the aisle to work with Rep. Dan Newhouse (R-Wash.) to introduce H.R. 1048, a bill to authorize the next phase of a water resource management plan for Washington’s Yakima River basin.

Beyond that effort, Dr. Schrier said she’s seeking areas of common ground with Republican members of her state delegation. She had dinner in January with two Republican members of the Washington delegation – Rep. Cathy McMorris Rodgers and Rep. Jaime Herrera Beutler. Rep. McMorris Rodgers’ website describes her as a leader in the disabilities community and the only member of Congress to give birth three times while in office, while Rep. Herrera Beutler has spoken openly about her daughter’s battle with Potter’s syndrome, in which the kidneys fail to develop.

Within her party, Dr. Schrier is allied with the moderate New Democrat Coalition. Also in the coalition are two fellow physicians, Ami Bera, MD, and Raul Ruiz, MD, both from California. The New Democrat Coalition also has several lawmakers who flipped House seats from Republican control to Democratic in the 2018 election, a group that includes Dr. Schrier and Reps. Jennifer Wexton (D-VA) and Mikie Sherrill (D-NJ). It was the victories of these moderates that gave the Democrats control of the House. Yet, they get far less media attention than do House Democratic freshmen who are politically further to the left. These members, including Rep. Alexandria Ocasio-Cortez (D-N.Y.), tend to hail from districts where Republicans stand little chance of winning.

Dr. Schrier said the Democratic party, and Congress as a whole, should focus on issues such as affordable health care, on which the country can unite.

“If you’re looking for collaboration, that just doesn’t make the headlines and yet it is the absolute best thing for the country,” she said, adding that most Americans have more centrist views. “So we should really be governing to the middle and that’s how we can move our country forward.”

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD. – The risk of brain damage from sickle cell disease (SCD) merits more attention, even with progress made in recent decades to prevent strokes, according to Lori Jordan, MD, PhD, of Vanderbilt University, Nashville, Tenn.

“Whether we can see it or not, the same injury we’ve been talking about in the kidney and the liver and other places is occurring in the brain” with sickle cell disease, Dr. Jordan said at Sickle Cell in Focus, a conference held by the National Institutes of Health.

The concern about long-term brain injury reflects major shifts in SCD treatment. Improved medical care has transformed SCD from a disease that often resulted in an early death to more of a chronic condition, Dr. Jordan said, citing research that shows a survival rate of roughly 99% to age 18 years (Br J Haematol. 2016 Jun;173[6]:927-37).

One of the major success stories in SCD treatment also has been using primary prevention steps to cut the risk of overt stroke at least 10-fold, Dr. Jordan said. Primary prevention includes annual scans with transcranial Doppler ultrasound to identify children with SCD at high risk of stroke.

“What’s not changing is that there is silent injury that accumulates” and can cause lifelong harm, she said. “We want to protect our patients long term so that they can have a successful adult life, not just a successful childhood.”

Research done by one of Dr. Jordan’s colleagues at Vanderbilt, Michael R. DeBaun, MD, showed that regular blood-transfusion therapy significantly reduced the incidence of the recurrence of brain infarct in children with sickle cell anemia. (N Engl J Med. 2014 Aug 21;371[8]:699-710).


But the lessons from the work of Dr. DeBaun and his colleagues with their Silent Cerebral Infarct Multi-Center Clinical (SIT) Trial have not yet been fully adopted, Dr. Jordan said. That’s partly due to the inconvenience and cost of routinely administered blood transfusions to prevent silent cerebral infarcts, which, when used long term, cause side effects, she said.

Dr. Jordan said there’s growing interest in identifying patients at high risk for stroke and moving them toward stem cell transplant, though studies are ongoing. She urged greater attention to the high lifetime costs of strokes and other cerebrovascular complications, particularly in children and young adults.

While some of the brain infarcts are small and don’t result in focal weakness of the body, these “silent infarcts” do produce cognitive effects that reduce function, school performance, employment, and quality of life, she said.

“The injury to the brain is present, whether we can see it or not,” Dr. Jordan said. “In these precious patients, slow cognitive decline isn’t acceptable, frankly.”

Dr. Jordan reported having received funding from the American Heart Association and the National Institutes of Health for stroke prevention studies in SCD.

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.

BETHESDA, MD – While there are experimental treatments such as sevuparin and gene therapy in testing for sickle cell disease (SCD), researchers said this field is lagging because of a lack of funding.

Dr_Microbe/Thinkstock

Yogen Saunthararajah, MD, of the Cleveland Clinic, described what he called a “paltry” landscape of new drugs for SCD at Sickle Cell in Focus, a conference held by the National Institutes of Health.

There are only four main approaches taken by drugs now in clinical testing for addressing the root causes of SCD, despite decades’ worth of research of the genetic and mechanistic underpinnings of this disease, he said.

“It’s pretty sad,” Dr. Saunthararajah said, referring to the quantity of efforts, not their quality.

Within days of his presentation at the conference, one of the drugs he highlighted had officially fallen out of contention. An Oct. 26 post on NIH’s Clinicaltrials.gov site said Incyte had terminated its phase 1 study of INCB059872 in SCD “due to a business decision” not to pursue this indication. Incyte confirmed that it dropped development of INCB059872 for SCD but will continue testing it for other indications, including acute myeloid leukemia (AML).

Dr. Saunthararajah said that work on another approach, using decitabine (Dacogen), for which he has done a phase 1 study, is “struggling,” because of the search for funding.

Two other approaches that Dr. Saunthararajah cited in his presentation appear to remain on track. These are gene therapy and the once-daily voxelotor treatment from Global Blood Therapeutics.

In the field of gene therapy, Sangamo Therapeutics and Sanofi’s Bioverativ in May said the Food and Drug Administration had cleared the way for them to start a phase 1/2 clinical trial for the BIVV003 product that they are developing together. This uses zinc finger nuclease (ZFN) gene-editing technology to modifying a short sequence of the BCL11A gene, with the aim of reactivating fetal hemoglobin.

Bluebird Bio’s LentiGlobin gene therapy has advanced as far as phase 3 for transfusion-dependent beta-thalassemia and phase 1/2 for SCD. In October, the European Medicines Agency accepted the company’s application for approval of LentiGlobin gene therapy for the treatment of adolescents and adults with transfusion-dependent beta-thalassemia (TDT) and a non-beta⁰/beta⁰ genotype. The company has not said when it expects to file with the FDA for approval of this treatment.

In the field of oral therapies, Global Blood Therapeutics has said it’s in discussions with the FDA about a potential accelerated approval of voxelotor. The tablet is meant to inhibit the underlying mechanism that causes sickling of red blood cells. In June, the company completed a planned review of early data from its phase 3 trial, known as the HOPE study.

“On the primary endpoint (the proportion of patients with greater than 1 g/dL increase in hemoglobin versus baseline), a statistically significant increase was demonstrated with voxelotor at both the 1,500-mg and 900-mg doses after 12 weeks of treatment versus placebo,” Global Blood Therapeutics said in an August regulatory filing with the Securities and Exchange Commission.

The company has said that voxelotor may meet the FDA’s standard for accelerated approval under Subpart H program.

In his presentation at the NIH conference, Tom Williams, MD, PhD, of KEMRI/Wellcome Trust Research Programme highlighted a recent review of experimental SCD treatments by Marilyn Jo Telen, MD, of Duke University, Durham, N.C. (Blood. 2016;127[7]:810-9).

Also among the drugs being tested for SCD is Modus Therapeutics’ sevuparin, which Dr. Williams described as being “a heparin-like molecule without the anticoagulant complications.”

The compound originated as a “passion project” of Mats Wahlgren, MD, PhD, of the Karolinska Institute, Stockholm, who developed it for the treatment of malaria, Dr. Williams said. The company that’s developing sevuparin, Modus Therapeutics, is moving it forward first as a treatment for SCD for commercial reasons, Dr. Williams said.

“They think it’s a better first target,” he said.

An ongoing study of sevuparin for painful crisis is expected to be completed in December, with data then expected to be released in the middle of 2019, Ellen K. Donnelly, PhD, chief executive officer of Modus Therapeutics, said in an interview. She cited a mix of scientific, medical and commercial reasons for her company’s decision to advance sevuparin in SCD.

“First, and most importantly, there is proof of clinical benefit of a similar molecule (the low-molecular-weight heparin called tinzaparin) in patients with sickle cell disease,” Dr. Donnelly said. “Unfortunately, there is a bleeding risk with tinzaparin that limits use of the agent for the treatment of sickle cell disease. Sevuparin does not have the bleeding risk and thus is a strong candidate for SCD.”

Dr. Donnelly also noted the emphasis that the FDA’s Division of Hematology Products has put on development of therapeutics for SCD as a reason for proceeding first with this indication. The agency and the American Society of Hematology in early October held a workshop of experts, physicians, patients, and industry collaborators focused on identifying new endpoints for clinical studies.

Still, she noted that commercial reasons did factor into this decision.

“[I]t is possible for a small company like Modus to take an asset all the way to market when developing a therapeutic for a rare disease given the need for fewer patients and smaller trials,” Dr. Donnelly wrote. “As you can see from www.clinicaltrials.gov, we were able to run our phase 2 study with a small number of sites. In addition, in SCD it is possible to get approval with only one or two confirmatory studies.”
 

Financial interests

Other drugs in testing for SCD include rivipansel from GlycoMimetics, for which Pfizer is leading development. The sponsors expect to complete the so-called RESET trial by 2019, according to the clinicaltrials.gov. In this study, which is intended to enroll 350 participants, patients who have vaso-occlusive crises are randomly selected for treatment with either rivipansel or placebo.

Speaking during a question-and-answer session at the NIH conference, Robert Swift, PhD, said there’s a need for inexpensive oral drugs to treat SCD. Many other options will remain beyond the finances of people living in poor countries, he said.

“We need to focus not only on the root cause, but on something that is oral and inexpensive to solve the greater sickle cell problem,” Dr. Swift said.

Large drugmakers already have hospital-based sales forces, making SCD drugs administered in this setting attractive to them, he said.

“This is partly about where money is. The drug companies are going where the money is. It’s not oral drugs to treat everybody, it’s something else,” Dr. Swift said. “So someone else is going to have to fund the basic research” into treatments that could be more broadly used.

Dr. Swift said in an interview that he has received NIH funding for developing SCD-101, an oral drug, for which a placebo-controlled crossover study is underway.

Presenters at the NIH conference, including Dr. Saunthararajah, expressed frustration about what they see as relatively little work being done on SCD despite decades of knowledge about the root causes. Like Dr. Swift, he criticized the approach taken in selecting which treatments advance in this field.

“It’s not being driven by what is the most cost effective, what the patients need the most,” Dr. Saunthararajah said. “It’s driven by what will make the most money, not just for [the] drug company, but also for the hospital and also for the physicians.”

Dr. Saunthararajah reported having patents and patent applications around decitabine/tetrahydrouridine, 5-azacytidine/tetrahydrouridine, and differentiation therapy for oncology. He has also been a consultant for EpiDestiny, Novo Nordisk, and Takeda Oncology. Dr. Williams reported having no relevant financial disclosures. Dr. Swift is a managing member of Invenux and reported equity in Mast Therapeutics and SCD Development.

This article was updated on 11/9/2018.

BETHESDA, MD. – Obtaining an extended red cell antigen profile before a patient’s first transfusion can help improve outcomes and avoid complications in highly transfused patients, according to one researcher.

“We strongly feel that you should get an extended red cell type on the first encounter” for patients facing long-term transfusion support, Connie Westhoff, PhD, of the New York Blood Center, said at Sickle Cell in Focus, a conference held by the National Institutes of Health. “This can be a one-time test. It doesn’t have to be repeated.”

She also stressed the importance of ensuring that this information travels with patients, who may be seen at various hospitals. “One of the challenges here is making this part of the patient’s electronic medical record.”

Alloimmunization has been a major concern for chronically transfused patients, so there’s a real advantage to knowing a patient’s extended red cell antigen profile before the patient develops alloantibodies following transfusion, Dr. Westhoff said. Hemolytic transfusion reactions can sometimes destroy patients’ own RBCs in addition to the transfused RBCs. Having the patient’s profile to identify the potential cause of the incompatibility and guide transfusion support in an emergency can be lifesaving.

The implementation of genotyping by DNA-based methods has brought down the cost of this screening, making it no longer a barrier in care.


Dr. Westhoff cited a study she and her colleagues published on a study typing patients who have sickle cell disease (Transfusion. 2015 Jun;55[6 Pt 2]:1388-93). In that paper, they found that DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens, compared with hemagglutination methods. This led to its implementation as the primary method for extended RBC typing for patients with sickle cell disease at the Children’s Hospital of Philadelphia.

About 65%-70% of antibodies drop to levels that are not detectable by routine assays, further demonstrating the need for DNA-based methods. The drugs used to dampen the immune response in many of these patients may also hinder or impact detection of antibodies that remain at levels that continue to cause in vivo hemolysis, Dr. Westhoff said in an interview.

For patients with sickle cell disease in many Western countries, antigen matching for CEK, at a minimum, is routine. The United States is now moving in this direction.

“Modern transfusion practice is moving to knowing what antigens the patient is at risk to become immunized against. ... What antigens does the patient lack and what antibodies could the patient make,” Dr. Westhoff said in an interview. “It’s a major advantage in your transfusion service to expedite work-ups and patient care by having that extended antigen profile.”

Dr. Westhoff reported no relevant financial disclosures.

BETHESDA, MD. – Obtaining an extended red cell antigen profile before a patient’s first transfusion can help improve outcomes and avoid complications in highly transfused patients, according to one researcher.

“We strongly feel that you should get an extended red cell type on the first encounter” for patients facing long-term transfusion support, Connie Westhoff, PhD, of the New York Blood Center, said at Sickle Cell in Focus, a conference held by the National Institutes of Health. “This can be a one-time test. It doesn’t have to be repeated.”

She also stressed the importance of ensuring that this information travels with patients, who may be seen at various hospitals. “One of the challenges here is making this part of the patient’s electronic medical record.”

Alloimmunization has been a major concern for chronically transfused patients, so there’s a real advantage to knowing a patient’s extended red cell antigen profile before the patient develops alloantibodies following transfusion, Dr. Westhoff said. Hemolytic transfusion reactions can sometimes destroy patients’ own RBCs in addition to the transfused RBCs. Having the patient’s profile to identify the potential cause of the incompatibility and guide transfusion support in an emergency can be lifesaving.

The implementation of genotyping by DNA-based methods has brought down the cost of this screening, making it no longer a barrier in care.


Dr. Westhoff cited a study she and her colleagues published on a study typing patients who have sickle cell disease (Transfusion. 2015 Jun;55[6 Pt 2]:1388-93). In that paper, they found that DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens, compared with hemagglutination methods. This led to its implementation as the primary method for extended RBC typing for patients with sickle cell disease at the Children’s Hospital of Philadelphia.

About 65%-70% of antibodies drop to levels that are not detectable by routine assays, further demonstrating the need for DNA-based methods. The drugs used to dampen the immune response in many of these patients may also hinder or impact detection of antibodies that remain at levels that continue to cause in vivo hemolysis, Dr. Westhoff said in an interview.

For patients with sickle cell disease in many Western countries, antigen matching for CEK, at a minimum, is routine. The United States is now moving in this direction.

“Modern transfusion practice is moving to knowing what antigens the patient is at risk to become immunized against. ... What antigens does the patient lack and what antibodies could the patient make,” Dr. Westhoff said in an interview. “It’s a major advantage in your transfusion service to expedite work-ups and patient care by having that extended antigen profile.”

Dr. Westhoff reported no relevant financial disclosures.

BETHESDA, MD. – Obtaining an extended red cell antigen profile before a patient’s first transfusion can help improve outcomes and avoid complications in highly transfused patients, according to one researcher.

“We strongly feel that you should get an extended red cell type on the first encounter” for patients facing long-term transfusion support, Connie Westhoff, PhD, of the New York Blood Center, said at Sickle Cell in Focus, a conference held by the National Institutes of Health. “This can be a one-time test. It doesn’t have to be repeated.”

She also stressed the importance of ensuring that this information travels with patients, who may be seen at various hospitals. “One of the challenges here is making this part of the patient’s electronic medical record.”

Alloimmunization has been a major concern for chronically transfused patients, so there’s a real advantage to knowing a patient’s extended red cell antigen profile before the patient develops alloantibodies following transfusion, Dr. Westhoff said. Hemolytic transfusion reactions can sometimes destroy patients’ own RBCs in addition to the transfused RBCs. Having the patient’s profile to identify the potential cause of the incompatibility and guide transfusion support in an emergency can be lifesaving.

The implementation of genotyping by DNA-based methods has brought down the cost of this screening, making it no longer a barrier in care.


Dr. Westhoff cited a study she and her colleagues published on a study typing patients who have sickle cell disease (Transfusion. 2015 Jun;55[6 Pt 2]:1388-93). In that paper, they found that DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens, compared with hemagglutination methods. This led to its implementation as the primary method for extended RBC typing for patients with sickle cell disease at the Children’s Hospital of Philadelphia.

About 65%-70% of antibodies drop to levels that are not detectable by routine assays, further demonstrating the need for DNA-based methods. The drugs used to dampen the immune response in many of these patients may also hinder or impact detection of antibodies that remain at levels that continue to cause in vivo hemolysis, Dr. Westhoff said in an interview.

For patients with sickle cell disease in many Western countries, antigen matching for CEK, at a minimum, is routine. The United States is now moving in this direction.

“Modern transfusion practice is moving to knowing what antigens the patient is at risk to become immunized against. ... What antigens does the patient lack and what antibodies could the patient make,” Dr. Westhoff said in an interview. “It’s a major advantage in your transfusion service to expedite work-ups and patient care by having that extended antigen profile.”

Dr. Westhoff reported no relevant financial disclosures.