Feature

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In the United States, cryoablation or freezing tissue to death is a primary treatment option for a variety of cancers, including those originating in or spread to the bone, cervix, eye, kidney, liver, lung, pancreas, prostate, and skin.

Cryoablation for prostate cancer, one of the most common cancers in men, was first approved in the 1990s.

But unlike in Europe, this nonsurgical approach is not approved for breast cancer in the United States; it is one of the most common cancers in women.

So why is this approach still experimental for breast cancer?

“I don’t know,” answered cryoablation researcher Richard Fine, MD, of West Cancer Center in Germantown, Tenn., when asked by this news organization.

“It’s very interesting how slow the [Food and Drug Administration] is in approving devices for breast cancer [when compared with] other cancers,” he said.
 

New clinical data

Perhaps new clinical data will eventually lead to approval of this nonsurgical technique for use in low-risk breast cancer. However, the related trial had a controversial design that might discourage uptake by practitioners if it is approved, said an expert not involved in the study.

Nevertheless, the new data show that cryoablation can be an effective treatment for small, low-risk, early-stage breast cancers in older patients.

The findings come from ICE-3, a multicenter single-arm study of cryoablation in 194 such patients with mean follow-up of roughly 3 years.

It used liquid nitrogen-based cryoablation technology from IceCure Medical Ltd., an Israeli company and the study sponsor.

The results show that 2.06% (n = 4) of patients had a recurrence in the same breast, which is “basically the same” as lumpectomy, the surgical standard for this patient group, said Dr. Fine, the lead investigator on the trial.

These are interim data, Dr. Fine said at the American Society of Breast Surgeons annual meeting, held virtually.

The primary outcome is the 5-year recurrence rate, and this is the first-ever cryoablation trial that does not involve follow-up surgery, he said.

Cryoablation, which delivers a gas to a tumor via a thin needle-like probe that is guided by ultrasound, has multiple advantages over surgery, Dr. Fine said.

“The noninvasive procedure is fast, painless, and can be delivered under local anesthesia in a doctor’s office. Recovery time is minimal and cosmetic outcomes are excellent with little loss of breast tissue and no scarring,” he said in a meeting press statement.

The potential market for cryoablation in breast cancer is large, as it is intended for tumors ≤1.5 cm, which comprise approximately 60%-70% of stage 1 breast cancers that are hormone receptor–positive (HR+), and HER2-negative (HER2–), Dr. Fine said in an interview.

Cryoablation is part of a logical, de-escalation of breast cancer care, he added. “We have moved from radical mastectomy to modified mastectomy to lumpectomy – so the next step in that evolution is ablative technology, which is ‘nonsurgical.’ ”

There are other experimental ablative treatments for breast cancer including high-frequency ultrasound and laser, but cryoablation is the furthest along in development.

Cryoablation as a primary cancer treatment was first approved for coverage by the Centers for Medicare & Medicaid Services for localized prostate cancer in 1999.

But the concept extends back to 1845, when English physician James Arnott first used iced salt solutions (about –20 °C or – 4 °F) to induce tissue necrosis, reducing tumor size and ameliorating pain. Because the crude cryogen needed to be applied topically, the pioneering technique was limited to breast and cervical cancers because of their accessibility.
 

Not likely to show superiority

The new study’s population was composed of women aged 60 years or older (mean of 75 years) with unifocal invasive ductal cancers measuring ≤1.5 cm or less that were all low-grade, HR+, and HER2–, as noted.

The liquid nitrogen–based cryoablation consisted of a freeze-thaw-freeze cycle that totals 20-40 minutes, with freezing temperatures targeting the tumor area and turning it into an “ice ball.”

That ice ball eventually surrounds the tumor, creating a “lethal zone,” and thus a margin in which no cancer exists, akin to surgery, said Dr. Fine.

There were no significant device-related adverse events or complications reported, say the investigators. Most of the adverse events were minor and included bruising, localized edema, minor skin freeze burn, rash, minor bleeding from needle insertion, minor local hematoma, skin induration, minor infection, and pruritis.

Two of 15 patients who underwent sentinel lymph node biopsies had a positive sentinel node. At the discretion of their treating physician, 27 patients underwent adjuvant radiation, 1 patient received chemotherapy, and 148 began endocrine therapy. More than 95% of the patients and 98% of physicians reported satisfaction from the cosmetic results during follow-up visits.

Because not all patients underwent sentinel lymph node biopsy and adjuvant radiation, there is likely to be controversy about this approach, suggested Deanna J. Attai, MD, a breast surgeon at the University of California, Los Angeles, and past president of the American Society of Breast Surgeons, who was asked for comment.

“We have studies that [indicate that] these treatments don’t add significant benefit [in this patient population] but there still is this hesitation [to forgo them],” she told this news organization.

“The patients in this study were exceedingly low risk,” she emphasized.

“Is 5 years enough to assess recurrence rates? The answer is probably no. Recurrences or distant metastases are more likely to happen 10-20 years later.”

Thus, it will be difficult to show that cryoablation is superior to surgery, she said.

“You can show that cryoablation is not inferior to lumpectomy alone – which allows patients to avoid the operating room,” Dr. Attai summarized.
 

The surgical mindset and breast cancer

Dr. Attai, who was not involved in the current trial, was an investigator in an earlier single-arm cooperative group study of cryoablation for breast cancer, which had the rate of complete tumor ablation as the primary outcome. The study, known as the American College of Surgeons Oncology Group Z1072 trial, enrolled 99 patients, all of whom underwent ablation followed by surgery. The study reported results in 2014 but was very slow to develop, she observed.

“I did my first training in 2004 and I don’t think the study opened for several years after that. I think there’s been a lot of hesitation to change the mindset that every cancer needs to be removed surgically,” Dr. Attai stated.

“When you put breast cancer in the context of the other organs, we are lagging behind a bit [with cryoablation],” she added.

“I don’t want to go there but … the innovation for male diseases and procedures sometimes surpasses that of women’s diseases,” she said.

But she also defended her fellow practitioners. “There’s been tremendous changes in management over the 27 years I’ve been in practice,” she said, citing the movement from mastectomy to lumpectomy as one of multiple big changes.

The disparity between the development of cryoablation for breast and prostate cancer is a mystery when you contemplate the potential side effects, Dr. Fine observed. “There’s not a lot of vital structures inside the breast, so you don’t have risks that you have with the prostate, including urinary incontinence and impotence.”

As a next move, the American Society of Breast Surgeons is planning to establish a cryoablation registry and aims to enroll 50 sites and 500 patients who are aged 55-85 years; for those aged 65-70, radiation therapy will be required, said Dr. Fine.

Currently, cryoablation for breast cancer is allowed only in a clinical trial, so a registry would expand usage considerably, he said.

However, cryoablation, including from IceCure, has FDA clearance for ablating cancerous tissue in general (but not breast cancer specifically).  

Dr. Attai hopes the field is ready for the nonsurgical approach.

“Halsted died in 1922 and the Halsted radical mastectomy really didn’t start to fall out of favor until the 1950s, 1960,” said Dr. Attai, referring to Dr William Halsted, who pioneered the procedure in the 1890s. “I would hope we are better at speeding up our progress. Changing the surgical mindset takes time,” she said.

Dr. Fine was an investigator in the ICE3 trial, which is funded by IceCure Medical. Dr. Attai has disclosed no relevant financial relationships.

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

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

In early June the Food and Drug Administration – amid a storm of controversy – approved aducanumab, a monoclonal antibody developed to treat Alzheimer’s disease. The approval was hailed by advocacy groups and some practitioners as a victory for patients and families, as the drug – the first anti-Alzheimer’s agent to reach the market in 18 years – is a potentially disease-modifying therapy, which acts to clear amyloid plaques from the brain.

But several prominent Alzheimer’s researchers lambasted the agency’s decision, citing unclear evidence of benefit, trials that did not meet their primary endpoints, and reliance on a post hoc analysis of a high-dose subgroup of patients in a halted trial to argue that aducanumab (Aduhelm, Biogen, and Eisai), slowed cognitive and functional decline by 22% on one measure. In November 2020, 10 of 11 members of an independent FDA advisory committee voted against aducanumab’s approval, citing holes in the data and concerns about the quality of the evidence. After the agency went on to approve anyway, three members of that committee resigned in protest.

The FDA decision on aducanumab was made using the agency’s accelerated approval pathway, which allows for the use of a surrogate endpoint – in this case imaging that showed amyloid clearance from the brain – to predict clinical benefit. But amyloid clearance, which a number of experimental antiamyloid antibodies have been shown capable of, has not been definitively linked to clinical benefit. Aducanumab, which is delivered by monthly intravenous infusion, will be marketed pending results from a phase 4 clinical trial, which the manufacturer has nearly a decade to complete. The drug’s price was announced at $56,000 per year, underscoring concern over its modest-at-best benefits.

Clinicians prescribing aducanumab must obtain magnetic resonance imaging at baseline and repeatedly during the course of treatment to detect brain edema and microhemorrhages, which occurred in a third of high-dose patients in clinical trials. Beyond this, there are few restrictions. The FDA label allows for its use in any patient deemed to have Alzheimer’s disease, without stipulations as to disease stage or evidence of brain amyloid. Payers, of course, are likely to restrict use to certain patient groups, and to require evidence of amyloid positivity. The FDA offered no guidance on when treatment should be ceased, leaving payers to make that call as well. Whatever aducanumab’s value and role turns out to be, the first-in-class treatment for Alzheimer’s disease is likely to have a major impact on how patients are assessed and treated in the coming years, and embolden manufactures of similar agents to seek FDA approval.

This news organization reached out to researchers, advocates, and specialists in the community to learn how they see this change playing out.
 

Fielding broad interest

Maria C. Carrillo, PhD, chief science officer of the Alzheimer’s Association, which was a strong proponent of aducanumab’s approval, acknowledged in an interview that the months to come are likely to be confusing for practitioners and families alike as the drug makes its way into community practices.

“We understand that off the bat millions of Americans will not have access to this tomorrow, but over time that will build. And the physician community, the specialists most likely to be prescribing this, over the next few years will even expand further,” Dr. Carrillo said.

For now, those specialists are mostly just struggling to respond responsibly to a deluge of inquiries from patients and their families.

“I’ve gotten like 20 calls in the just the past 2 days,” said neurologist Philip R. Delio, MD, who practices in Santa Barbara, Calif. “This is a longstanding issue that physicians have with patients’ access to information. Patients are getting information about a drug which isn’t available yet. They don’t know that it’s not ready to be sold. They don’t necessarily realize that a biopharma company won’t go into production until the FDA approves the drug.”

The challenge of delivery

Intravenous infusions are new to Alzheimer’s disease and pose all sorts of logistical hurdles. The Alzheimer’s Association’s Dr. Carrillo described the situation as “manageable,” noting that infusions are standard of care for many diseases, and that neurologists now have more than 15 years’ experience with them for multiple sclerosis.

Still, most clinicians treating Alzheimer’s disease in the community – neurologists, geriatricians, psychiatrists, and primary care physicians – do not have infusion centers in their practices. Virtually none have experience with or access to PET-amyloid, or with screening for amyloid-related imaging abnormalities–edema (ARIA-e) on MRI, as required by the FDA.

“I contacted the hospital infusion center we use and said I could end up sending five or six patients a week, can you handle this? They only have so many chairs,” Dr. Delio said. “I am one neurologist in a local community, and I might have 50 candidates for this drug. That’s a lot for them.” Patients with cognitive impairment are also difficult to infuse and may need to be treated at home, he noted.

“MRIs are easy enough to do,” Dr. Delio said. “But do we know what ARIA-e looks like on imaging? You’d have to talk to the radiologists – this is another element of uncertainty. Do we even know what we’re looking for with these scans? Will we recognize this?”

Neurologist Jeffrey L. Cummings, MD, ScD, of the University of Nevada, Las Vegas, a vocal proponent of aducanumab and lead author of a May 2021 paper defending the evidence for it, acknowledged that the field was unprepared for a wide-scale adoption of infusions in dementia treatment, pointing to a Rand Corporation study from 2017 that warned that screening, diagnosis, and availability of infusion chairs would have to be drastically scaled up to meet demand.

“There are few clinicians who know how to identify MCI, too few imaging centers, too few radiologists who know how to identify ARIA-e on MRI, so all of these things will be required to be put into place. The label doesn’t specify any of this, but good clinical practice will require that, and getting this up and running will take 18 to 24 months,” Dr. Cummings said.

Neurologist David S. Knopman, MD, of the Mayo Clinic in Rochester, Minn., a leading critic of the evidence for aducanumab who recently resigned his position on the independent committee that advises the FDA on neurology drugs, said that for large research institutions like his that have served as trial sites, the transition to offering PET-amyloid, MRI, and infusions in clinical practice will be easier.

Uncertainty over costs

Aducanumab’s true costs, to patients and to taxpayers, remain unknown. The $56,000 per year currently cited by its manufacturer “doesn’t count the PET scans and MRIs,” Dr. Knopman noted. “We’re probably pushing $100,00 a year for the first year of treatment.”

Most of that expense will likely be borne by Medicare, he said, and if not, “that will exacerbate existing health care disparities. People who can pay out of pocket are a pretty limited group.”

Dr. Scharre agreed that the costs of treatment were concerning, and that “at least you should be able to narrow it down and hopefully just use health care dollars for people who might stand to benefit,” he said – namely patients in an earlier stage of disease.

The Alzheimer’s Association’s Dr. Carrillo declined to address the high price of aducanumab or its implications, saying only that the association is “very invested in all aspects of access including covering costs associated with the drug and the rest of treatment.”

Access also means “infrastructure, access to physicians to diagnose, access to diagnostics,” Dr. Carrillo said.

Dr. Cummings said aducanumab’s price would likely come down through negotiations with the Centers for Medicare & Medicaid Services, copayments, and bulk purchases.

The FDA has offered no guidance on how long treatment with aducanumab should last, or what should prompt withdrawal of treatment, meaning that patients could, in theory, stay on it to the end of their lives – raising costs further.

Critics have also noted that a built-in financial incentive under Medicare Part B, which covers infusion drugs, could result in overprescription of aducanumab. Under Medicare Part B, prescribing physicians are reimbursed 6% of a drug’s average sales price.
 

Geriatricians wary

On social media and in the lay press, geriatricians have been among the most outspoken opponents of the FDA decision and the Alzheimer’s Association’s advocacy of aducanumab.

Eric Widera, MD, a geriatrician at the University of California, San Francisco, said that the specialty might be less likely than others to embrace aducanumab. “I think part of the reasons geriatricians don’t make a lot of money is they have strong commitment to their values,” Dr. Widera said.

A fractured research community

Ever since October 2019, when Biogen and Eisai announced that despite two trials halted for futility, they would go ahead and seek FDA approval for aducanumab, the Alzheimer’s research community has been bitterly divided over the drug and the FDA’s accelerated approval process.

Top researchers published critical editorials in journals, with some eventually taking their case to major newspapers as well. The Alzheimer’s Association’s position on the drug has clashed with that of many researchers whose work it supports.

“The Alzheimer’s community has been wonderfully collegial – we all have a common purpose,” Dr. Cummings said. “Now we have people taking extreme positions and I’m hoping this will not result in a permanent fracturing of the community.”

Chief among the critics’ concerns is that the FDA decision ratified the use of antiamyloid therapies based on biomarker evidence, opening the door for makers of similar drugs – those still under development or even those whose development has been halted – to seek approval on weak evidence of clinical benefit.

Whether the approval will chill research into drugs targeting pathways other than amyloid is uncertain.

Dr. Cummings said he felt that while the aducanumab decision would spur other manufacturers of antiamyloid drugs to seek accelerated approval, other classes of Alzheimer’s therapies in development also stand to get a boost. Many Alzheimer’s experts believe that a combination of drugs targeting different elements of the disease pathway – not just amyloid – will be needed in the long run.

Dr. Scharre said that the buzz over aducanumab’s approval will have at least one concrete benefit: people getting into doctors’ offices sooner.

“The people who come into our memory centers represent only a fraction of people walking around with MCI – there are people out there who may have heard that it’s normal aging; they have decreased insight; there’s denial, there’s embarrassment – there’s hundreds of reasons people avoid getting seen,” he said.

“Perhaps they come in and learn that they don’t have any degenerative process but their thyroid is out of whack, or there’s something else causing cognitive impairment. And if they do have a degenerative process, they’ll have time to start [aducanumab], and hopefully get to see a reduction in the decline.”

Dr. Knopman was a site investigator for the Biogen aducanumab trials and has consulted for Samus Therapeutics, Third Rock, Roche, and Alzeca Biosciences. A former member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee, he was recused from the Nov. 6, 2020, meeting that voted against aducanumab. Dr. Cummings has consulted for Biogen, Eisai, and other manufacturers. Dr. Scharre reports financial relationships with Biogen, Brain Test, Acadia, and Vascular Scientific. Dr. Widera has no disclosures. Dr. Delio is a speaker for Gore Medical, Allergan, and Biohaven Pharmaceuticals.

Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of children with COVID-19 was 4,008,572 as of June 10 after just under 14,500 new cases were reported over the preceding week. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.

Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.

In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.

Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.

For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.

Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.

rfranki@mdedge.com

Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of children with COVID-19 was 4,008,572 as of June 10 after just under 14,500 new cases were reported over the preceding week. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.

Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.

In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.

Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.

For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.

Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.

rfranki@mdedge.com

Even as the number of new COVID-19 cases continues to drop, the United States reached the 4-million mark for infected children, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of children with COVID-19 was 4,008,572 as of June 10 after just under 14,500 new cases were reported over the preceding week. That weekly total, the lowest since June of 2020, comes from 49 states (excluding N.Y.), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

Children represent 14.1% of all COVID-19 cases since the beginning of the pandemic, while the corresponding figure for the week ending June 10 was 19.0%. That weekly proportion of cases among children had been rising pretty steadily through the winter and early spring, but the situation has become much more volatile over the last month, the AAP/CHA data show.

Use of the Pfizer-BioNTech vaccine in children aged 16-17 years, of course, didn’t begin until April, and the vaccine wasn’t authorized for children aged 12-15 years until mid-May. The Moderna and Johnson & Johnson vaccines have not received such authorization yet, but Moderna is in the process of seeking an emergency-use recommendation from the Food and Drug Administration.

In the younger group of children who are currently eligible, completion of the vaccine regimen took a big jump in the week ending June 14, according to the Centers for Disease Control and Prevention. The cumulative share of those aged 12-15 years who had received a second dose jumped from 4.1% on June 7 to 11.4% on June 14, with comparable numbers for 16- and 17-year-olds coming in at 26.4% and 29.1%.

Activity over just the last 14 days, however, shows a slight decrease in children aged 12-15 getting a first dose: For just the 2 weeks ending June 7, 17.9% of all children in the age group initiated a first dose, but for the 14 days ending June 14, only 17.1% of the age group did so, the CDC said on its COVID Data Tracker site.

For children aged 16-17 years – of whom less than 30% have reached full vaccination – activity seems to have stagnated: 4.8% of all 16- to 17-year-olds initiated a first vaccination during the 14 days ending June 7, compared with 4.7% who did so during the 14 days ending June 14, the CDC reported.

Older age groups with higher completion rates are still producing greater vaccine initiation. As of June 14, those aged 25-39 years had a completion rate of 41.9% and 24.0% of the age group had received a first dose in the previous 2 weeks, while 61.4% of those aged 50-64 were fully vaccinated, and 18.0% had gotten their first dose, the CDC data indicate.

rfranki@mdedge.com

For physicians who are just starting out or thinking about moving, the “Land of 10,000 Lakes” could be the land of opportunity, according to a recent Medscape analysis.

In a ranking of the 50 states, Minnesota “claimed top marks for livability, low incidence of adverse actions against doctors, and the performance of its health system,” Shelly Reese wrote in Medscape’s “Best & Worst Places to Practice 2021.”

Minnesota is below average where it’s good to be below average – share of physicians reporting burnout and/or depression – but above average in the share of physicians who say they’re “very happy” outside of work, Medscape said in the annual report.

Second on this year’s list is Wisconsin, which benefits from low levels of malpractice payouts and adverse actions and a high level of livability. Third place went to Washington (called the most livable state in the country by U.S. News and World Report), fourth to Colorado (physicians happy at and outside of work, high retention rate for residents), and fifth to Utah (low crime rate, high quality of life), Medscape said.

At the bottom of the list for 2021 is West Virginia, where physicians “may confront a bevy of challenges” in the form of low livability, a high rate of adverse actions, and relatively high malpractice payouts, Ms. Reese noted in the report.

State number 49 is Louisiana, where livability is low, malpractice payouts are high, and more than half of physicians say that they’re burned out and/or depressed. New Mexico is 48th (very high rate of adverse actions, poor resident retention), Nevada is 47th (low marks for avoidable hospital use and disparity in care), and Rhode Island is 46th (high malpractice payouts, low physician compensation), Medscape said.

Continuing with the group-of-five theme, America’s three most populous states finished in the top half of the ranking – California 16th, Texas 11th, and Florida 21st – but New York and Pennsylvania, numbers four and five by population size, did not.

The rankings are based on states’ performance in 10 different measures, three of which were sourced from Medscape surveys – happiness at work, happiness outside of work, and burnout/depression – and seven from other organizations: adverse actions against physicians, malpractice payouts, compensation (adjusted for cost of living), overall health, health system performance, overall livability, resident retention.
 

rfranki@mdedge.com

For physicians who are just starting out or thinking about moving, the “Land of 10,000 Lakes” could be the land of opportunity, according to a recent Medscape analysis.

In a ranking of the 50 states, Minnesota “claimed top marks for livability, low incidence of adverse actions against doctors, and the performance of its health system,” Shelly Reese wrote in Medscape’s “Best & Worst Places to Practice 2021.”

Minnesota is below average where it’s good to be below average – share of physicians reporting burnout and/or depression – but above average in the share of physicians who say they’re “very happy” outside of work, Medscape said in the annual report.

Second on this year’s list is Wisconsin, which benefits from low levels of malpractice payouts and adverse actions and a high level of livability. Third place went to Washington (called the most livable state in the country by U.S. News and World Report), fourth to Colorado (physicians happy at and outside of work, high retention rate for residents), and fifth to Utah (low crime rate, high quality of life), Medscape said.

At the bottom of the list for 2021 is West Virginia, where physicians “may confront a bevy of challenges” in the form of low livability, a high rate of adverse actions, and relatively high malpractice payouts, Ms. Reese noted in the report.

State number 49 is Louisiana, where livability is low, malpractice payouts are high, and more than half of physicians say that they’re burned out and/or depressed. New Mexico is 48th (very high rate of adverse actions, poor resident retention), Nevada is 47th (low marks for avoidable hospital use and disparity in care), and Rhode Island is 46th (high malpractice payouts, low physician compensation), Medscape said.

Continuing with the group-of-five theme, America’s three most populous states finished in the top half of the ranking – California 16th, Texas 11th, and Florida 21st – but New York and Pennsylvania, numbers four and five by population size, did not.

The rankings are based on states’ performance in 10 different measures, three of which were sourced from Medscape surveys – happiness at work, happiness outside of work, and burnout/depression – and seven from other organizations: adverse actions against physicians, malpractice payouts, compensation (adjusted for cost of living), overall health, health system performance, overall livability, resident retention.
 

rfranki@mdedge.com

For physicians who are just starting out or thinking about moving, the “Land of 10,000 Lakes” could be the land of opportunity, according to a recent Medscape analysis.

In a ranking of the 50 states, Minnesota “claimed top marks for livability, low incidence of adverse actions against doctors, and the performance of its health system,” Shelly Reese wrote in Medscape’s “Best & Worst Places to Practice 2021.”

Minnesota is below average where it’s good to be below average – share of physicians reporting burnout and/or depression – but above average in the share of physicians who say they’re “very happy” outside of work, Medscape said in the annual report.

Second on this year’s list is Wisconsin, which benefits from low levels of malpractice payouts and adverse actions and a high level of livability. Third place went to Washington (called the most livable state in the country by U.S. News and World Report), fourth to Colorado (physicians happy at and outside of work, high retention rate for residents), and fifth to Utah (low crime rate, high quality of life), Medscape said.

At the bottom of the list for 2021 is West Virginia, where physicians “may confront a bevy of challenges” in the form of low livability, a high rate of adverse actions, and relatively high malpractice payouts, Ms. Reese noted in the report.

State number 49 is Louisiana, where livability is low, malpractice payouts are high, and more than half of physicians say that they’re burned out and/or depressed. New Mexico is 48th (very high rate of adverse actions, poor resident retention), Nevada is 47th (low marks for avoidable hospital use and disparity in care), and Rhode Island is 46th (high malpractice payouts, low physician compensation), Medscape said.

Continuing with the group-of-five theme, America’s three most populous states finished in the top half of the ranking – California 16th, Texas 11th, and Florida 21st – but New York and Pennsylvania, numbers four and five by population size, did not.

The rankings are based on states’ performance in 10 different measures, three of which were sourced from Medscape surveys – happiness at work, happiness outside of work, and burnout/depression – and seven from other organizations: adverse actions against physicians, malpractice payouts, compensation (adjusted for cost of living), overall health, health system performance, overall livability, resident retention.
 

rfranki@mdedge.com

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A third dose of a COVID-19 vaccine can boost antibody levels in people who previously received a solid organ transplant and had an unsatisfactory response to their first two mRNA shots, according to data from a newly published 30-patient case series.

All of those with low titers before the third dose had high titers after receiving the additional shot, but only about 33% of those with negative initial responses had detectable antibodies after the third dose, according to the paper, published in Annals of Internal Medicine.

Researchers at Johns Hopkins, Baltimore, who keep a COVID-19 vaccine registry, perform antibody tests on all registry subjects and inform them of their results. Registry participants were asked to inform the research team if they received a third dose, and, the research team tracked the immune responses of those who did.

The participants in this case series had low antibody levels and received a third dose of the vaccine on their own between March 20 and May 10 of 2021.
 

Third dose results

In this cases series – thought to be the first to look at third vaccine shots in this type of patient group – all six of those who had low antibody titers before the third dose had high-positive titers after the third dose.

Of the 24 individuals who had negative antibody titers before the third dose, just 6 had high titers after the third dose.

Two of the participants had low-positive titers, and 16 were negative.

“Several of those boosted very nicely into ranges seen, using these assays, in healthy persons,” said William Werbel, MD, a fellow in infectious disease at Johns Hopkins Medicine, Baltimore, who helped lead the study. Those with negative levels, even if they responded, tended to have lower titers, he said.

“The benefits at least from an antibody perspective were not the same for everybody and so this is obviously something that needs to be considered when thinking about selecting patients” for a COVID-19 prevention strategy, he said.

Reactions to the vaccine were low to moderate, such as some arm pain and fatigue.

“Showing that something is safe in that special, vulnerable population is important,” Dr. Werbel said. “We’re all wanting to make sure that we’re doing no harm.”

Dr. Werbel noted that there was no pattern in the small series based on the organ transplanted or in the vaccines used. As their third shot, 15 of the patients received the Johnson & Johnson vaccine; 9 received Moderna; and 6 received Pfizer-BioNTech.
 

Welcome news, but larger studies needed

“To think that a third dose could confer protection for a significant number of people is of course extremely welcome news,” said Christian Larsen, MD, DPhil, professor of surgery in the transplantation division at Emory University, Atlanta, who was not involved in the study. “It’s the easiest conceivable next intervention.”

He added, “We just want studies to confirm that – larger studies.”

Dr. Werbel stressed the importance of looking at third doses in these patients in a more controlled fashion in a randomized trial, to more carefully monitor safety and how patients fare when starting with one type of vaccine and switching to another, for example.

Richard Wender, MD, chair of family medicine and community health at the University of Pennsylvania, Philadelphia, said the findings are a reminder that there is still a lot that is unknown about COVID-19 and vaccination.

“We still don’t know who will or will not benefit from a third dose,” he said. “And our knowledge is evolving.  For example, a recent study suggested that people with previous infection and who are vaccinated may have better and longer protection than people with vaccination alone. We’re still learning.”

He added that specialists, not primary care clinicians, should be relied upon to respond to this emerging vaccination data. Primary care doctors are very busy in other ways – such as in getting children caught up on vaccinations and helping adults return to managing their chronic diseases, Dr. Wender noted.

“Their focus needs to be on helping to overcome hesitancy, mistrust, lack of information, or antivaccination sentiment to help more people feel comfortable being vaccinated – this is a lot of work and needs constant focus. In short, primary care clinicians need to focus chiefly on the unvaccinated,” he said.

“Monitoring immunization recommendations for unique at-risk populations should be the chief responsibility of teams providing subspecialty care, [such as for] transplant patients, people with chronic kidney disease, cancer patients, and people with other chronic illnesses.  This will allow primary care clinicians to tackle their many complex jobs.”
 

Possible solutions for those with low antibody responses

Dr. Larsen said that those with ongoing low antibody responses might still have other immune responses, such as a T-cell response. Such patients also could consider changing their vaccine type, he said.

“At the more significant intervention level, there may be circumstances where one could change the immunosuppressive drugs in a controlled way that might allow a better response,” suggested Dr. Larsen. “That’s obviously going to be something that requires a lot more thought and careful study.”

Dr. Werbel said that other options might need to be considered for those having no response following a third dose. One possibility is trying a vaccine with an adjuvant, such as the Novavax version, which might be more widely available soon.

“If you’re given a third dose of a very immunogenic vaccine – something that should work – and you just have no antibody development, it seems relatively unlikely that doing the same thing again is going to help you from that perspective, and for all we know might expose you to more risk,” Dr. Werbel noted.
 

Participant details

None of the 30 patients were thought to have ever had COVID-19. On average, patients had received their transplant 4.5 years before their original vaccination. In 25 patients, maintenance immunosuppression included tacrolimus or cyclosporine along with mycophenolate. Corticosteroids were also used for 24 patients, sirolimus was used for one patient, and belatacept was used for another patient.

Fifty-seven percent of patients had received the Pfizer/BioNTech vaccine originally, and 43% the Moderna vaccine. Most of the patients were kidney recipients, with two heart, three liver, one lung, one pancreas and one kidney-pancreas.

Dr. Werbel, Dr. Wender, and Dr. Larsen reported no relevant disclosures.

A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.

In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.

“This is not coercion,” Judge Hughes wrote in the ruling.

“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”

In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.

“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”

He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.

“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”

Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.

“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”

The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”

The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.

Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.

“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”

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

A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.

In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.

“This is not coercion,” Judge Hughes wrote in the ruling.

“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”

In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.

“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”

He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.

“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”

Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.

“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”

The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”

The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.

Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.

“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”

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

A federal judge in Texas has dismissed a lawsuit from 117 Houston Methodist Hospital workers who refused to get a COVID-19 vaccine and said it was illegal to require them to do so.

In the ruling issued June 12, U.S. District Judge Lynn Hughes upheld the hospital’s policy and said the vaccination requirement didn’t break any federal laws.

“This is not coercion,” Judge Hughes wrote in the ruling.

“Methodist is trying to do their business of saving lives without giving them the COVID-19 virus,” he wrote. “It is a choice made to keep staff, patients, and their families safer.”

In April, the Houston Methodist Hospital system announced a policy that required employees to be vaccinated by June 7 or request an exemption. After the deadline, 178 of 26,000 employees refused to get inoculated and were placed on suspension without pay. The employees said the vaccine was unsafe and “experimental.” In his ruling, Judge Hughes said their claim was false and irrelevant.

“Texas law only protects employees from being terminated for refusing to commit an act carrying criminal penalties to the worker,” he wrote. “Receiving a COVID-19 vaccination is not an illegal act, and it carries no criminal penalties.”

He denounced the “press-release style of the complaint” and the comparison of the hospital’s vaccine policy to forced experimentation by the Nazis against Jewish people during the Holocaust.

“Equating the injection requirement to medical experimentation in concentration camps is reprehensible,” he wrote. “Nazi doctors conducted medical experiments on victims that caused pain, mutilation, permanent disability, and in many cases, death.”

Judge Hughes also said that employees can “freely choose” to accept or refuse a COVID-19 vaccine. If they refuse, they “simply need to work somewhere else,” he wrote.

“If a worker refuses an assignment, changed office, earlier start time, or other directive, he may be properly fired,” Judge Hughes said. “Every employment includes limits on the worker’s behavior in exchange for his remuneration. This is all part of the bargain.”

The ruling could set a precedent for similar COVID-19 vaccine lawsuits across the country, NPR reported. Houston Methodist was one of the first hospitals to require staff to be vaccinated. After the ruling on June 12, the hospital system wrote in a statement that it was “pleased and reassured” that Judge Hughes dismissed a “frivolous lawsuit.”

The hospital system will begin to terminate the 178 employees who were suspended if they don’t get a vaccine by June 21.

Jennifer Bridges, a nurse who has led the campaign against the vaccine policy, said she and the other plaintiffs will appeal the decision, according to KHOU.

“We’re OK with this decision. We are appealing. This will be taken all the way to the Supreme Court,” she told the news station. “This is far from over. This is literally only the beginning.”

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

In 2008, the U.S. Department of Labor (DOL) paid for Tony Adams, a 48-year-old coal miner, to have a chest x-ray. His doctor found stage I black lung disease. Yet Mr. Adams’ claim for medical benefits was denied. This was because the insurance group that represented his employer hired a different – more credentialed – doctor as its medical expert. That doctor said he saw no such evidence. The judge ruled in favor of the mining company on the basis of the latter’s “expertise.”

Before he died 5 years later, at age 53, Mr. Adams went through this process again. In fact, he did it four more times. Each time, his doctor found evidence of black lung, but the company’s medical expert did not. He died without receiving benefits. Among the causes of death listed on his autopsy were cardiopulmonary arrest and coal worker’s pneumoconiosis (CWP): black lung.

Since his death in 2013, two judges have awarded Mr. Adams’ benefits to his widow, Linda. Both times, the mining company appealed the decision, most recently in December 2020. She’s not giving up. “Two weeks before he died, he told me, ‘I’m going to die of black lung,’ ” Linda recalled. “‘But I don’t want you to give up on black lung. There are too many people screwing these miners out of what they deserve.’”

There has long been suspicion among miners and their advocates that doctors used by coal companies to fight claims like Mr. Adams’ are in the pocket of “Big Coal.” At the very least, some say these physicians are swayed by their client’s preference when reading a coal miner’s chest x-ray. A recent study published in Annals of the American Thoracic Society provides empirical evidence that these doctors’ conflict of interest – namely, that parties representing coal companies hired them – appears to influence their medical opinion.
 

Proof of a ‘broken system’

The Annals study examined 63,780 radiograph classifications made by 264 physicians – all certified as B-readers, a certification by the National Institute for Occupational Safety and Health (NIOSH) for physicians who demonstrate proficiency in classifying radiographs of pneumoconiosis. The results showed that doctors hired by miners identified black lung 49% of the time; those hired by coal companies identified black lung only 15% of the time.

The study also found that B-readers contracted by employers read results differently for different clients. The same doctors were significantly less likely to say a miner’s lungs were negative for CWP when they were hired by the DOL (77.2%) than when they were hired by a coal company or its insurers (90.2%).

The bias does appear to work both ways: B-readers hired by miners and miners’ attorneys were more likely to find evidence of black lung when they worked with plaintiffs. However, a much higher number of doctors appeared to be biased in favor of the companies. “There were 3X more B-readers providing 8X more classifications among those affiliated with employers compared to those affiliated with miners,” the study concluded.

The authors suggest that one reason for this was the difference in pay. Some company-hired doctors made as much as $750 per reading, about 10 times what miner-hired doctors were paid.

“We knew [about the potential bias] from our work over the decades taking care of these guys,” said Robert A. Cohen, MD, a pulmonologist and the study’s senior author. “But then you see it with P values that are incredibly statistically significant ...”

The study finally put numbers to a problem that many working with black lung claims had always assumed. Those within the system are accustomed to seeing names of the same doctors on documents and reports, with little to no overlap between those hired by the defense and the plaintiffs.

“The vast majority of the time, we know what a report will say based on the doctor’s name,” said Evan Smith, JD, advocacy director at AppalReD Legal Aid, in Prestonsburg, Ky.. It is far more surprising, he said, when a defense-hired doctor agrees with a miner-hired doctor.

Over the years, Katherine DePonte, MD, a radiologist and B-reader in West Virginia, has often seen an “almost textbook appearance” of CWP, only to later learn that “another radiologist read it as negative.” She explained, “They would use some other term, like ‘old granulomatous disease.’”

Employer-hired doctors often do acknowledge the same lung damage on the radiograph as miner-hired docs; they simply don’t attribute it to coal dust. Common “alternative diagnoses” include chronic obstructive pulmonary disease or histoplasmosis. “I know a number don’t believe this disease of coal worker pneumoconiosis exists [at all],” Dr. DePonte said.

What’s inarguable is that, even as coal mining in Appalachia is on the decline, black lung disease is on the rise. NIOSH now estimates that it affects over 20% of long-term (25+ years) coal workers in central Appalachia. That’s the highest prevalence in a quarter of a century.

Mr. Smith said that at its most basic level, these doctors’ conflicts of interest “lead to people who have the disease that these benefits are for, having them denied.” People like Tony Adams. Whether the doctors involved are complicit or just conservative, critics say they have become a fixture of a broken system.
 

Financial bias or difference of opinion?

Broken system or not, evidence suggests that the problem can’t be blamed solely on medical experts. Dr. DePonte primarily reads for the DOL and miners. “Not that I necessarily chose that,” she said. “You get pigeonholed.”

Some say that the bias demonstrated by the Annals study is at least partially driven by the litigation process itself. It is an adversarial system. As such, attorneys on both sides are naturally inclined to seek out doctors who will best support their clients’ cases. Doctors with a legitimately conservative perspective on what constitutes black lung are more sought after by the coal companies’ attorneys.

“It can often be impossible to tell whether the money is driving a change in the behavior or if the behavior is causing them to be sought out,” said Matt McCoy, PhD, a medical ethicist who specializes in conflicts of interest at the University of Pennsylvania, Philadelphia.

Although some believe that certain doctors are driven purely by financial incentive and offer a specific reading to secure repeat business, B-readers can end up working exclusively for companies because of other reasons. Wes Addington, JD, an attorney at the Appalachian Citizens’ Law Center, Whitesburg, Ky., said some doctors appear to have an authentically different – often antiquated – view of the disease.

Perhaps the most extreme example is Paul Wheeler, MD, a highly credentialed Johns Hopkins radiologist who was exposed for false medical testimony in Chris Hamby’s 2013 Pulitzer Prize reporting. In 1,500 readings, Dr. Wheeler never diagnosed a single case of severe black lung. And yet, Dr. Cohen, Mr. Addington, Mr. Smith, and other experts all agree that Dr. Wheeler appeared to wholeheartedly believe that his view of black lung was accurate. That made him a valuable asset to mining companies.

Since Dr. Wheeler’s exposure, there has been a greater sense of accountability among B-readers, said John Cline, JD, a West Virginia–based attorney who represents miners with federal black lung claims. “Radiologists were thinking, ‘Somebody could be watching me.’ Even if they thought they were doing this in the shadows, it made people more cautious,” he said.

The data used in the Annals study predate Mr. Hamby’s investigation, going back to 2000. Thus, it is possible that, as Mr. Cline argues, things may be different now. However, Lee S. Friedman, PhD, associate professor at the University of Illinois at Chicago, who is the lead author of the study, remains skeptical.

“While the Wheeler case might have dampened some physicians [who were] completely skewing their readings always negative, I think it’s premature or incorrect” to say it resolved the issue, he said. “Did they all change their behavior the morning after? It doesn’t seem likely, given the evidence of financial conflicts of interest and behavior that’s been demonstrated.”
 

Skewing the evidence?

Mr. Hamby’s 2013 reporting also revealed that even when company-hired doctors did diagnose CWP, law firms were burying those readings. In 2016, the DOL attempted to stop this practice. The agency made suppression of written evidence illegal – emphasis on written.

Law firms can’t hide positive reports, but they can prevent them. Dr. Cohen explained that now, “a doctor on the phone says, ‘I will read this as positive.’ Then the company says, ‘No, thank you,’ we will send you a check.”

This practice was confirmed by Kim Adcock, MD, a retired radiologist and B-reader in Littleton, Colo., who primarily reads for 26 law firms. Some of his clients want a report no matter how he reads the radiograph. However, some want him to call them first if he’s going to read the radiograph as positive. Dr. Adcock said this practice skews the dataset to make company-hired docs appear to read more negatively than they actually do.

Because the dataset used in the study is from the Federal Black Lung Program (FBLP), it includes only readings that made it to court. Dr. Adcock said he reads approximately 2,000 radiographs a year, although only a few of his readings appeared in the study’s dataset, according to a search by Dr. Friedman. This difference is likely because the study evaluated only readings between 2000 and 2013, the year Dr. Adcock started B-reading.

“I think it’s important to get a message that, to a certain extent, contravenes this paper. Yes, we should have some reservations about the conclusions,” Dr. Adcock explained. “There are people out there attempting to do the best job they could do.”

Law firms shopping for the reading they want and censoring the ones they don’t might alter the FBLP data, but experts say that doesn’t change the underlying problem. “In any case like this, where you’re looking at individuals going up against corporations,” Dr. McCoy said, “[corporations] are able to marshal their resources and hire more officials in a way claimants can’t, and that’s a baseline concern here.”
 

Battling bias

Admitting bias is notoriously difficult; thus, it isn’t surprising that many doctors involved refuse to believe they are influenced by money, incentives, or other biases. Dr. DePonte said she’s not swayed by money, nor does she actively take a pro-miner stance. She views herself as more of an advocate for accuracy. However, she did say that it has traditionally been far more difficult for miners to prove their cases, a problem that has improved with new regulations in recent years.

In Colorado, Dr. Adcock’s approach is to stay as far removed from the litigation process as possible. He said he has limited understanding of how his reports are used or how claims are filed and awarded. He leans heavily on his initial – almost instantaneous – impression of a chest x-ray.

Dr. DePonte and Dr. Adcock were both hired as experts on Tony Adams’ case. In 2008, Dr. DePonte read his chest x-ray as positive for early-stage black lung (1/0). Dr. Adcock also read two of Adams’ four chest x-rays, one in 2009 and the other in 2013. He read them as negative. When asked about the case, which autopsy confirmed as black lung, Dr. Adcock explained that positive histopathology doesn’t mean the radiograph reading was wrong, only that the disease didn’t show on that radiograph. He said his “highest ambition” is to be “an objective finder of fact” and that he trusts the process to work out the truth.

That process didn’t work in time for Tony Adams. Dr. Friedman argues that people who provide expert testimony have an ethical responsibility to know how their testimony is being used; to do otherwise, he says, is “willful ignorance.” Still, the Annals study authors, along with Dr. DePonte, Mr. Cline, and West Virginia attorney Sam Petsonk, say that the process is getting fairer, thanks to new policies developed over the past 5 years by the DOL.

“The DOL has worked very hard to reconcile the final award rate (around 30%) with the incidence of disease in the population (between 20% and 25%),” Mr. Petsonk said. Although the study calls into question the integrity of the system and the doctors within it, it’s critical for miners to know that the system is working and that they can get benefits, he explained. Many fear that cynicism about the system drives miners away and causes them to resort to Social Security or long-term disability.
 

Fixing what’s broken

The Annals study’s authors propose some solutions to the problems they quantified. The first is a sort of “super panel” that collectively evaluates readings. Although a completely unbiased panel would be nice, such impartiality is likely unsustainable, Mr. Smith said. He believes that over time, the panel would become vulnerable to politics and would work in favor of the companies.

Even without a panel, a method to provide greater transparency could be a great start, some suggest. The DOL could make the entire FBLP database public and analyze it annually. The authors also propose a flat fee for readings. Even now, Dr. Adcock said he doesn’t make anywhere close to the upper limit of $750 per readings. “My understanding is around $125 is a pretty characteristic fee [for reading a chest x-ray],” he elaborated. “Everyone I’ve had a conversation with is within 25 bucks [of that].”

That said, Dr. Adcock is not currently listed among the heavy readers who appear in the data used for the study; it’s possible that his experience is not representative. Some readers who were included in that dataset read more than 10 times the average number of classifications per reader – the average was 242 classifications – and read 95% of chest x-rays as negative, according to Dr. Friedman. This news organization obtained the names of two doctors whose readings were 95% negative on a high volume of cases. Neither agreed to an interview.

It’s possible that if the dataset had included readings from more recent years, Dr. Adcock would have appeared more frequently, given his personal estimates. That’s why the study authors recommend that the DOL conduct this kind of analysis annually in order to get an accurate picture of who is contributing to these cases, in what way, and how often. By doing so, readers who appear biased could be identified and addressed with more regularity, Dr. Friedman said.

Even if the rate were more consistent and the data were more frequently analyzed, the very nature of the adversarial system will put any potential solution at risk. “I’m not sure there’s a foolproof system that can be devised that can’t be corrupted in time,” Mr. Cline said.
 

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

In 2008, the U.S. Department of Labor (DOL) paid for Tony Adams, a 48-year-old coal miner, to have a chest x-ray. His doctor found stage I black lung disease. Yet Mr. Adams’ claim for medical benefits was denied. This was because the insurance group that represented his employer hired a different – more credentialed – doctor as its medical expert. That doctor said he saw no such evidence. The judge ruled in favor of the mining company on the basis of the latter’s “expertise.”

Before he died 5 years later, at age 53, Mr. Adams went through this process again. In fact, he did it four more times. Each time, his doctor found evidence of black lung, but the company’s medical expert did not. He died without receiving benefits. Among the causes of death listed on his autopsy were cardiopulmonary arrest and coal worker’s pneumoconiosis (CWP): black lung.

Since his death in 2013, two judges have awarded Mr. Adams’ benefits to his widow, Linda. Both times, the mining company appealed the decision, most recently in December 2020. She’s not giving up. “Two weeks before he died, he told me, ‘I’m going to die of black lung,’ ” Linda recalled. “‘But I don’t want you to give up on black lung. There are too many people screwing these miners out of what they deserve.’”

There has long been suspicion among miners and their advocates that doctors used by coal companies to fight claims like Mr. Adams’ are in the pocket of “Big Coal.” At the very least, some say these physicians are swayed by their client’s preference when reading a coal miner’s chest x-ray. A recent study published in Annals of the American Thoracic Society provides empirical evidence that these doctors’ conflict of interest – namely, that parties representing coal companies hired them – appears to influence their medical opinion.
 

Proof of a ‘broken system’

The Annals study examined 63,780 radiograph classifications made by 264 physicians – all certified as B-readers, a certification by the National Institute for Occupational Safety and Health (NIOSH) for physicians who demonstrate proficiency in classifying radiographs of pneumoconiosis. The results showed that doctors hired by miners identified black lung 49% of the time; those hired by coal companies identified black lung only 15% of the time.

The study also found that B-readers contracted by employers read results differently for different clients. The same doctors were significantly less likely to say a miner’s lungs were negative for CWP when they were hired by the DOL (77.2%) than when they were hired by a coal company or its insurers (90.2%).

The bias does appear to work both ways: B-readers hired by miners and miners’ attorneys were more likely to find evidence of black lung when they worked with plaintiffs. However, a much higher number of doctors appeared to be biased in favor of the companies. “There were 3X more B-readers providing 8X more classifications among those affiliated with employers compared to those affiliated with miners,” the study concluded.

The authors suggest that one reason for this was the difference in pay. Some company-hired doctors made as much as $750 per reading, about 10 times what miner-hired doctors were paid.

“We knew [about the potential bias] from our work over the decades taking care of these guys,” said Robert A. Cohen, MD, a pulmonologist and the study’s senior author. “But then you see it with P values that are incredibly statistically significant ...”

The study finally put numbers to a problem that many working with black lung claims had always assumed. Those within the system are accustomed to seeing names of the same doctors on documents and reports, with little to no overlap between those hired by the defense and the plaintiffs.

“The vast majority of the time, we know what a report will say based on the doctor’s name,” said Evan Smith, JD, advocacy director at AppalReD Legal Aid, in Prestonsburg, Ky.. It is far more surprising, he said, when a defense-hired doctor agrees with a miner-hired doctor.

Over the years, Katherine DePonte, MD, a radiologist and B-reader in West Virginia, has often seen an “almost textbook appearance” of CWP, only to later learn that “another radiologist read it as negative.” She explained, “They would use some other term, like ‘old granulomatous disease.’”

Employer-hired doctors often do acknowledge the same lung damage on the radiograph as miner-hired docs; they simply don’t attribute it to coal dust. Common “alternative diagnoses” include chronic obstructive pulmonary disease or histoplasmosis. “I know a number don’t believe this disease of coal worker pneumoconiosis exists [at all],” Dr. DePonte said.

What’s inarguable is that, even as coal mining in Appalachia is on the decline, black lung disease is on the rise. NIOSH now estimates that it affects over 20% of long-term (25+ years) coal workers in central Appalachia. That’s the highest prevalence in a quarter of a century.

Mr. Smith said that at its most basic level, these doctors’ conflicts of interest “lead to people who have the disease that these benefits are for, having them denied.” People like Tony Adams. Whether the doctors involved are complicit or just conservative, critics say they have become a fixture of a broken system.
 

Financial bias or difference of opinion?

Broken system or not, evidence suggests that the problem can’t be blamed solely on medical experts. Dr. DePonte primarily reads for the DOL and miners. “Not that I necessarily chose that,” she said. “You get pigeonholed.”

Some say that the bias demonstrated by the Annals study is at least partially driven by the litigation process itself. It is an adversarial system. As such, attorneys on both sides are naturally inclined to seek out doctors who will best support their clients’ cases. Doctors with a legitimately conservative perspective on what constitutes black lung are more sought after by the coal companies’ attorneys.

“It can often be impossible to tell whether the money is driving a change in the behavior or if the behavior is causing them to be sought out,” said Matt McCoy, PhD, a medical ethicist who specializes in conflicts of interest at the University of Pennsylvania, Philadelphia.

Although some believe that certain doctors are driven purely by financial incentive and offer a specific reading to secure repeat business, B-readers can end up working exclusively for companies because of other reasons. Wes Addington, JD, an attorney at the Appalachian Citizens’ Law Center, Whitesburg, Ky., said some doctors appear to have an authentically different – often antiquated – view of the disease.

Perhaps the most extreme example is Paul Wheeler, MD, a highly credentialed Johns Hopkins radiologist who was exposed for false medical testimony in Chris Hamby’s 2013 Pulitzer Prize reporting. In 1,500 readings, Dr. Wheeler never diagnosed a single case of severe black lung. And yet, Dr. Cohen, Mr. Addington, Mr. Smith, and other experts all agree that Dr. Wheeler appeared to wholeheartedly believe that his view of black lung was accurate. That made him a valuable asset to mining companies.

Since Dr. Wheeler’s exposure, there has been a greater sense of accountability among B-readers, said John Cline, JD, a West Virginia–based attorney who represents miners with federal black lung claims. “Radiologists were thinking, ‘Somebody could be watching me.’ Even if they thought they were doing this in the shadows, it made people more cautious,” he said.

The data used in the Annals study predate Mr. Hamby’s investigation, going back to 2000. Thus, it is possible that, as Mr. Cline argues, things may be different now. However, Lee S. Friedman, PhD, associate professor at the University of Illinois at Chicago, who is the lead author of the study, remains skeptical.

“While the Wheeler case might have dampened some physicians [who were] completely skewing their readings always negative, I think it’s premature or incorrect” to say it resolved the issue, he said. “Did they all change their behavior the morning after? It doesn’t seem likely, given the evidence of financial conflicts of interest and behavior that’s been demonstrated.”
 

Skewing the evidence?

Mr. Hamby’s 2013 reporting also revealed that even when company-hired doctors did diagnose CWP, law firms were burying those readings. In 2016, the DOL attempted to stop this practice. The agency made suppression of written evidence illegal – emphasis on written.

Law firms can’t hide positive reports, but they can prevent them. Dr. Cohen explained that now, “a doctor on the phone says, ‘I will read this as positive.’ Then the company says, ‘No, thank you,’ we will send you a check.”

This practice was confirmed by Kim Adcock, MD, a retired radiologist and B-reader in Littleton, Colo., who primarily reads for 26 law firms. Some of his clients want a report no matter how he reads the radiograph. However, some want him to call them first if he’s going to read the radiograph as positive. Dr. Adcock said this practice skews the dataset to make company-hired docs appear to read more negatively than they actually do.

Because the dataset used in the study is from the Federal Black Lung Program (FBLP), it includes only readings that made it to court. Dr. Adcock said he reads approximately 2,000 radiographs a year, although only a few of his readings appeared in the study’s dataset, according to a search by Dr. Friedman. This difference is likely because the study evaluated only readings between 2000 and 2013, the year Dr. Adcock started B-reading.

“I think it’s important to get a message that, to a certain extent, contravenes this paper. Yes, we should have some reservations about the conclusions,” Dr. Adcock explained. “There are people out there attempting to do the best job they could do.”

Law firms shopping for the reading they want and censoring the ones they don’t might alter the FBLP data, but experts say that doesn’t change the underlying problem. “In any case like this, where you’re looking at individuals going up against corporations,” Dr. McCoy said, “[corporations] are able to marshal their resources and hire more officials in a way claimants can’t, and that’s a baseline concern here.”
 

Battling bias

Admitting bias is notoriously difficult; thus, it isn’t surprising that many doctors involved refuse to believe they are influenced by money, incentives, or other biases. Dr. DePonte said she’s not swayed by money, nor does she actively take a pro-miner stance. She views herself as more of an advocate for accuracy. However, she did say that it has traditionally been far more difficult for miners to prove their cases, a problem that has improved with new regulations in recent years.

In Colorado, Dr. Adcock’s approach is to stay as far removed from the litigation process as possible. He said he has limited understanding of how his reports are used or how claims are filed and awarded. He leans heavily on his initial – almost instantaneous – impression of a chest x-ray.

Dr. DePonte and Dr. Adcock were both hired as experts on Tony Adams’ case. In 2008, Dr. DePonte read his chest x-ray as positive for early-stage black lung (1/0). Dr. Adcock also read two of Adams’ four chest x-rays, one in 2009 and the other in 2013. He read them as negative. When asked about the case, which autopsy confirmed as black lung, Dr. Adcock explained that positive histopathology doesn’t mean the radiograph reading was wrong, only that the disease didn’t show on that radiograph. He said his “highest ambition” is to be “an objective finder of fact” and that he trusts the process to work out the truth.

That process didn’t work in time for Tony Adams. Dr. Friedman argues that people who provide expert testimony have an ethical responsibility to know how their testimony is being used; to do otherwise, he says, is “willful ignorance.” Still, the Annals study authors, along with Dr. DePonte, Mr. Cline, and West Virginia attorney Sam Petsonk, say that the process is getting fairer, thanks to new policies developed over the past 5 years by the DOL.

“The DOL has worked very hard to reconcile the final award rate (around 30%) with the incidence of disease in the population (between 20% and 25%),” Mr. Petsonk said. Although the study calls into question the integrity of the system and the doctors within it, it’s critical for miners to know that the system is working and that they can get benefits, he explained. Many fear that cynicism about the system drives miners away and causes them to resort to Social Security or long-term disability.
 

Fixing what’s broken

The Annals study’s authors propose some solutions to the problems they quantified. The first is a sort of “super panel” that collectively evaluates readings. Although a completely unbiased panel would be nice, such impartiality is likely unsustainable, Mr. Smith said. He believes that over time, the panel would become vulnerable to politics and would work in favor of the companies.

Even without a panel, a method to provide greater transparency could be a great start, some suggest. The DOL could make the entire FBLP database public and analyze it annually. The authors also propose a flat fee for readings. Even now, Dr. Adcock said he doesn’t make anywhere close to the upper limit of $750 per readings. “My understanding is around $125 is a pretty characteristic fee [for reading a chest x-ray],” he elaborated. “Everyone I’ve had a conversation with is within 25 bucks [of that].”

That said, Dr. Adcock is not currently listed among the heavy readers who appear in the data used for the study; it’s possible that his experience is not representative. Some readers who were included in that dataset read more than 10 times the average number of classifications per reader – the average was 242 classifications – and read 95% of chest x-rays as negative, according to Dr. Friedman. This news organization obtained the names of two doctors whose readings were 95% negative on a high volume of cases. Neither agreed to an interview.

It’s possible that if the dataset had included readings from more recent years, Dr. Adcock would have appeared more frequently, given his personal estimates. That’s why the study authors recommend that the DOL conduct this kind of analysis annually in order to get an accurate picture of who is contributing to these cases, in what way, and how often. By doing so, readers who appear biased could be identified and addressed with more regularity, Dr. Friedman said.

Even if the rate were more consistent and the data were more frequently analyzed, the very nature of the adversarial system will put any potential solution at risk. “I’m not sure there’s a foolproof system that can be devised that can’t be corrupted in time,” Mr. Cline said.
 

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

In 2008, the U.S. Department of Labor (DOL) paid for Tony Adams, a 48-year-old coal miner, to have a chest x-ray. His doctor found stage I black lung disease. Yet Mr. Adams’ claim for medical benefits was denied. This was because the insurance group that represented his employer hired a different – more credentialed – doctor as its medical expert. That doctor said he saw no such evidence. The judge ruled in favor of the mining company on the basis of the latter’s “expertise.”

Before he died 5 years later, at age 53, Mr. Adams went through this process again. In fact, he did it four more times. Each time, his doctor found evidence of black lung, but the company’s medical expert did not. He died without receiving benefits. Among the causes of death listed on his autopsy were cardiopulmonary arrest and coal worker’s pneumoconiosis (CWP): black lung.

Since his death in 2013, two judges have awarded Mr. Adams’ benefits to his widow, Linda. Both times, the mining company appealed the decision, most recently in December 2020. She’s not giving up. “Two weeks before he died, he told me, ‘I’m going to die of black lung,’ ” Linda recalled. “‘But I don’t want you to give up on black lung. There are too many people screwing these miners out of what they deserve.’”

There has long been suspicion among miners and their advocates that doctors used by coal companies to fight claims like Mr. Adams’ are in the pocket of “Big Coal.” At the very least, some say these physicians are swayed by their client’s preference when reading a coal miner’s chest x-ray. A recent study published in Annals of the American Thoracic Society provides empirical evidence that these doctors’ conflict of interest – namely, that parties representing coal companies hired them – appears to influence their medical opinion.
 

Proof of a ‘broken system’

The Annals study examined 63,780 radiograph classifications made by 264 physicians – all certified as B-readers, a certification by the National Institute for Occupational Safety and Health (NIOSH) for physicians who demonstrate proficiency in classifying radiographs of pneumoconiosis. The results showed that doctors hired by miners identified black lung 49% of the time; those hired by coal companies identified black lung only 15% of the time.

The study also found that B-readers contracted by employers read results differently for different clients. The same doctors were significantly less likely to say a miner’s lungs were negative for CWP when they were hired by the DOL (77.2%) than when they were hired by a coal company or its insurers (90.2%).

The bias does appear to work both ways: B-readers hired by miners and miners’ attorneys were more likely to find evidence of black lung when they worked with plaintiffs. However, a much higher number of doctors appeared to be biased in favor of the companies. “There were 3X more B-readers providing 8X more classifications among those affiliated with employers compared to those affiliated with miners,” the study concluded.

The authors suggest that one reason for this was the difference in pay. Some company-hired doctors made as much as $750 per reading, about 10 times what miner-hired doctors were paid.

“We knew [about the potential bias] from our work over the decades taking care of these guys,” said Robert A. Cohen, MD, a pulmonologist and the study’s senior author. “But then you see it with P values that are incredibly statistically significant ...”

The study finally put numbers to a problem that many working with black lung claims had always assumed. Those within the system are accustomed to seeing names of the same doctors on documents and reports, with little to no overlap between those hired by the defense and the plaintiffs.

“The vast majority of the time, we know what a report will say based on the doctor’s name,” said Evan Smith, JD, advocacy director at AppalReD Legal Aid, in Prestonsburg, Ky.. It is far more surprising, he said, when a defense-hired doctor agrees with a miner-hired doctor.

Over the years, Katherine DePonte, MD, a radiologist and B-reader in West Virginia, has often seen an “almost textbook appearance” of CWP, only to later learn that “another radiologist read it as negative.” She explained, “They would use some other term, like ‘old granulomatous disease.’”

Employer-hired doctors often do acknowledge the same lung damage on the radiograph as miner-hired docs; they simply don’t attribute it to coal dust. Common “alternative diagnoses” include chronic obstructive pulmonary disease or histoplasmosis. “I know a number don’t believe this disease of coal worker pneumoconiosis exists [at all],” Dr. DePonte said.

What’s inarguable is that, even as coal mining in Appalachia is on the decline, black lung disease is on the rise. NIOSH now estimates that it affects over 20% of long-term (25+ years) coal workers in central Appalachia. That’s the highest prevalence in a quarter of a century.

Mr. Smith said that at its most basic level, these doctors’ conflicts of interest “lead to people who have the disease that these benefits are for, having them denied.” People like Tony Adams. Whether the doctors involved are complicit or just conservative, critics say they have become a fixture of a broken system.
 

Financial bias or difference of opinion?

Broken system or not, evidence suggests that the problem can’t be blamed solely on medical experts. Dr. DePonte primarily reads for the DOL and miners. “Not that I necessarily chose that,” she said. “You get pigeonholed.”

Some say that the bias demonstrated by the Annals study is at least partially driven by the litigation process itself. It is an adversarial system. As such, attorneys on both sides are naturally inclined to seek out doctors who will best support their clients’ cases. Doctors with a legitimately conservative perspective on what constitutes black lung are more sought after by the coal companies’ attorneys.

“It can often be impossible to tell whether the money is driving a change in the behavior or if the behavior is causing them to be sought out,” said Matt McCoy, PhD, a medical ethicist who specializes in conflicts of interest at the University of Pennsylvania, Philadelphia.

Although some believe that certain doctors are driven purely by financial incentive and offer a specific reading to secure repeat business, B-readers can end up working exclusively for companies because of other reasons. Wes Addington, JD, an attorney at the Appalachian Citizens’ Law Center, Whitesburg, Ky., said some doctors appear to have an authentically different – often antiquated – view of the disease.

Perhaps the most extreme example is Paul Wheeler, MD, a highly credentialed Johns Hopkins radiologist who was exposed for false medical testimony in Chris Hamby’s 2013 Pulitzer Prize reporting. In 1,500 readings, Dr. Wheeler never diagnosed a single case of severe black lung. And yet, Dr. Cohen, Mr. Addington, Mr. Smith, and other experts all agree that Dr. Wheeler appeared to wholeheartedly believe that his view of black lung was accurate. That made him a valuable asset to mining companies.

Since Dr. Wheeler’s exposure, there has been a greater sense of accountability among B-readers, said John Cline, JD, a West Virginia–based attorney who represents miners with federal black lung claims. “Radiologists were thinking, ‘Somebody could be watching me.’ Even if they thought they were doing this in the shadows, it made people more cautious,” he said.

The data used in the Annals study predate Mr. Hamby’s investigation, going back to 2000. Thus, it is possible that, as Mr. Cline argues, things may be different now. However, Lee S. Friedman, PhD, associate professor at the University of Illinois at Chicago, who is the lead author of the study, remains skeptical.

“While the Wheeler case might have dampened some physicians [who were] completely skewing their readings always negative, I think it’s premature or incorrect” to say it resolved the issue, he said. “Did they all change their behavior the morning after? It doesn’t seem likely, given the evidence of financial conflicts of interest and behavior that’s been demonstrated.”
 

Skewing the evidence?

Mr. Hamby’s 2013 reporting also revealed that even when company-hired doctors did diagnose CWP, law firms were burying those readings. In 2016, the DOL attempted to stop this practice. The agency made suppression of written evidence illegal – emphasis on written.

Law firms can’t hide positive reports, but they can prevent them. Dr. Cohen explained that now, “a doctor on the phone says, ‘I will read this as positive.’ Then the company says, ‘No, thank you,’ we will send you a check.”

This practice was confirmed by Kim Adcock, MD, a retired radiologist and B-reader in Littleton, Colo., who primarily reads for 26 law firms. Some of his clients want a report no matter how he reads the radiograph. However, some want him to call them first if he’s going to read the radiograph as positive. Dr. Adcock said this practice skews the dataset to make company-hired docs appear to read more negatively than they actually do.

Because the dataset used in the study is from the Federal Black Lung Program (FBLP), it includes only readings that made it to court. Dr. Adcock said he reads approximately 2,000 radiographs a year, although only a few of his readings appeared in the study’s dataset, according to a search by Dr. Friedman. This difference is likely because the study evaluated only readings between 2000 and 2013, the year Dr. Adcock started B-reading.

“I think it’s important to get a message that, to a certain extent, contravenes this paper. Yes, we should have some reservations about the conclusions,” Dr. Adcock explained. “There are people out there attempting to do the best job they could do.”

Law firms shopping for the reading they want and censoring the ones they don’t might alter the FBLP data, but experts say that doesn’t change the underlying problem. “In any case like this, where you’re looking at individuals going up against corporations,” Dr. McCoy said, “[corporations] are able to marshal their resources and hire more officials in a way claimants can’t, and that’s a baseline concern here.”
 

Battling bias

Admitting bias is notoriously difficult; thus, it isn’t surprising that many doctors involved refuse to believe they are influenced by money, incentives, or other biases. Dr. DePonte said she’s not swayed by money, nor does she actively take a pro-miner stance. She views herself as more of an advocate for accuracy. However, she did say that it has traditionally been far more difficult for miners to prove their cases, a problem that has improved with new regulations in recent years.

In Colorado, Dr. Adcock’s approach is to stay as far removed from the litigation process as possible. He said he has limited understanding of how his reports are used or how claims are filed and awarded. He leans heavily on his initial – almost instantaneous – impression of a chest x-ray.

Dr. DePonte and Dr. Adcock were both hired as experts on Tony Adams’ case. In 2008, Dr. DePonte read his chest x-ray as positive for early-stage black lung (1/0). Dr. Adcock also read two of Adams’ four chest x-rays, one in 2009 and the other in 2013. He read them as negative. When asked about the case, which autopsy confirmed as black lung, Dr. Adcock explained that positive histopathology doesn’t mean the radiograph reading was wrong, only that the disease didn’t show on that radiograph. He said his “highest ambition” is to be “an objective finder of fact” and that he trusts the process to work out the truth.

That process didn’t work in time for Tony Adams. Dr. Friedman argues that people who provide expert testimony have an ethical responsibility to know how their testimony is being used; to do otherwise, he says, is “willful ignorance.” Still, the Annals study authors, along with Dr. DePonte, Mr. Cline, and West Virginia attorney Sam Petsonk, say that the process is getting fairer, thanks to new policies developed over the past 5 years by the DOL.

“The DOL has worked very hard to reconcile the final award rate (around 30%) with the incidence of disease in the population (between 20% and 25%),” Mr. Petsonk said. Although the study calls into question the integrity of the system and the doctors within it, it’s critical for miners to know that the system is working and that they can get benefits, he explained. Many fear that cynicism about the system drives miners away and causes them to resort to Social Security or long-term disability.
 

Fixing what’s broken

The Annals study’s authors propose some solutions to the problems they quantified. The first is a sort of “super panel” that collectively evaluates readings. Although a completely unbiased panel would be nice, such impartiality is likely unsustainable, Mr. Smith said. He believes that over time, the panel would become vulnerable to politics and would work in favor of the companies.

Even without a panel, a method to provide greater transparency could be a great start, some suggest. The DOL could make the entire FBLP database public and analyze it annually. The authors also propose a flat fee for readings. Even now, Dr. Adcock said he doesn’t make anywhere close to the upper limit of $750 per readings. “My understanding is around $125 is a pretty characteristic fee [for reading a chest x-ray],” he elaborated. “Everyone I’ve had a conversation with is within 25 bucks [of that].”

That said, Dr. Adcock is not currently listed among the heavy readers who appear in the data used for the study; it’s possible that his experience is not representative. Some readers who were included in that dataset read more than 10 times the average number of classifications per reader – the average was 242 classifications – and read 95% of chest x-rays as negative, according to Dr. Friedman. This news organization obtained the names of two doctors whose readings were 95% negative on a high volume of cases. Neither agreed to an interview.

It’s possible that if the dataset had included readings from more recent years, Dr. Adcock would have appeared more frequently, given his personal estimates. That’s why the study authors recommend that the DOL conduct this kind of analysis annually in order to get an accurate picture of who is contributing to these cases, in what way, and how often. By doing so, readers who appear biased could be identified and addressed with more regularity, Dr. Friedman said.

Even if the rate were more consistent and the data were more frequently analyzed, the very nature of the adversarial system will put any potential solution at risk. “I’m not sure there’s a foolproof system that can be devised that can’t be corrupted in time,” Mr. Cline said.
 

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

Highly trained nurse practitioners (NPs) and physician assistants (PAs) are just as capable of performing screening colonoscopies as gastroenterologists: This is the conclusion from a number of studies conducted across both the United States and Europe. 

So, why aren’t more NPs and PAs doing them?

“We wanted it to take off, but we haven’t been able to do it,” said San Diego gastroenterologist Daniel “Stony” Anderson, MD. He spent decades working to expand access to colorectal cancer screening at Kaiser Permanente and other health care organizations, and he has now been doing the same as president of the California Colorectal Cancer Coalition.

Anderson told this news organization that he isn’t sure why the practice did not catch on but added, “I don’t see a groundswell for this.”

One explanation has been that the centers abandoned the practice because there were enough gastroenterologists to handle the demand.

Or perhaps it was one battle too many for NPs and PAs, who are fighting at the state level and at Veterans Affairs (VA) for permission to deliver more primary care and anesthesia services.

In addition, doctors are fighting back.

The American Medical Association runs a Stop Scope Creep campaign that opposes attempts by NPs and PAs “to inappropriately expand their scope of practice.” Along with anesthesiologists, the AMA is fighting the extension of a COVID-19 waiver at the VA that allows NPs and PAs to continue delivering anesthesia without a physician’s supervision. Other groups have joined in the battle against practice expansion via social media under the hashtags #stopscopecreep and #patientsafetymatters.

The battle is ongoing and ugly at times.

Proponents describe NPs and PAs as “advanced practice providers” but opponents call them “midlevel practitioners.” One website called Midlevel WTF argues that the health care system is declining, in part, because of “the proliferation of poorly supervised or completely unsupervised midlevels across the health care spectrum.” 
 

NPs perform colonoscopies ‘safely and effectively’ 

One of the studies to examine the issue of NPs performing screening colonoscopies, and how this compares with gastroenterologists performing the procedure, was published in Endoscopy International Open in October 2020.

In a retrospective analysis from Johns Hopkins Hospital in Baltimore, the authors concluded that three fellowship-trained NPs satisfied the American College of Gastroenterology’s quality indicators and “demonstrated that adequately trained NPs can perform colonoscopy safely and effectively.”

There was little reaction to this conclusion when the study was published. But some months later, several gastroenterologists on social media began questioning the high percentage of African Americans in the study and suggested that the research exploited Black patients, according to a story in STAT, a national health news website.

In a written statement, Hopkins said in an interview, from 2010 to 2016, patients were given the option to have an NP or physician provide a screening colonoscopy. However, they are no longer offered that option. The project has been discontinued: The gastroenterologist who was overseeing the clinical program, Anthony Kalloo, MD, director of the division of gastroenterology and hepatology, left John Hopkins earlier this year, and two of the three NPs involved in the program have also left.

Dr. Kalloo declined to comment but was quoted at length in the STAT article. He noted that NPs regularly perform colonoscopies in the United Kingdom and that the John Hopkins study showed, for the first time, “that we could do this in the United States, and the implication of that is cost savings.”

Dr. Kalloo also defended his work against claims of racial exploitation. In fact, he said, “I found those comments to be amusing. ... Obviously, they saw that I was the lead author from Hopkins, but they obviously didn’t know what I look like.” Dr. Kalloo is Black.

Dr. Kalloo is now chair of the department of medicine at Maimonides Medical Center, New York City, and he told STAT that he was interested in starting up a similar project there to train NPs to perform colonoscopies.

Other centers that explored the practice have also not continued with it.

A 2008 study at the University of California, Davis, notes: “Several barriers to colorectal cancer screening have been identified, including limited access to trained endoscopists and highlight insufficient capacity to meet projected demand for colonoscopies. ... Training NPs to perform colonoscopy may be an effective strategy to increase access.”

The study compared 100 screening colonoscopies performed by board certified gastroenterologists (GI-MD) and 50 performed by a gastroenterology-trained NP (GI-NP). There were no complications reported among the 150 cases, and “the GI-NP in our study performed screening colonoscopy as safely, accurately, and satisfactorily as the GI-MDs,” the authors conclude. 

But it’s not a strategy the hospital adopted. The nurse who conducted the study said in an interview that she is no longer doing them and declined further comment. The University of California, Davis could not confirm whether anyone else is.
 

An uncommon practice

The American Gastroenterological Association (AGA) referred questions from this news organization to the American Society for Gastrointestinal Endoscopy (ASGE).

It is very uncommon to have NPs do coloscopies, commented Douglas K. Rex, MD, director of endoscopy at Indiana University, Indianapolis, and incoming ASGE president.

“There was more of a movement the United Kingdom, but not in the United States,” he said. “I can’t tell you the reason. It’s a combination of minimal data and also the fact that there are plenty of gastroenterologists.”

The ASGE guidelines for endoscopy by nonphysicians concludes: “There are insufficient data to support nonphysician endoscopists to perform colonoscopy.”

Asked about concerns that the demand for colonoscopies will increase now that the recommendation is to start colorectal cancer screening at 45 years old, Dr. Rex said he thinks the system has enough capacity.

But will it continue to be sufficient? In a 2020 white paper on colorectal cancer screening, the AGA noted that lowering the starting age to 45 years will add 21 million people to the current pool of 94 million eligible for screening, an increase of 22%.

Lukejohn Day, MD, a gastroenterologist at the University of California, San Francisco, has reviewed the data collected on nonphysicians performing colorectal cancer screening. He led a meta-analysis of 24 studies conducted from 1997 to 2011, and the team concluded that “nonphysicians can safely perform endoscopic procedures with similar quality, especially with respect to screening flexible sigmoidoscopy. Far fewer data was reported for nonphysicians performing colonoscopy and upper endoscopy, but among this data nonphysicians perform both procedures within accepted national benchmarks for quality measures used in endoscopy.”

Dr. Day told this news organization that he had trained two NPs to do colonoscopies and did the study to get a better sense of the practice. Even still, he said the NPs required extensive training before they could perform the procedure. 

“It’s not like someone could finish school and become an endoscopist. It requires a very rigorous training program – a lot of education and mentoring,” he said. “Their program is very similar to what our GI fellows go through.”

Dr. Day said they faced opposition from the gastroenterologists, but they “had enough guardrails” in place to convince skeptics.

One of those guardrails was the requirement that an attending physician be in the building. But when San Francisco General Hospital moved to a new facility, they were unable to guarantee that coverage and the program ended, Dr. Day said.
 

Quality and depth of training hard to replicate

One place where both NPs and PAs do colonoscopies is at the VA. However, the administration doesn’t keep track of how many work there, according to a VA spokesperson. Regulations on physician providers also vary from state to state, and that is reflected in its workforce.

At the St. Louis VA Medical Center, PAs have been performing diagnostic and colorectal cancer screening colonoscopies for nearly 20 years, according to a 2020 article on the quality of care delivered by PAs. The researchers looked at data from more than 700 patients treated over a year. They had colonoscopies performed by one of seven gastroenterologists, five PAs, or 32 GI fellows from two academic affiliates. The PAs performed better than the fellows and just as well as the gastroenterologists, they concluded. 

Samir Gupta, MD, chief of gastroenterology at the VA San Diego Healthcare System, California, said in an email that he thinks a range of clinically licensed health care providers can be trained to do high-quality colonoscopy.

“The challenge has been ensuring training structure and volume of cases sufficient to consistently enable high-quality colonoscopy practice, including achieving adequate rates of polyp detection and removal and complete exams,” he wrote.

This is a challenge for gastroenterologists, but they receive ongoing medical education, and, in many settings, quality is closely monitored and managed, he wrote. He added that in a 3-year training program, most fellows do hundreds of colonoscopies.

“It is really hard to replicate this quality and depth of training outside of a GI fellowship,” Dr. Gupta said.

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

Highly trained nurse practitioners (NPs) and physician assistants (PAs) are just as capable of performing screening colonoscopies as gastroenterologists: This is the conclusion from a number of studies conducted across both the United States and Europe. 

So, why aren’t more NPs and PAs doing them?

“We wanted it to take off, but we haven’t been able to do it,” said San Diego gastroenterologist Daniel “Stony” Anderson, MD. He spent decades working to expand access to colorectal cancer screening at Kaiser Permanente and other health care organizations, and he has now been doing the same as president of the California Colorectal Cancer Coalition.

Anderson told this news organization that he isn’t sure why the practice did not catch on but added, “I don’t see a groundswell for this.”

One explanation has been that the centers abandoned the practice because there were enough gastroenterologists to handle the demand.

Or perhaps it was one battle too many for NPs and PAs, who are fighting at the state level and at Veterans Affairs (VA) for permission to deliver more primary care and anesthesia services.

In addition, doctors are fighting back.

The American Medical Association runs a Stop Scope Creep campaign that opposes attempts by NPs and PAs “to inappropriately expand their scope of practice.” Along with anesthesiologists, the AMA is fighting the extension of a COVID-19 waiver at the VA that allows NPs and PAs to continue delivering anesthesia without a physician’s supervision. Other groups have joined in the battle against practice expansion via social media under the hashtags #stopscopecreep and #patientsafetymatters.

The battle is ongoing and ugly at times.

Proponents describe NPs and PAs as “advanced practice providers” but opponents call them “midlevel practitioners.” One website called Midlevel WTF argues that the health care system is declining, in part, because of “the proliferation of poorly supervised or completely unsupervised midlevels across the health care spectrum.” 
 

NPs perform colonoscopies ‘safely and effectively’ 

One of the studies to examine the issue of NPs performing screening colonoscopies, and how this compares with gastroenterologists performing the procedure, was published in Endoscopy International Open in October 2020.

In a retrospective analysis from Johns Hopkins Hospital in Baltimore, the authors concluded that three fellowship-trained NPs satisfied the American College of Gastroenterology’s quality indicators and “demonstrated that adequately trained NPs can perform colonoscopy safely and effectively.”

There was little reaction to this conclusion when the study was published. But some months later, several gastroenterologists on social media began questioning the high percentage of African Americans in the study and suggested that the research exploited Black patients, according to a story in STAT, a national health news website.

In a written statement, Hopkins said in an interview, from 2010 to 2016, patients were given the option to have an NP or physician provide a screening colonoscopy. However, they are no longer offered that option. The project has been discontinued: The gastroenterologist who was overseeing the clinical program, Anthony Kalloo, MD, director of the division of gastroenterology and hepatology, left John Hopkins earlier this year, and two of the three NPs involved in the program have also left.

Dr. Kalloo declined to comment but was quoted at length in the STAT article. He noted that NPs regularly perform colonoscopies in the United Kingdom and that the John Hopkins study showed, for the first time, “that we could do this in the United States, and the implication of that is cost savings.”

Dr. Kalloo also defended his work against claims of racial exploitation. In fact, he said, “I found those comments to be amusing. ... Obviously, they saw that I was the lead author from Hopkins, but they obviously didn’t know what I look like.” Dr. Kalloo is Black.

Dr. Kalloo is now chair of the department of medicine at Maimonides Medical Center, New York City, and he told STAT that he was interested in starting up a similar project there to train NPs to perform colonoscopies.

Other centers that explored the practice have also not continued with it.

A 2008 study at the University of California, Davis, notes: “Several barriers to colorectal cancer screening have been identified, including limited access to trained endoscopists and highlight insufficient capacity to meet projected demand for colonoscopies. ... Training NPs to perform colonoscopy may be an effective strategy to increase access.”

The study compared 100 screening colonoscopies performed by board certified gastroenterologists (GI-MD) and 50 performed by a gastroenterology-trained NP (GI-NP). There were no complications reported among the 150 cases, and “the GI-NP in our study performed screening colonoscopy as safely, accurately, and satisfactorily as the GI-MDs,” the authors conclude. 

But it’s not a strategy the hospital adopted. The nurse who conducted the study said in an interview that she is no longer doing them and declined further comment. The University of California, Davis could not confirm whether anyone else is.
 

An uncommon practice

The American Gastroenterological Association (AGA) referred questions from this news organization to the American Society for Gastrointestinal Endoscopy (ASGE).

It is very uncommon to have NPs do coloscopies, commented Douglas K. Rex, MD, director of endoscopy at Indiana University, Indianapolis, and incoming ASGE president.

“There was more of a movement the United Kingdom, but not in the United States,” he said. “I can’t tell you the reason. It’s a combination of minimal data and also the fact that there are plenty of gastroenterologists.”

The ASGE guidelines for endoscopy by nonphysicians concludes: “There are insufficient data to support nonphysician endoscopists to perform colonoscopy.”

Asked about concerns that the demand for colonoscopies will increase now that the recommendation is to start colorectal cancer screening at 45 years old, Dr. Rex said he thinks the system has enough capacity.

But will it continue to be sufficient? In a 2020 white paper on colorectal cancer screening, the AGA noted that lowering the starting age to 45 years will add 21 million people to the current pool of 94 million eligible for screening, an increase of 22%.

Lukejohn Day, MD, a gastroenterologist at the University of California, San Francisco, has reviewed the data collected on nonphysicians performing colorectal cancer screening. He led a meta-analysis of 24 studies conducted from 1997 to 2011, and the team concluded that “nonphysicians can safely perform endoscopic procedures with similar quality, especially with respect to screening flexible sigmoidoscopy. Far fewer data was reported for nonphysicians performing colonoscopy and upper endoscopy, but among this data nonphysicians perform both procedures within accepted national benchmarks for quality measures used in endoscopy.”

Dr. Day told this news organization that he had trained two NPs to do colonoscopies and did the study to get a better sense of the practice. Even still, he said the NPs required extensive training before they could perform the procedure. 

“It’s not like someone could finish school and become an endoscopist. It requires a very rigorous training program – a lot of education and mentoring,” he said. “Their program is very similar to what our GI fellows go through.”

Dr. Day said they faced opposition from the gastroenterologists, but they “had enough guardrails” in place to convince skeptics.

One of those guardrails was the requirement that an attending physician be in the building. But when San Francisco General Hospital moved to a new facility, they were unable to guarantee that coverage and the program ended, Dr. Day said.
 

Quality and depth of training hard to replicate

One place where both NPs and PAs do colonoscopies is at the VA. However, the administration doesn’t keep track of how many work there, according to a VA spokesperson. Regulations on physician providers also vary from state to state, and that is reflected in its workforce.

At the St. Louis VA Medical Center, PAs have been performing diagnostic and colorectal cancer screening colonoscopies for nearly 20 years, according to a 2020 article on the quality of care delivered by PAs. The researchers looked at data from more than 700 patients treated over a year. They had colonoscopies performed by one of seven gastroenterologists, five PAs, or 32 GI fellows from two academic affiliates. The PAs performed better than the fellows and just as well as the gastroenterologists, they concluded. 

Samir Gupta, MD, chief of gastroenterology at the VA San Diego Healthcare System, California, said in an email that he thinks a range of clinically licensed health care providers can be trained to do high-quality colonoscopy.

“The challenge has been ensuring training structure and volume of cases sufficient to consistently enable high-quality colonoscopy practice, including achieving adequate rates of polyp detection and removal and complete exams,” he wrote.

This is a challenge for gastroenterologists, but they receive ongoing medical education, and, in many settings, quality is closely monitored and managed, he wrote. He added that in a 3-year training program, most fellows do hundreds of colonoscopies.

“It is really hard to replicate this quality and depth of training outside of a GI fellowship,” Dr. Gupta said.

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

Highly trained nurse practitioners (NPs) and physician assistants (PAs) are just as capable of performing screening colonoscopies as gastroenterologists: This is the conclusion from a number of studies conducted across both the United States and Europe. 

So, why aren’t more NPs and PAs doing them?

“We wanted it to take off, but we haven’t been able to do it,” said San Diego gastroenterologist Daniel “Stony” Anderson, MD. He spent decades working to expand access to colorectal cancer screening at Kaiser Permanente and other health care organizations, and he has now been doing the same as president of the California Colorectal Cancer Coalition.

Anderson told this news organization that he isn’t sure why the practice did not catch on but added, “I don’t see a groundswell for this.”

One explanation has been that the centers abandoned the practice because there were enough gastroenterologists to handle the demand.

Or perhaps it was one battle too many for NPs and PAs, who are fighting at the state level and at Veterans Affairs (VA) for permission to deliver more primary care and anesthesia services.

In addition, doctors are fighting back.

The American Medical Association runs a Stop Scope Creep campaign that opposes attempts by NPs and PAs “to inappropriately expand their scope of practice.” Along with anesthesiologists, the AMA is fighting the extension of a COVID-19 waiver at the VA that allows NPs and PAs to continue delivering anesthesia without a physician’s supervision. Other groups have joined in the battle against practice expansion via social media under the hashtags #stopscopecreep and #patientsafetymatters.

The battle is ongoing and ugly at times.

Proponents describe NPs and PAs as “advanced practice providers” but opponents call them “midlevel practitioners.” One website called Midlevel WTF argues that the health care system is declining, in part, because of “the proliferation of poorly supervised or completely unsupervised midlevels across the health care spectrum.” 
 

NPs perform colonoscopies ‘safely and effectively’ 

One of the studies to examine the issue of NPs performing screening colonoscopies, and how this compares with gastroenterologists performing the procedure, was published in Endoscopy International Open in October 2020.

In a retrospective analysis from Johns Hopkins Hospital in Baltimore, the authors concluded that three fellowship-trained NPs satisfied the American College of Gastroenterology’s quality indicators and “demonstrated that adequately trained NPs can perform colonoscopy safely and effectively.”

There was little reaction to this conclusion when the study was published. But some months later, several gastroenterologists on social media began questioning the high percentage of African Americans in the study and suggested that the research exploited Black patients, according to a story in STAT, a national health news website.

In a written statement, Hopkins said in an interview, from 2010 to 2016, patients were given the option to have an NP or physician provide a screening colonoscopy. However, they are no longer offered that option. The project has been discontinued: The gastroenterologist who was overseeing the clinical program, Anthony Kalloo, MD, director of the division of gastroenterology and hepatology, left John Hopkins earlier this year, and two of the three NPs involved in the program have also left.

Dr. Kalloo declined to comment but was quoted at length in the STAT article. He noted that NPs regularly perform colonoscopies in the United Kingdom and that the John Hopkins study showed, for the first time, “that we could do this in the United States, and the implication of that is cost savings.”

Dr. Kalloo also defended his work against claims of racial exploitation. In fact, he said, “I found those comments to be amusing. ... Obviously, they saw that I was the lead author from Hopkins, but they obviously didn’t know what I look like.” Dr. Kalloo is Black.

Dr. Kalloo is now chair of the department of medicine at Maimonides Medical Center, New York City, and he told STAT that he was interested in starting up a similar project there to train NPs to perform colonoscopies.

Other centers that explored the practice have also not continued with it.

A 2008 study at the University of California, Davis, notes: “Several barriers to colorectal cancer screening have been identified, including limited access to trained endoscopists and highlight insufficient capacity to meet projected demand for colonoscopies. ... Training NPs to perform colonoscopy may be an effective strategy to increase access.”

The study compared 100 screening colonoscopies performed by board certified gastroenterologists (GI-MD) and 50 performed by a gastroenterology-trained NP (GI-NP). There were no complications reported among the 150 cases, and “the GI-NP in our study performed screening colonoscopy as safely, accurately, and satisfactorily as the GI-MDs,” the authors conclude. 

But it’s not a strategy the hospital adopted. The nurse who conducted the study said in an interview that she is no longer doing them and declined further comment. The University of California, Davis could not confirm whether anyone else is.
 

An uncommon practice

The American Gastroenterological Association (AGA) referred questions from this news organization to the American Society for Gastrointestinal Endoscopy (ASGE).

It is very uncommon to have NPs do coloscopies, commented Douglas K. Rex, MD, director of endoscopy at Indiana University, Indianapolis, and incoming ASGE president.

“There was more of a movement the United Kingdom, but not in the United States,” he said. “I can’t tell you the reason. It’s a combination of minimal data and also the fact that there are plenty of gastroenterologists.”

The ASGE guidelines for endoscopy by nonphysicians concludes: “There are insufficient data to support nonphysician endoscopists to perform colonoscopy.”

Asked about concerns that the demand for colonoscopies will increase now that the recommendation is to start colorectal cancer screening at 45 years old, Dr. Rex said he thinks the system has enough capacity.

But will it continue to be sufficient? In a 2020 white paper on colorectal cancer screening, the AGA noted that lowering the starting age to 45 years will add 21 million people to the current pool of 94 million eligible for screening, an increase of 22%.

Lukejohn Day, MD, a gastroenterologist at the University of California, San Francisco, has reviewed the data collected on nonphysicians performing colorectal cancer screening. He led a meta-analysis of 24 studies conducted from 1997 to 2011, and the team concluded that “nonphysicians can safely perform endoscopic procedures with similar quality, especially with respect to screening flexible sigmoidoscopy. Far fewer data was reported for nonphysicians performing colonoscopy and upper endoscopy, but among this data nonphysicians perform both procedures within accepted national benchmarks for quality measures used in endoscopy.”

Dr. Day told this news organization that he had trained two NPs to do colonoscopies and did the study to get a better sense of the practice. Even still, he said the NPs required extensive training before they could perform the procedure. 

“It’s not like someone could finish school and become an endoscopist. It requires a very rigorous training program – a lot of education and mentoring,” he said. “Their program is very similar to what our GI fellows go through.”

Dr. Day said they faced opposition from the gastroenterologists, but they “had enough guardrails” in place to convince skeptics.

One of those guardrails was the requirement that an attending physician be in the building. But when San Francisco General Hospital moved to a new facility, they were unable to guarantee that coverage and the program ended, Dr. Day said.
 

Quality and depth of training hard to replicate

One place where both NPs and PAs do colonoscopies is at the VA. However, the administration doesn’t keep track of how many work there, according to a VA spokesperson. Regulations on physician providers also vary from state to state, and that is reflected in its workforce.

At the St. Louis VA Medical Center, PAs have been performing diagnostic and colorectal cancer screening colonoscopies for nearly 20 years, according to a 2020 article on the quality of care delivered by PAs. The researchers looked at data from more than 700 patients treated over a year. They had colonoscopies performed by one of seven gastroenterologists, five PAs, or 32 GI fellows from two academic affiliates. The PAs performed better than the fellows and just as well as the gastroenterologists, they concluded. 

Samir Gupta, MD, chief of gastroenterology at the VA San Diego Healthcare System, California, said in an email that he thinks a range of clinically licensed health care providers can be trained to do high-quality colonoscopy.

“The challenge has been ensuring training structure and volume of cases sufficient to consistently enable high-quality colonoscopy practice, including achieving adequate rates of polyp detection and removal and complete exams,” he wrote.

This is a challenge for gastroenterologists, but they receive ongoing medical education, and, in many settings, quality is closely monitored and managed, he wrote. He added that in a 3-year training program, most fellows do hundreds of colonoscopies.

“It is really hard to replicate this quality and depth of training outside of a GI fellowship,” Dr. Gupta said.

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

The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.

“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”

With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.

The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.

“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”

But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.

And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)

The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.

“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.

While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.

“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.

The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.

The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.

Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.

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

The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.

“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”

With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.

The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.

“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”

But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.

And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)

The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.

“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.

While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.

“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.

The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.

The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.

Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.

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

The U.S. Occupational Safety and Health Administration issued its long-awaited Emergency Temporary Standard (ETS) for COVID-19 June 10, surprising many by including only health care workers in the new emergency workplace safety rules.

“The ETS is an overdue step toward protecting health care workers, especially those working in long-term care facilities and home health care who are at greatly increased risk of infection,” said George Washington University, Washington, professor and former Obama administration Assistant Secretary of Labor David Michaels, PhD, MPH. “OSHA’s failure to issue a COVID-specific standard in other high-risk industries, like meat and poultry processing, corrections, homeless shelters, and retail establishments is disappointing. If exposure is not controlled in these workplaces, they will continue to be important drivers of infections.”

With the new regulations in place, about 10.3 million health care workers at hospitals, nursing homes, and assisted living facilities, as well as emergency responders and home health care workers, should be guaranteed protection standards that replace former guidance.

The new protections include supplying personal protective equipment and ensuring proper usage (for example, mandatory seal checks on respirators); screening everyone who enters the facility for COVID-19; ensuring proper ventilation; and establishing physical distancing requirements (6 feet) for unvaccinated workers. It also requires employers to give workers time off for vaccination. An antiretaliation clause could shield workers who complain about unsafe conditions.

“The science tells us that health care workers, particularly those who come into regular contact with the virus, are most at risk at this point in the pandemic,” Labor Secretary Marty Walsh said on a press call. “So following an extensive review of the science and data, OSHA determined that a health care–specific safety requirement will make the biggest impact.”

But questions remain, said James Brudney, JD, a professor at Fordham Law School in New York and former chief counsel of the U.S. Senate Subcommittee on Labor. The standard doesn’t amplify or address existing rules regarding a right to refuse unsafe work, for example, so employees may still feel they are risking their jobs to complain, despite the antiretaliation clause.

And although vaccinated employees don’t have to adhere to the same distancing and masking standards in many instances, the standard doesn’t spell out how employers should determine their workers’ vaccination status – instead leaving that determination to employers through their own policies and procedures. (California’s state OSHA office rules specify the mechanism for documentation of vaccination.)

The Trump administration did not issue an ETS, saying OSHA’s general duty clause sufficed. President Joe Biden took the opposite approach, calling for an investigation into an ETS on his first day in office. But the process took months longer than promised.

“I know it’s been a long time coming,” Mr. Walsh acknowledged. “Our health care workers from the very beginning have been put at risk.

While health care unions had asked for mandated safety standards sooner, National Nurses United, the country’s largest labor union for registered nurses, still welcomed the rules.

“An ETS is a major step toward requiring accountability for hospitals who consistently put their budget goals and profits over our health and safety,” Zenei Triunfo-Cortez, RN, one of NNU’s three presidents, said in a statement June 9 anticipating the publication of the rules.

The rules do not apply to retail pharmacies, ambulatory care settings that screen nonemployees for COVID-19, or certain other settings in which all employees are vaccinated and people with suspected or confirmed COVID-19 cannot enter.

The agency said it will work with states that have already issued local regulations, including two states that issued temporary standards of their own, Virginia and California.

Employers will have 2 weeks to comply with most of the regulations after they’re published in the Federal Register. The standards will expire in 6 months but could then become permanent, as Virginia’s did in January.

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

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

mzoler@mdedge.com

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

mzoler@mdedge.com

The investigational, novel, injected once-weekly “twincretin” tirzepatide met its primary efficacy endpoint of significantly cutting hemoglobin A1c as well as its secondary weight-loss endpoint in patients with type 2 diabetes when compared with control patients in top-line results from each of five discrete pivotal trials.

Courtesy Joslin Diabetes Center

The company developing tirzepatide, Lilly, announced these results in a series of four press releases issued during December 2020–May 2021. Scientific reports on the outcomes from four of these trials are scheduled during the American Diabetes Association’s Scientific Sessions being held virtually in late June 2021, with results from the fifth on track for a report during the annual meeting of the European Association for the Study of Diabetes in September 2021.

Tirzepatide is a “twincretin” because it combines in a single molecule two different gut-hormone activities. It works as both a glucagonlike peptide–1 receptor agonist (GLP-1 RA) and as an agent that mimics the glucose-dependent insulinotropic polypeptide (GIP).

While diabetologists qualified their comments on these results because of the limited scope and format of the five reports to date, they also expressed enthusiasm over what the press releases said.
 

Results give hope

“It’s quite exciting, but of course we would like to go by the data that’s presented” at upcoming meetings, commented Robert A. Gabbay, MD, PhD, chief science and medical officer of the American Diabetes Association in Arlington, Va. “The idea of GLP-1 and GIP activities working together has been out there for a while, but without any therapeutic options that leverage this,” he said in an interview.

“The preliminary results give us hope that tirzepatide will be a very effective glucose-lowering agent, perhaps the most effective among all options currently available, including insulin,” commented Ildiko Lingvay, MD, a diabetologist and professor at the University of Texas Southwestern Medical Center, Dallas. “Tirzepatide might have the added benefit of clinically meaningful weight loss,” and “the adverse event profile seems to be in line with what we are accustomed to with the GLP-1 RA class. I look forward to seeing the full results. Tirzepatide promises to be a great addition for type 2 diabetes,” Dr. Lingvay said in an interview.
 

A rare head-to-head against semaglutide

The five phase 3, randomized controlled trials described by Lilly in its four press releases all belong to the SURPASS series of studies for this agent. Perhaps the most intriguing of the five were results from SURPASS-2, announced in a release on March 4. This trial randomized 1,879 patients from the United States or any of seven other countries to 40 weeks of open-label treatment with one of three different dosages of tirzepatide administered by injection once weekly, or to the control group that received a weekly 1-mg injection of semaglutide (Ozempic), the highest dosage approved for controlling glycemia in patients with type 2 diabetes at the time the study launched.

In SURPASS-2 all three tested dosages of tirzepatide led to a significantly larger reduction, from baseline in A1c, compared with semaglutide, after 40 weeks, according to the Lilly release. Each of the three tirzepatide dosages also led to significantly greater weight loss from baseline, compared with semaglutide, and significantly greater percentages of patients who achieved an A1c of less than 7%, compared with semaglutide.

As an example, the highest tested tirzepatide dosage of 15 mg weekly led to an average A1c reduction from baseline of 2.46% and an average weight loss from baseline of 12.4 kg; 92% of patients achieved an A1c of less than 7%, and 51% had their A1c fall below 5.7% which indicates completely normalization of glycemic control. By comparison, the patients randomized to treatment with semaglutide had an average 1.86% reduction in their A1c level from baseline and a 6.2-kg average cut in body weight from baseline; 81% achieved an A1c of less than 7%, and 20% reached an A1c of less than 5.7%.
 

There are caveats

While these findings are notable as a rare example of an industry-sponsored head-to-head comparison of two new agents, the study comes with a few important asterisks.

First, it was open label, a curious limitation given that both agents are delivered by the same delivery method and schedule. “I cannot conclude based on this study that tirzepatide is superior because it was open label,” commented Anastassia Amaro, MD, medical director of Penn Metabolic Medicine at the University of Pennsylvania, Philadelphia.

“The gold standard is the double-blind study. An open-label design is a limitation,” agreed Dr. Gabbay.

A second caveat is that the Food and Drug Administration recently approved a higher dosage of semaglutide (2.4 g once/week) for treating overweight or obesity in patients with type 2 diabetes and in those without diabetes but a different weight-related condition such as hypertension of hypercholesterolemia. This means that the tested comparator dosage of 1 mg/week is no longer the maximum that most patients treated with semaglutide for glycemic control can receive.

“The inevitable question” about this comparison study is “what about a higher semaglutide dose,” and how might tirzepatide perform relative to that, said Dr. Gabbay. The recently approved higher dosage of semaglutide “adds an interesting wrinkle.”

Lilly has launched a series of studies testing tirzepatide as a treatment for overweight or obesity in people without diabetes, but the results are not expected until sometime in 2022 or 2023.

And there’s a third caveat: Semaglutide has already shown its value for cardiovascular risk reduction in patients with type 2 diabetes in the SUSTAIN 6 trial with nearly 3,300 randomized patients followed for 2 years and reported in 2016. The cardiovascular outcomes trial for tirzepatide, SURPASS-CVOT with more than 12,000 patients with type 2 diabetes, is underway but its results are not expected until 2024.

Despite these important limitations, a blinded comparison of tirzepatide and higher-dose semaglutide is unlikely, Dr. Amaro predicted. “It’s not worth the expense,” she said in an interview. A more likely scenario will be that, if tirzepatide enters the U.S. market, decisions on whether to treat patients with it or semaglutide will pivot on factors like the cost for treatment to individual patients based on their insurance coverage and tolerability, suggested both Dr. Amaro and Dr. Gabbay. “Physicians will need to develop a sense for tirzepatide: Do patients tolerate it and are they happy using it?” Dr. Amaro said.
 

Tirzepatide versus insulin, or on top of insulin

The other four trials in patients with type 2 diabetes reported by Lilly in releases included SURPASS-1, which randomized 478 patients to treatment with tirzepatide or placebo as monotherapy; SURPASS-3, which randomized 1,444 patients to tirzepatide or insulin degludec (Tresiba) on top of background treatment with metformin; SURPASS-4, which randomized 2,002 patients with high cardiovascular disease risk to treatment with tirzepatide or insulin glargine (Lantus) on top of background treatment with one to three different oral drugs; and SURPASS-5, which randomized 475 patients to treatment with tirzepatide or placebo on top of background treatment with insulin glargine and optional addition of metformin. Altogether, the five trials randomized nearly 6,300 patients.

The studies that compared tirzepatide against two different types of insulin, and the third that tested tirzepatide on top of insulin glargine, are especially notable. “It’s good to see that the combination [of tirzepatide and insulin glargine] works without causing major adverse events,” said Dr. Amaro.

“These are fair and helpful comparisons. I applaud Lilly for doing the right kind of comparisons,” said Dr. Gabbay.

In total, the five studies “provide evidence that tirzepatide will be effective at all stages of type 2 diabetes and can safely be used in combination with other glucose-lowering agents, including insulin,” said Dr. Lingvay. The studies with active comparator agents “allow us to compare tirzepatide’s efficacy against established therapies.”

The SURPASS trials were sponsored by Lilly, which is developing tirzepatide. Dr. Gabbay had no relevant disclosures. Dr. Lingvay has received research funds, consulting and advisory fees, or other support from Lilly as well as from several other companies including Novo Nordisk, which markets semaglutide (Ozempic) and insulin degludec (Tresiba), and Sanofi, which markets insulin glargine (Lantus). Dr. Amaro has received research funding from Lilly and from Fractyl, and has been a consultant to and received research funding from Novo Nordisk.

mzoler@mdedge.com