Mixed Topics

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

Radiation oncologists from the largest professional societies have come together to lobby for Medicare payment reform.

The American Society for Radiation Oncology (ASTRO) recently announced its partnership with three other groups — the American College of Radiation Oncology, the American College of Radiology, and the American Society of Clinical Oncology — to change how the specialty is paid for services. 

Over the past decade, radiation oncologists have seen a 23% drop in Medicare reimbursement for radiation therapy services, with more cuts to come, according to a press release from ASTRO.

Traditionally, Medicare has reimbursed on the basis of the fraction of radiation delivered. But with moves toward hypofractionated regimens, deescalated therapy, and other changes in the field, reimbursement has continued to dwindle. 

The cuts have led to practice consolidation and closures that threaten patient access especially in rural and underserved areas, a spokesperson for the group told this news organization.

To reverse this trend, ASTRO recently proposed the Radiation Oncology Case Rate program, a legislative initiative to base reimbursements on patient volumes instead of fractions delivered. 

ASTRO is currently drafting a congressional bill to change the current payment structure, which “has become untenable,” the spokesperson said. 

A version of this article appeared on Medscape.com.

For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

For years, oncologist John DiPersio, MD, PhD, had faced frustrating encounters with insurers that only cover medications through a process called white bagging.

Instead of the traditional buy-and-bill pathway where oncologists purchase specialty drugs, such as infusion medications, directly from the distributor or manufacturer, white bagging requires physicians to receive these drugs from a specialty pharmacy.

On its face, the differences may seem minor. However, as Dr. DiPersio knows well, the consequences for oncologists and patients are not.

White bagging, research showed, leads to higher costs for patients and lower reimbursement for oncology practices. The practice can also create safety issues for patients.

That is why Dr. DiPersio’s cancer center does not allow white bagging.

And when insurers refuse to reconsider the white bagging policy, his cancer team is left with few options.

“Sometimes, we have to redirect patients to other places,” said Dr. DiPersio, a bone marrow transplant specialist at Siteman Cancer Center, Washington University, St. Louis.

In emergency instances where patients cannot wait, Dr. DiPersio’s team will administer their own stock of a drug. In such cases, “we accept the fact that by not allowing white bagging, there may be nonpayment. We take the hit as far as cost.”

Increasingly, white bagging mandates are becoming harder for practices to avoid.

In a 2021 survey, 87% of Association of Community Cancer Centers members said white bagging has become an insurer mandate for some of their patients.

A 2023 analysis from Adam J. Fein, PhD, of Drug Channels Institute, Philadelphia, found that white bagging accounted for 17% of infused oncology product sourcing from clinics and 38% from hospital outpatient departments, up from 15% to 28% in 2019. Another practice called brown bagging, where specialty pharmacies send drugs directly to patients, creates many of the same issues but is much less prevalent than white bagging.

This change reflects “the broader battle over oncology margins” and insurers’ “attempts to shift costs to providers, patients, and manufacturers,” Dr. Fein wrote in his 2023 report.
 

White Bagging: Who Benefits?

At its core, white bagging changes how drugs are covered and reimbursed. Under buy and bill, drugs fall under a patient’s medical benefit. Oncologists purchase drugs directly from the manufacturer or distributor and receive reimbursement from the insurance company for both the cost of the drug as well as for administering it to patients.

Under white bagging, drugs fall under a patient’s pharmacy benefit. In these instances, a specialty pharmacy prepares the infusion ahead of time and ships it directly to the physician’s office or clinic. Because oncologists do not purchase the drug directly, they cannot bill insurers for it; instead, the pharmacy receives reimbursement for the drug and the provider is reimbursed for administering it.

Insurance companies argue that white bagging reduces patients’ out-of-pocket costs “by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” according to advocacy group America’s Health Insurance Plans (AHIP).

Data from AHIP suggested that hospitals mark up the price of cancer drugs considerably, charging about twice as much as a specialty pharmacy, and that physician’s offices also charge about 23% more. However, these figures highlight how much insurers are billed, not necessarily how much patients ultimately pay.

Other evidence shows that white bagging raises costs for patients while reducing reimbursement for oncologists and saving insurance companies money.

A recent analysis in JAMA Network Open, which looked at 50 cancer drugs associated with the highest total spending from the 2020 Medicare Part B, found that mean insurance payments to providers were more than $2000 lower for drugs distributed under bagging than traditional buy and bill: $7405 vs $9547 per patient per month. Investigators found the same pattern in median insurance payments: $5746 vs $6681. Patients also paid more out-of-pocket each month with bagging vs buy and bill: $315 vs $145.

For patients with private insurance, “out-of-pocket costs were higher under bagging practice than the traditional buy-and-bill practice,” said lead author Ya-Chen Tina Shih, PhD, a professor in the department of radiation oncology at UCLA Health, Los Angeles.

White bagging is entirely for the profit of health insurers, specialty pharmacies, and pharmacy benefit managers, the middlemen who negotiate drug prices on behalf of payers.

Many people may not realize the underlying money-making strategies behind white bagging, explained Ted Okon, executive director for Community Oncology Alliance, which opposes the practice. Often, an insurer, pharmacy benefit manager, and mail order pharmacy involved in the process are all affiliated with the same corporation. In such cases, an insurer has a financial motive to control the source of medications and steer business to its affiliated pharmacies, Mr. Okon said.

When a single corporation owns numerous parts of the drug supply chain, insurers end up having “sway over what drug to use and then how the patient is going to get it,” Mr. Okon said. If the specialty pharmacy is a 340B contract pharmacy, it likely also receives a sizable discount on the drug and can make more money through white bagging.
 

Dangerous to Patients?

On the safety front, proponents of white bagging say the process is safe and efficient.

Specialty pharmacies are used only for prescription drugs that can be safely delivered, said AHIP spokesman David Allen.

In addition to having the same supply chain safety requirements as any other dispensing pharmacy, “specialty pharmacies also must meet additional safety requirements for specialty drugs” to ensure “the safe storage, handling, and dispensing of the drugs,” Mr. Allen explained.

However, oncologists argue that white bagging can be dangerous.

With white bagging, specialty pharmacies send a specified dose to practices, which does not allow practices to source and mix the drug themselves or make essential last-minute dose-related changes — something that happens every day in the clinic, said Debra Patt, MD, PhD, MBA, executive vice president for policy and strategy for Texas Oncology, Dallas.

White bagging also increases the risk for drug contamination, results in drug waste if the medication can’t be used, and can create delays in care.

Essentially, white bagging takes control away from oncologists and makes patient care more unpredictable and complex, explained Dr. Patt, president of the Texas Society of Clinical Oncology, Rockville, Maryland.

Dr. Patt, who does not allow white bagging in her practice, recalled a recent patient with metastatic breast cancer who came to the clinic for trastuzumab deruxtecan. The patient had been experiencing acute abdominal pain. After an exam and CT, Dr. Patt found the breast cancer had grown and moved into the patient’s liver.

“I had to discontinue that plan and change to a different chemotherapy,” she said. “If we had white bagged, that would have been a waste of several thousand dollars. Also, the patient would have to wait for the new medication to be white bagged, a delay that would be at least a week and the patient would have to come back at another time.”

When asked about the safety concerns associated with white bagging, Lemrey “Al” Carter, MS, PharmD, RPh, executive director of the National Association of Boards of Pharmacy (NABP), said the NABP “acknowledges that all these issues exist.

“It is unfortunate if patient care or costs are negatively impacted,” Dr. Carter said, adding that “boards of pharmacy can investigate if they are made aware of safety concerns at the pharmacy level. If a violation of the pharmacy laws or rules is found, boards can take action.”
 

More Legislation to Prevent Bagging

As white bagging mandates from insurance companies ramp up, more practices and states are banning it.

In the Association of Community Cancer Centers’ 2021 survey, 59% of members said their cancer program or practice does not allow white bagging.

At least 15 states have introduced legislation that restricts and/or prohibits white and brown bagging practices, according to a 2023 report by the Institute for Clinical and Economic Review. Some of the proposed laws would restrict mandates by stipulating that physicians are reimbursed at the contracted amount for clinician-administered drugs, whether obtained from a pharmacy or the manufacturer.

Louisiana, Vermont, and Minnesota were the first to enact anti–white bagging laws. Louisiana’s law, for example, enacted in 2021, bans white bagging and requires insurers to reimburse providers for physician-administered drugs if obtained from out-of-network pharmacies.

When the legislation passed, white bagging was just starting to enter the healthcare market in Louisiana, and the state wanted to act proactively, said Kathy W. Oubre, MS, CEO of the Pontchartrain Cancer Center, Covington, Louisiana, and president of the Coalition of Hematology and Oncology Practices, Mountain View, California.

“We recognized the growing concern around it,” Ms. Oubre said. The state legislature at the time included physicians and pharmacists who “really understood from a practice and patient perspective, the harm that policy could do.”

Ms. Oubre would like to see more legislation in other states and believes Louisiana’s law is a good model.

At the federal level, the American Hospital Association and American Society of Health-System Pharmacists have also urged the US Food and Drug Administration to take appropriate enforcement action to protect patients from white bagging.

Legislation that bars white bagging mandates is the most reasonable way to support timely and appropriate access to cancer care, Dr. Patt said. In the absence of such legislation, she said oncologists can only opt out of insurance contracts that may require the practice.

“That is a difficult position to put oncologists in,” she said.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

When it comes to the use of colonoscopy to reduce the risk for cancer, quality is key.

There are a number of performance improvements we can make in our practices so that we can do better. This is evident in several recently published studies and a recent review article on the topic, which I’d like to profile for you; many of these key quality indicators you can implement now.

Even though it may take more time before they’re supported in the guidelines, you’ll see that the evidence behind these is extraordinarily strong.
 

Increasing the Adenoma Detection Rate

Certainly, we all do what we can to increase the adenoma detection rate (ADR).

However, at the moment, the nationally recommended benchmark is to achieve an ADR of 25%, which is inordinately low. The ADR rate reported in the GIQuIC registry data is closer to 39%, and in high-level detectors, it’s actually in the greater-than-50% range.

There’s no question that we can do more, and there are a number of ways to do that.

First, we can consider using mucosal exposure techniques in our colonoscopies. These techniques incorporate the use of a hood, cap, or device that faces the mucosal folds on withdrawal from the cecum. This may actually decrease your withdrawal time because you don’t spend so much time trying to face these folds.

In considering tools to aid ADR, don’t forget electronic chromoendoscopy (eg, narrow-band imaging).

There are a number of new artificial intelligence options out there as well, which have been reported to increase the ADR by approximately 10%. Of importance, this improvement even occurs among expert endoscopists.

There’s also important emerging data about ADR in fecal immunochemical test (FIT)–positive patients. FIT-positive status increases the ADR threshold by 15%-20%. This places you in an ADR range of approximately 50%, which is really the norm when screening patients that present for colonoscopy because of FIT positivity.
 

Adenoma Per Colonoscopy: A Possible ADR Substitute

Growing evidence supports the use of adenoma per colonoscopy (APC) as a substitute to ADR. This would allow you to record every adenoma and attribute it to that index colonoscopy.

A high-quality paper showed that the APC value should be around 0.6 to achieve the current ADR minimum threshold of 25%. Having the APC < 0.6 seems to be associated with an increased risk for residual polyp. Sessile serrated lesions also increased the hazard ratio for interval colorectal cancer. This was evaluated recently with data from the New Hampshire Colonoscopy Registry, which Dr Joseph Anderson has led for so long. They showed that 21% of endoscopists had an ADR of 25% or greater but still had APCs < 0.6.

Therefore, when it comes to remedial corrective work, doctors need to be reevaluated, retrained, and educated in the ways that they can incorporate this. The APC in high-level detectors is > 1.0.

APC may be something you want to consider using internally. It does require that you place each polyp into an individual jar, which can increase incremental cost. Nonetheless, there is clear evidence that APC positively changes outcomes.
 

Including Sessile Serrated Lesions in ADR Detectors

Unfortunately, some of the high-level ADR detectors aren’t so “high level” when it comes to detecting sessile serrated lesions. It’s not quite as concordant as we had previously thought.

Nonetheless, there are many adjunctive things you can do with sessile serrated lesions, including narrow-band imaging and chromoendoscopy.

When it comes to establishing a discriminant, the numbers should be 5%-6% if we’re going to set a quality ratio and an index. However, this is somewhat dependent on your pathologist because they have to read these correctly. Lesions that are ≥ 6 mm above the sigmoid colon and anything in the right colon should be evaluated really closely as a sessile serrated lesion.

I’ve had indications where the pathologist says the lesion is hyperplastic, to which I say, “I’m going to follow as a sessile serrated lesion.” This is because it’s apparent to me in the endoscopic appearance and the narrow-band imaging appearance that it was characteristic of sessile serrated lesions.
 

Best Practices in Bowel Preparations

The US Multi-Society Task Force recommends that adequate bowel preparation should occur in 85% or more of outpatients, and for the European Society for Gastrointestinal Endoscopy, it’s 90% or more.

I’ll pass along a tip I use in my patients undergoing bowel preparation: I make them aware that during this process, they want to see a clear, yellow, urine-like color to their stool. Otherwise, many patients will think if they’ve had some diarrhea, they don’t need to finish prep. Setting that expectation for them upfront is really important.

The nurses also should be aware of this because if there’s a murky brown effluent upon presentation for the colonoscopy, there’s a greater than 50% chance that they’re going to have had an inadequate preparation. In such cases, you would want to preempt the colonoscopy and perhaps send them out for a re-prep that day or bring them back for a rescheduled appointment.
 

Resection Considerations

There is substantial variation when it comes to lesion resection, which makes it an important quality indicator on which to focus: High-level detectors aren’t always high-level resectors.

There are two validated instruments that you can use to gauge the adequacy of resection. Those aren’t really ready for prime time in every practice, though they may be seen in fellowship programs.

The idea here is that you want to get a ≥ 2 mm margin for cold snare polypectomy in lesions 1-10 mm in size. This has been a challenge, as findings indicate we don’t do this that well.

Joseph Anderson and colleagues recently published a study using a 2-mm resection margin. They reported that this was only possible in approximately 28% of polyps. For a 1-mm margin, the rate was 84%.

We simply need to set clearer margins when setting our snare. Make sure you’re close enough to the polyp, push down on the snare, and get a good margin of tissue.

When the sample contracts are placed into the formalin, it’s not quite so simple to define the margin at the time of the surgical resection. This often requires an audit evaluation by the pathologist.

There are two other considerations regarding resection.

The first is about the referral for surgery. Referral should not occur for any benign lesions ascribed by your endoscopic advanced imaging techniques and classifications that are not thought to have intramucosal carcinoma. These should be referred to an expert endoscopic evaluation. If you can’t do it, then somebody else should. And you shouldn’t attempt it unless you can get it totally because resection of partially resected lesions is much more complicated. The European Society of Gastrointestinal Endoscopy says this applies to any benign lesion of any size, which I think really is the emerging standard of care. You should consider and offer that to the patient. It may require a referral for outside of your institution.

The second additional consideration is around the minimization of cold forceps for removal of polyps. The US Multi-Society Task Force says cold forceps shouldn’t be used for any lesions > 2 mm, whereas for the European Society of Gastrointestinal Endoscopy, it is > 3 mm. However, it’s still done very commonly in clinical practice. Nibbling the polyp is not an option. Cold snare is actually quicker, more effective, has better outcomes, and is something that you can bill for when you look at the coding.

In summary, there are a lot of things that we can do now to improve colonoscopy. Quality indicators continue to emerge with a compelling, excellent evidence base that strongly supports their use. Given that, I think most of these are actionable now, and it’s not necessary to wait for the guidelines to begin using them. I’d therefore challenge all of us to incorporate them in our continual efforts to do better.

Dr. Johnson is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease. He has disclosed ties with ISOTHRIVE and Johnson & Johnson.

A version of this article appeared on Medscape.com.

To the Editor:

Cutaneous cysts commonly are treated by dermatologists and typically are diagnosed clinically, followed by intraoperative or histologic confirmation; however, cyst mimickers can be misdiagnosed due to similar appearance and limited diagnostic guidelines.¹ Vascular anomalies (VAs) of the face such as a facial aneurysm are rare.² Preoperative assessment of findings suggestive of vascular etiology vs other common cutaneous tumors such as an epidermal inclusion cyst (EIC) and lipoma can help guide dermatologic management. We present a case of a VA of the glabella manifesting as a flesh-colored nodule that clinically mimicked a cyst and discuss the subsequent surgical management.

A 61-year-old man with a history of benign prostatic hyperplasia was evaluated at our dermatology clinic for an enlarging forehead mass of 1 year’s duration. Physical examination yielded a soft, flesh-colored, 2.5-cm nodule located superficially in the midline glabellar region without pulsation or palpable thrill. The differential diagnosis at the time included lipoma or EIC.

Excision of the lesion was performed utilizing superficial incisions with a descending depth of 1-mm increments to safely reach the target, identify the type of tumor, and prevent rupture of the suspected EIC. After the third incision to the level of the dermis, nonpulsatile bleeding was more than expected for a cyst. Digital pressure was applied, and the area was explored with blunt dissection to identify the source of bleeding. A fusiform, thin-walled aneurysm was identified in the dermal plane with additional tributaries coursing deep into the subcutaneous plane. The visualized tributaries were ligated with 3-0 polyglactin, figure-of-eight sutures resulting in hemostasis. The wound was closed with 5-0 nylon simple interrupted sutures. The patient was closely followed postoperatively for 1 week (Figure) and was referred for head imaging to evaluate for a possible associated intracranial aneurysm. Based on the thin vessel wall and continuous nonpulsatile hemorrhage, this VA was most consistent with venous aneurysm.

A VA can be encountered unexpectedly during dermatologic surgery. An aneurysm is a type of VA and is defined as an abnormal dilatation of a blood vessel that can be arterial, venous, or an arteriovenous malformation. Most reported aneurysms of the head and neck are cirsoid aneurysms or involve the superficial temporal artery.^2,3 Reports of superficial venous aneurysms are rare.⁴ Preoperatively, cutaneous nodules can be evaluated for findings suggestive of a VA in the dermatologist’s office through physical examination. Arterial aneurysms may reveal palpable pulsation and audible bruit, while a venous aneurysm may exhibit a blue color, a size reduction with compression, and variable size with Valsalva maneuver.

The gold standard diagnostic tool for most dermatologic conditions is histopathology; however, dermatologic ultrasonography can provide noninvasive, real-time, important diagnostic characteristics of cutaneous pathologies as well as VA.^5-7 Crisan et al⁶ outlined specific sonographic findings of lipomas, EICs, trichilemmal cysts, and other dermatologic conditions as well as the associated surgical pertinence. Ultrasonography of a venous aneurysm may show a heterogeneous, contiguous, echoic lesion with an adjacent superficial vein, which may be easily compressed by the probe.⁸ Advanced imaging such as computed tomography with contrast or magnetic resonance imaging may be performed, but these are more costly than ultrasonography. Additionally, point-of-care ultrasonography is becoming more popular and accessible for physicians to carry at bedside with portable tablet options available. Dermatologists may want to consider incorporating it into the outpatient setting to improve procedural planning.⁹

In conclusion, VAs should be included in the differential diagnosis of soft cutaneous nodules, as management differs from a cyst or lipoma. Dermatologists should use their clinical judgment preoperatively—including a comprehensive history, physical examination, and consideration of color Doppler ultrasonography to assess for findings of VA. We do not recommend intentional surgical exploration of cutaneous aneurysms in the ambulatory setting due to risk for hemorrhage. Furthermore, when clinical suspicion of EIC or lipoma is high, it still is preferable to descend the incision slowly at 1 to 2 mm per cut until the tumor is visualized.

To the Editor:

Cutaneous cysts commonly are treated by dermatologists and typically are diagnosed clinically, followed by intraoperative or histologic confirmation; however, cyst mimickers can be misdiagnosed due to similar appearance and limited diagnostic guidelines.¹ Vascular anomalies (VAs) of the face such as a facial aneurysm are rare.² Preoperative assessment of findings suggestive of vascular etiology vs other common cutaneous tumors such as an epidermal inclusion cyst (EIC) and lipoma can help guide dermatologic management. We present a case of a VA of the glabella manifesting as a flesh-colored nodule that clinically mimicked a cyst and discuss the subsequent surgical management.

A 61-year-old man with a history of benign prostatic hyperplasia was evaluated at our dermatology clinic for an enlarging forehead mass of 1 year’s duration. Physical examination yielded a soft, flesh-colored, 2.5-cm nodule located superficially in the midline glabellar region without pulsation or palpable thrill. The differential diagnosis at the time included lipoma or EIC.

Excision of the lesion was performed utilizing superficial incisions with a descending depth of 1-mm increments to safely reach the target, identify the type of tumor, and prevent rupture of the suspected EIC. After the third incision to the level of the dermis, nonpulsatile bleeding was more than expected for a cyst. Digital pressure was applied, and the area was explored with blunt dissection to identify the source of bleeding. A fusiform, thin-walled aneurysm was identified in the dermal plane with additional tributaries coursing deep into the subcutaneous plane. The visualized tributaries were ligated with 3-0 polyglactin, figure-of-eight sutures resulting in hemostasis. The wound was closed with 5-0 nylon simple interrupted sutures. The patient was closely followed postoperatively for 1 week (Figure) and was referred for head imaging to evaluate for a possible associated intracranial aneurysm. Based on the thin vessel wall and continuous nonpulsatile hemorrhage, this VA was most consistent with venous aneurysm.

A VA can be encountered unexpectedly during dermatologic surgery. An aneurysm is a type of VA and is defined as an abnormal dilatation of a blood vessel that can be arterial, venous, or an arteriovenous malformation. Most reported aneurysms of the head and neck are cirsoid aneurysms or involve the superficial temporal artery.^2,3 Reports of superficial venous aneurysms are rare.⁴ Preoperatively, cutaneous nodules can be evaluated for findings suggestive of a VA in the dermatologist’s office through physical examination. Arterial aneurysms may reveal palpable pulsation and audible bruit, while a venous aneurysm may exhibit a blue color, a size reduction with compression, and variable size with Valsalva maneuver.

The gold standard diagnostic tool for most dermatologic conditions is histopathology; however, dermatologic ultrasonography can provide noninvasive, real-time, important diagnostic characteristics of cutaneous pathologies as well as VA.^5-7 Crisan et al⁶ outlined specific sonographic findings of lipomas, EICs, trichilemmal cysts, and other dermatologic conditions as well as the associated surgical pertinence. Ultrasonography of a venous aneurysm may show a heterogeneous, contiguous, echoic lesion with an adjacent superficial vein, which may be easily compressed by the probe.⁸ Advanced imaging such as computed tomography with contrast or magnetic resonance imaging may be performed, but these are more costly than ultrasonography. Additionally, point-of-care ultrasonography is becoming more popular and accessible for physicians to carry at bedside with portable tablet options available. Dermatologists may want to consider incorporating it into the outpatient setting to improve procedural planning.⁹

In conclusion, VAs should be included in the differential diagnosis of soft cutaneous nodules, as management differs from a cyst or lipoma. Dermatologists should use their clinical judgment preoperatively—including a comprehensive history, physical examination, and consideration of color Doppler ultrasonography to assess for findings of VA. We do not recommend intentional surgical exploration of cutaneous aneurysms in the ambulatory setting due to risk for hemorrhage. Furthermore, when clinical suspicion of EIC or lipoma is high, it still is preferable to descend the incision slowly at 1 to 2 mm per cut until the tumor is visualized.

To the Editor:

Cutaneous cysts commonly are treated by dermatologists and typically are diagnosed clinically, followed by intraoperative or histologic confirmation; however, cyst mimickers can be misdiagnosed due to similar appearance and limited diagnostic guidelines.¹ Vascular anomalies (VAs) of the face such as a facial aneurysm are rare.² Preoperative assessment of findings suggestive of vascular etiology vs other common cutaneous tumors such as an epidermal inclusion cyst (EIC) and lipoma can help guide dermatologic management. We present a case of a VA of the glabella manifesting as a flesh-colored nodule that clinically mimicked a cyst and discuss the subsequent surgical management.

A 61-year-old man with a history of benign prostatic hyperplasia was evaluated at our dermatology clinic for an enlarging forehead mass of 1 year’s duration. Physical examination yielded a soft, flesh-colored, 2.5-cm nodule located superficially in the midline glabellar region without pulsation or palpable thrill. The differential diagnosis at the time included lipoma or EIC.

Excision of the lesion was performed utilizing superficial incisions with a descending depth of 1-mm increments to safely reach the target, identify the type of tumor, and prevent rupture of the suspected EIC. After the third incision to the level of the dermis, nonpulsatile bleeding was more than expected for a cyst. Digital pressure was applied, and the area was explored with blunt dissection to identify the source of bleeding. A fusiform, thin-walled aneurysm was identified in the dermal plane with additional tributaries coursing deep into the subcutaneous plane. The visualized tributaries were ligated with 3-0 polyglactin, figure-of-eight sutures resulting in hemostasis. The wound was closed with 5-0 nylon simple interrupted sutures. The patient was closely followed postoperatively for 1 week (Figure) and was referred for head imaging to evaluate for a possible associated intracranial aneurysm. Based on the thin vessel wall and continuous nonpulsatile hemorrhage, this VA was most consistent with venous aneurysm.

A VA can be encountered unexpectedly during dermatologic surgery. An aneurysm is a type of VA and is defined as an abnormal dilatation of a blood vessel that can be arterial, venous, or an arteriovenous malformation. Most reported aneurysms of the head and neck are cirsoid aneurysms or involve the superficial temporal artery.^2,3 Reports of superficial venous aneurysms are rare.⁴ Preoperatively, cutaneous nodules can be evaluated for findings suggestive of a VA in the dermatologist’s office through physical examination. Arterial aneurysms may reveal palpable pulsation and audible bruit, while a venous aneurysm may exhibit a blue color, a size reduction with compression, and variable size with Valsalva maneuver.

The gold standard diagnostic tool for most dermatologic conditions is histopathology; however, dermatologic ultrasonography can provide noninvasive, real-time, important diagnostic characteristics of cutaneous pathologies as well as VA.^5-7 Crisan et al⁶ outlined specific sonographic findings of lipomas, EICs, trichilemmal cysts, and other dermatologic conditions as well as the associated surgical pertinence. Ultrasonography of a venous aneurysm may show a heterogeneous, contiguous, echoic lesion with an adjacent superficial vein, which may be easily compressed by the probe.⁸ Advanced imaging such as computed tomography with contrast or magnetic resonance imaging may be performed, but these are more costly than ultrasonography. Additionally, point-of-care ultrasonography is becoming more popular and accessible for physicians to carry at bedside with portable tablet options available. Dermatologists may want to consider incorporating it into the outpatient setting to improve procedural planning.⁹

In conclusion, VAs should be included in the differential diagnosis of soft cutaneous nodules, as management differs from a cyst or lipoma. Dermatologists should use their clinical judgment preoperatively—including a comprehensive history, physical examination, and consideration of color Doppler ultrasonography to assess for findings of VA. We do not recommend intentional surgical exploration of cutaneous aneurysms in the ambulatory setting due to risk for hemorrhage. Furthermore, when clinical suspicion of EIC or lipoma is high, it still is preferable to descend the incision slowly at 1 to 2 mm per cut until the tumor is visualized.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The efficacy of clascoterone cream 1% for treating acne vulgaris appears to increase over time after 12 weeks of use and up to 1 year.

METHODOLOGY:

• A 1% cream formulation of clascoterone, a topical androgen receptor inhibitor, is approved for the treatment of acne vulgaris in patients aged 12 years and older based on results from two identical phase 3 12-week trials, NCT02608450 and NCT02608476, and a long-term extension (LTE) study.
• The purpose of the current study was to evaluate the integrated efficacy of clascoterone cream 1% (Winlevi) in the intention-to-treat population of patients from all three trials.
• In the pivotal trials, investigators randomized patients with acne 1:1 to receive clascoterone cream 1% or vehicle twice daily for 12 weeks. Participants were eligible to enter the LTE study, in which patients applied clascoterone to the face, and if they wanted to, the trunk for up to 9 more months.
• To assess combined efficacy, researchers evaluated the proportion of patients who achieved an Investigator’s Global Assessment (IGA) of 0 or 1.

TAKEAWAY:

• Of the 1143 patients from the pivotal trials who completed 12 weeks of treatment, 576 were in the clascoterone group and 567 were in the vehicle group. Of the 600 patients who entered the LTE study, 311 were in the clascoterone group and 289 were in the vehicle group. Of these, 343 completed the LTE study.
• At week 12, the proportion of patients who achieved treatment success was higher in the clascoterone group than in the vehicle group (19.9% vs 7.7%, respectively; P < .0001).
• In the LTE study, the proportion of patients previously treated with clascoterone who achieved a facial IGA of 0/1 increased from 13.5% at extension day 0 to 29.9% at extension day 274, while the proportion of patients previously treated with vehicle and switched to clascoterone who achieved a facial IGA of 0/1 increased from 6.2% at extension day 0 to 30.4% at extension day 274.
• Similarly, the proportion of patients in the LTE study with a truncal IGA of 0/1 increased from 4.9% at extension day 0 to 31.7% on extension day 274.

IN PRACTICE:

“Clinicians may consider counseling patients that treatment persistence is required to maximize the efficacy of clascoterone treatment,” the authors concluded.

SOURCE:

Lawrence F. Eichenfield, MD, of the departments of dermatology and pediatrics at the University of California and Rady Children’s Hospital, San Diego, California, led the research. The study was published in the January 2024 issue of the Journal of Drugs in Dermatology.

LIMITATIONS:

There was a high patient discontinuation rate before and during the LET study. Also, no assessment was made as to how clascoterone affected patients’ quality of life.

DISCLOSURES:

Clascoterone manufacturer Cassiopea funded the studies. Dr. Eichenfield and fellow investigators Adelaide A. Hebert, MD, and Linda Stein Gold, MD, received compensation from Cassiopea as advisers and disclosed ties to many other pharmaceutical companies.
 

A version of this article appeared on Medscape.com.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Nearly 10% of survivors of head, neck, esophageal, and gastric cancers experienced active substance use disorders, based on data from more than 6,000 individuals.

The association between cancer and substance use is well known, but data on the prevalence of different substance use disorders (SUDs) in different types of cancer are limited, Katie F. Jones, PhD, of the VA Boston Healthcare System, and colleagues, wrote in their paper.

“Substance use and use disorders are on the rise in general and among older adults, who represent the majority of people diagnosed with cancer, and SUDs have significant potential to complicate cancer care and negatively impact cancer outcomes,” corresponding author Devon K. Check, PhD, of Duke University, Durham, N.C., said in an interview. “We thought it was important to understand whether SUDs are more common with certain types of cancer. We can use that information to guide resources toward populations where interventions to integrate SUD treatment and cancer treatment are most needed,” he said. “In addition, because different SUDs (opioid use disorder, alcohol use disorder) might complicate cancer treatment in different ways and necessitate different types of interventions, we thought it was important to understand the distribution of specific disorders,” he explained.

In the cross-sectional study published in JAMA Oncology, the researchers reviewed data from 6,101 adult cancer survivors who participated in the National Survey of Drug Use and Health (NSDUH) between 2015 and 2020.

The study population included survivors of solid tumor cancers. SUD was defined as meeting at least one of four criteria for substance abuse or at least 3 of 6 criteria for dependence based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria.

Overall, 3.83% of the participants met criteria for SUD. Survivors of head and neck cancers and survivors of gastric and esophageal cancers had the highest rates of SUDs (approximately 9%), followed by cervical cancer and melanoma survivors (approximately 6%).

Alcohol use disorder was the most common SUD both overall (2.8%) and among survivors of head and neck cancers, cervical cancers, and melanoma.

Cannabis use disorder was the most prevalent SUD among esophageal and gastric cancer survivors (approximately 9%).

The prevalence of SUDs overall and within the past year (active) was approximately 4%, but the prevalence of active SUDs was significantly higher for those with head and neck cancers and cervical cancer (18.73% and 15.70%, respectively). However, the distribution of specific SUDs was different in the newly diagnosed patients. Sedative use disorder took the top spot as the most common SUD for head and neck cancer survivors (9.81%), while alcohol use disorder was the most common SUD among cervical cancer survivors (10.49%).
 

Limitations and Implications

The findings were limited by several factors, including the nature of the study population and the data source, said Dr. Check.

“The average prevalence of SUD (or the prevalence across cancer types) was lower than we might have expected,” but the results make sense given the mainly older and female study population, he said. SUDs are less common among older adults compared with younger adults and among women compared with men, and the study’s data source (NSDUH) has been shown in other research to underestimate the prevalence of opioid use disorder, he added.

“Otherwise, the study findings were generally consistent with what we would expect,” Dr. Check said in an interview. “For example, alcohol use disorder is the most common SUD in the general U.S. population, and that was true for our study population of cancer survivors as well. In addition, SUD prevalence was higher in cancers such as cervical cancer and head and neck cancers that are causally linked to alcohol and/or tobacco use,” he said.
 

Integrated care is needed

“Among people diagnosed with certain types of cancers, including cervical and head and neck cancers, the estimated prevalence of SUD is similar to those [with] medical comorbidities such as diabetes and cardiopulmonary conditions,” said Dr. Check. “Within the field, there is an increasing emphasis on ensuring that people diagnosed with cancer have access to integrated care for their comorbid medical conditions. Similar efforts for people who concurrently manage cancer and SUD are largely absent but critically needed; these efforts should prioritize cancer populations where SUD prevalence is high,” he said.

Looking ahead, “We need to understand more about the specific challenges that arise at the intersection of cancer and SUD so we can design interventions and programs to better support both patients who concurrently manage cancer and SUD and the clinicians who care for them,” Dr. Check added.
 

Recognize risk factors

“It is very important to study overall substance use disorders in patients with cancer, because understanding the risks of developing these issues after treatment helps us develop approaches to best support these patients following their cancer therapies,” Henry S. Park, MD, a radiation oncologist at Yale University, New Haven, Connecticut, said in an interview.

The current study findings “are generally consistent with my experience and intuition, but it is still helpful to see the actual data,” said Dr. Park, who was not involved in the study. “This may be partially because of the baseline elevated risk of preexisting SUDs for certain patients from the higher-prevalence disease sites. However, it may also be related to the intense side effects that survivors of some types of cancers, such as head and neck cancer, gastroesophageal cancer, and cervical cancer, may experience soon after treatment, and even chronically long after treatment,” he said.
 

Individualize risk assessment

“Ultimately, clinicians should be aware that not all patients with cancer are the same, and that the majority do not necessarily develop SUDs,” Dr. Park said in an interview. “We should be careful to treat symptoms appropriately, and not withhold therapies purely because of an elevated risk of developing SUDs. However, there are some patients who are at higher risk of SUDs who will need extra support and care from physicians, advanced practice providers, nutritionists, social workers, psychologists, dietitians, and survivorship clinics, both in the short-term and long-term,” he emphasized.

As for additional research, “more work needs to be done on which particular patients within each disease subset are most likely to develop SUDs,” said Dr. Park. “Most importantly, once we identify our high-risk group as reliably as possible, we will have to study interventions that rely on supporting and partnering with patients to decrease the risk of developing SUDs as much as possible, while adequately treating residual symptoms and quality-of-life effects following cancer treatment,” he said.

The study received no outside funding. Dr. Check disclosed grants from Duke University during the study period and grants from the National Institutes of Health and AstraZeneca unrelated to the current study. Dr. Park had no financial conflicts to disclose.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

About 60% of US physicians who served as panel and task force members for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR) received more than $14 million in undisclosed industry funding, a new study shows. 

Most payments were for food and beverages, travel, and consulting fees. But more than one third of contributors received compensation for services other than consulting, such as serving on a pharmaceutical company’s speakers bureau, which medical ethicists say is particularly problematic. 

Often referred to as the bible of psychiatric disorders, the DSM-5-TR was released in 2022 by the American Psychiatric Association (APA) and includes changes that were made online since the DSM-5 was first published in 2013.

An APA spokesperson said that DSM-5-TR decision-makers were unable to participate if they had received more than $5000 in industry payments and that all 186 individuals who worked on the text revision were required to disclose all sources of income prior to their participation. 

“The APA implemented and enforced a rigorous process for DSM-5-TR that required transparency by all contributors of their personal and professional interests, followed by an independent review to ensure that personal and professional interests did not bias any results,” the spokesperson said.

However, having industry funding did not preclude contributors’ participation, and investigators note that none of the disclosures were published in the manual or shared publicly. 

“The point is not to point fingers at the APA or individual members of the APA but rather to provide hopefully a small piece of research data that would help the APA look at the larger systemic issue of conflicts of interest,” said the study’s lead investigator Lisa Cosgrove, PhD, professor of counseling and faculty fellow in the Applied Ethics Center at the University of Massachusetts Boston. 

The findings were published online in The BMJ .

A Deep Dive

The work builds on the investigators’ earlier research into financial conflicts among DSM contributors. The lack of a centralized database of industry payments made the group›s prior studies far more complicated and time-consuming. 

For this project, investigators drew on the Open Payments database, which launched in 2014. It collects and publishes data on payments by pharmaceutical and medical device companies to physicians and other healthcare professionals for research, meals, travel, gifts, speaking fees, and other expenses. The program was established as part of the Affordable Care Act and is run by the Centers for Medicare & Medicaid Services. 

Investigators analyzed industry payments made to DSM-5-TR contributors between 2016 and 2019, just before work on the text revision began. Of the 168 individuals listed as contributors to the manual, 92 met the inclusion criteria of being a US-based physician with industry payments tracked in Open Payments.

Fifty-five of those physicians, or 59.8%, had financial ties to industry. The most common type of payment was for food and beverages (90.9%), travel (69.1%), and consulting (69.1%). Nineteen panel members received $1.8 million for “compensation for services other than consulting, including serving as faculty or as a speaker at a venue other than a continuing education program.”

The greatest proportion of compensation by category of payment was for research funding (71%).

Investigators found that every DSM-5-TR panel included at least one member with industry ties. The panels with the highest number of members with a recent history of industry funding were those for neurodevelopmental disorders; bipolar disorders; obsessive-compulsive disorders; neurocognitive disorders; medication induced movement disorders; and disruptive, impulse control, and conduct disorders. More than 70% of members on those panels had received industry funding. 

The total payments received by all contributors was more than $14.2 million, with a range from just under $14 per physician to $2.7 million per physician. The researchers note that the percentage of panel members with industry support was similar between DSM-5-TR and DSM-5.

“What we also see that’s consistent with our 2016 study and 2012 study is the panels for which the members had the most financial ties to industry were those for which pharmaceutical interventions are the first line of therapy,” Dr. Cosgrove said.

No Public Disclosure

For DSM-5, the APA instituted a new disclosure policy for contributors and reported those disclosures on its website. 

This time, the association spokesperson said that DSM-5-TR chairs and the DSM Steering Committee who reviewed all proposed changes were required to have no industry-related income above $5000 and that “in fact, many had no industry income.”

Other DSM-5-TR contributors had to submit “extensive” disclosure forms and report “any relationships they or close relations had with industry (very broadly defined) and sources of income,” the spokesperson added. They were also asked to report other nonfinancial interests that they or close relatives had that could potentially bias their work. 

The APA’s standing Conflict of Interest Committee reviewed all disclosure forms and flagged those with disclosures that could impact content. Text written by individuals with flagged disclosures received additional review, the spokesperson said. 

“If any possible bias was noted in the text content, such as for a potential commercial advantage with a diagnostic instrument, that content was deleted,” the spokesperson said.

However, the real sticking point for medical ethicists is that unlike with the DSM-5, the APA did not share DSM-5-TR contributors’ disclosures publicly. 

Commenting on the research, Bernard Lo, MD, professor emeritus of medicine and director emeritus of the Program in Medical Ethics Emeritus at University of California, San Francisco, said that the lack of public disclosure is critical.

“Part of the report should be, ‘Here are the conflicts of interest reported by the members of the panel,’” said Dr. Lo, adding that publishing disclosures is standard in all of APA’s peer-reviewed journals. “Failure to do that in the DSM-5-TR is unacceptable from an ethical and transparency point of view.”

Loss of Public Trust?

In her previous research and in this new study, Dr. Cosgrove recommends the APA follow the 2011 report Clinical Practice Guidelines We Can Trust. Published by the Institute of Medicine (IOM, now called the National Academy of Medicine), that report updated and streamlined a 2009 conflicts of interest guideline, which Dr. Lo coauthored. 

“The IOM recommends that the whole guideline development group be free of industry ties,” Dr. Cosgrove said. “At a minimum, the chair should not have ties and the majority of folks should not have ties to industry.”

Some have argued that banning all contributors with industry ties would shrink the expert pool that develops the DSM and other guidelines. Dr. Cosgrove disagrees with that assertion.

“There are hundreds of experts in all medical disciplines that do not have industry ties,” Dr. Cosgrove said. “The ‘most experts have industry ties’ is a spurious and unsupported argument.”

The APA also should ban contributors who receive industry funding as key opinion leaders, known as KOLs, such as members of pharmaceutical companies’ speakers bureaus, Dr. Lo said. 

“Certain types of funding relationships with industry are more fraught with ethical problems,” including KOLs, who Dr. Lo said are “basically salespeople trying to increase sales of a product.” 

“It really compromises their scientific objectivity and should exclude someone from any practice guideline body,” Dr. Lo said. “This failure to adequately address conflicts of interest doesn’t promote transparency and it doesn’t promote public trust in the diagnostic criteria.”

The Larger Issue

Removing financial conflicts of interest is a start, but it wouldn’t address the larger issue in medicine, said Allen Frances, MD, who chaired the DSM-4 task force and has been an outspoken critic of the DSM-5. 

“The financial conflicts of interest may play a role with some people, I’m not denying that,” said Dr. Frances, a professor and chair emeritus of psychiatry at Duke University, Durham, North Carolina. “But that’s a much smaller problem than the fact that any individual from any professional association that has an intense interest in any given diagnosis will always be on the side of expanding that diagnosis and expanding the treatment for it.”

Though financial conflicts of interest can be addressed, Frances believes that professionals’ “intellectual and emotional conflicts” are much harder to overcome. 

“People who spend their careers working on any diagnosis are terribly biased by virtue of their attachment to their work,” he said. 

The solution is for guidelines in psychiatry and all medical fields to be developed by a truly multidisciplinary “neutral board” that includes broad representation of primary care physicians. 

Specialists would be involved in the development of the guidelines but would not have a final say in what diagnoses or treatments are included or excluded. 

“80% of psychiatric meds are prescribed by primary care doctors, not psychiatrists,” he said. “So, when you’re making a suggestion for a change in psychiatry, you’re making that suggestion primarily for primary care doctor and have to be thinking about, How will this change play in primary care, which the experts never do.”

The study was unfunded. Dr. Allen reported no relevant disclosures. Dr. Lo served as a paid member of the Takeda Pharmaceuticals Ethics Advisory Committee.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.

Exposure to endocrine-disrupting chemicals (EDCs) via daily use of plastics is a major contributor to the overall disease burden in the United States and the associated costs to society amount to more than 1% of the gross domestic product, revealed a large-scale analysis.

The research, published in the Journal of the Endocrine Society, indicated that taken together, the disease burden attributable to EDCs used in the manufacture of plastics added up to almost $250 billion in 2018 alone.

“The diseases due to plastics run the entire life course from preterm birth to obesity, heart disease, and cancers,” commented lead author Leonardo Trasande, MD, MPP, Jim G. Hendrick, MD Professor of Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, in a release.

“Our study drives home the need to address chemicals used in plastic materials” through global treaties and other policy initiatives, he said, so as to “reduce these costs” in line with reductions in exposure to the chemicals.

Co-author Michael Belliveau, Executive Director at Defend Our Health in Portland, ME, agreed, saying: “We can reduce these health costs and the prevalence of chronic endocrine diseases such as diabetes and obesity if governments and companies enact policies that minimize exposure to EDCs to protect public health and the environment.”

Plastics may contain any one of a number of EDCs, such as polybrominated diphenylethers in flame retardant additives, phthalates in food packaging, bisphenols in can linings, and perfluoroalkyl and polyfluoroalkyl substances (PFAS) in nonstick cooking utensils.

These chemicals have been shown to leach and disturb the body’s hormone systems, increasing the risk for cancer, diabetes, reproductive disorders, neurological impairments in developing fetuses and children, and even death.

In March 2022, the United Nations Environment Assembly committed to a global plastics treaty to “end plastic pollution and forge an international legally binding agreement by 2024” that “addresses the full life cycle of plastic, including its production, design and disposal.”

Minimizing EDC Exposure

But what can doctors tell their patients today to help them reduce their exposure to EDCs?

“There are safe and simple steps that people can take to limit their exposure to the chemicals of greatest concern,” Dr. Trasande told this news organization.

This can be partly achieved by reducing plastic use down to its essentials. “To use an example, when you are flying, fill up a stainless steel container after clearing security. At home, use glass or stainless steel” rather than plastic bottles or containers.

In particular, “avoiding microwaving plastic is important,” Dr. Trasande said, “even if a container says it’s microwave-safe.”

He warned that “many chemicals used in plastic are not covalently bound, and heat facilitates leaching into food. Microscopic contaminants can also get into food when you microwave plastic.”

Dr. Trasande also suggests limiting canned food consumption and avoiding cleaning plastic food containers in machine dishwashers.

Calculating the Disease Burden

To accurately assess the “the tradeoffs involved in the ongoing reliance on plastic production as a source of economic productivity,” the current researchers calculated the attributable disease burden and cost related to EDCs used in plastic materials in the United States in 2018.

Building on previously published analyses, they used industry reports, publications by national and international governing bodies, and peer-reviewed publications to determine the usage of each type of EDC and its attributable disease and disability burden.

This plastic-related fraction (PRF) of disease burden was then used to calculate an updated cost estimate for each EDC, based on the assumption that the disease burden is directly proportional to its exposure.

They found that for bisphenol A, 97.5% of its use, and therefore its estimated PRF of disease burden, was related to the manufacture of plastics, while this figure was 98%-100% for phthalates. For PDBE, 98% of its use was in plastics vs 93% for PFAS.

The researchers then estimated that the total plastic-attributable disease burden in the United States in 2018 cost the nation $249 billion, or 1.22% of the gross domestic product. Of this, $159 billion was linked to PDBE exposure, which is associated with diseases such as cancer.

Moreover, $1.02 billion plastic-attributable disease burden was associated with bisphenol A exposure, which can have potentially harmful health effects on the immune system; followed by $66.7 billion due to phthalates, which are linked to preterm birth, reduced sperm count, and childhood obesity; and $22.4 billion due to PFAS, which are associated with kidney failure and gestational diabetes.

The study was supported by the National Institutes of Health and the Passport Foundation.

Dr. Trasande declared relationships with Audible, Houghton Mifflin, Paidos, and Kobunsha, none of which relate to the present manuscript.

No other financial relationships were declared.

A version of this article appeared on Medscape.com.