This story republished by permission of ProPublica.

Hundreds of doctors packed an auditorium at Memorial Sloan Kettering Cancer Center on Oct. 1, deeply angered by revelations that the hospital’s top medical officer and other leaders had cultivated lucrative relationships with for-profit companies.

One by one, they stood up to challenge the stewardship of their beloved institution, often to emotional applause. Some speakers accused their leaders of letting the quest to make more money undermine the hospital’s mission. Others bemoaned a rigid, hierarchical management that had left them feeling they had no real voice in the hospital’s direction.

“Slowly, I’ve seen more and more of the higher-up meetings happening with people who are dressed up in suits as opposed to white coats,” said Viviane Tabar, MD, chairwoman of the neurosurgery department.

“The corporatization of this institution is clear to many of us who have been here a long time,” said Carol L. Brown, MD, a gynecologic cancer surgeon, according to an audio recording of the meeting.

The meeting ended after several doctors advocated an immediate no-confidence vote in the hospital’s senior leadership. The turmoil followed reports by The New York Times and ProPublica that the hospital’s chief medical officer, José Baselga, MD, had been paid millions by drug and health care companies and failed to disclose those ties more than 100 times in medical journals, and that hospital insiders had made lucrative side deals that stood to earn them handsome profits, sometimes for work they had done on the job.

The day after the meeting, the hospital’s chief executive, Craig B. Thompson, MD, promised greater openness with rank-and-file doctors about decisionmaking. He also committed to doing the “root-cause analysis” requested by the doctors of how “egregious conflicts of interest,” as one physician put it, had been allowed to happen.

Other hospitals around the country are confronting similar dilemmas. But at Memorial Sloan Kettering, one of the nation’s leading cancer research and treatment centers, they are especially acute. Internal emails, audio recordings of meetings and interviews with doctors show how this major New York institution has struggled to contain a crisis of confidence in its leadership.

Closer ties between nonprofit research centers like Memorial Sloan Kettering and corporations are being fueled by a rush of potentially breakthrough cancer treatments. Venture capital firms and drug companies have looked to cash in on the scientific discoveries, said Brad Loncar, the founder of an investment fund that focuses on cancer. “Money follows success,” he said, and Memorial Sloan Kettering has been a focus “because they conduct terrific science there.”

In recent years, the hospital, like its competitors, has struck increasingly sophisticated deals to commercialize its discoveries, in some cases receiving equity stakes in startups rather than simply collecting royalties.

The predicament of Memorial Sloan Kettering also reflects a shift in its own culture. Its prior chief executive, Harold E. Varmus, MD, a Nobel Prize-winning scientist, personally kept companies at arm’s length, while Dr. Thompson, also a respected cancer researcher, has more fully embraced such relationships. The new approach has been applauded by some for expanding access to the cancer center’s discoveries, even as others have worried that the hospital may be losing sight of its mission.

Its leaders and top researchers also hold influential positions in the corporate world. When news of Dr. Baselga’s disclosure lapses broke in September, 12 doctors and researchers at the hospital served on the boards of publicly traded companies, more than at any other major cancer center, according to a review by the Times and ProPublica. Dr. Baselga has since resigned from the hospital and the two boards he served on. And a day after the physicians’ meeting on Oct. 1, Dr. Thompson resigned from the boards of the pharmaceutical giant Merck and Charles River Laboratories, a health care company, that together had paid him $585,050 in compensation in 2017.

The concern of ethicists and health experts is that a bias in favor of industry can unduly influence scientific research and medical treatments and remove a valuable check on soaring drug prices.

“We do have to sort of decide which side of this we’re on, or at least notice that we are feeding at the very trough that is causing worse access here than in any other Western country,” Peter B. Bach, MD, director of the hospital’s Center for Health Policy and Outcomes, said at the Oct. 1 meeting.

The problems at Memorial Sloan Kettering have shaken other cancer centers. At Dana-Farber Cancer Institute, officials have said they are considering whether Laurie H. Glimcher, MD, their chief executive, and others should continue to serve on the boards of publicly traded companies, including the drugmaker GlaxoSmithKline, on whose board Dr. Glimcher sits.

At the Fred Hutchinson Cancer Research Center in Seattle, a task force is reviewing the conflict-of-interest policies that govern employees’ financial relationships with drug companies. And medical centers around the country have instructed researchers to review their financial disclosures to medical journals, leading to a series of corrections to scientific articles.

Even as Memorial Sloan Kettering leaders have promised greater transparency, they have engaged a public affairs firm, SKDKnickerbocker, to manage their message and have aggressively pushed back against the idea that the hospital’s leaders are too close to industry.

“I can see how someone might think that business relationships are problematic,” said Lisa DeAngelis, MD, who has stepped into Dr. Baselga’s former position at Memorial Sloan Kettering on an acting basis. “But I’m telling you, as someone who works with patients, and I’ve worked with patients throughout my entire career here, that working with industry has helped me save lives.”

The Times and ProPublica asked to speak to Dr. Tabar and Dr. Brown about the critical remarks they made about the hospital’s direction at the Oct. 1 meeting. Mike Morey, managing director of the communications firm engaged by the hospital, arranged for them to speak to reporters on the phone while he listened. The doctors said they were not specifically referring to Memorial Sloan Kettering during the meeting that was recorded by one of those in attendance, but to broader changes in the medical world.

Defining an Institution’s Role

Founded in 1884 as the New York Cancer Hospital, Memorial Sloan Kettering was the first hospital in the country devoted exclusively to treating cancer. Its benefactors have included some of the wealthiest families in America, from the Astors and Rockefellers in its early years to the Kochs today.

It now operates more than 120 research laboratories, employs more than 1,000 doctors, admits some 23,500 patients a year, operates one of the world’s largest clinical trial programs and had revenues of nearly $4.5 billion in 2017. It recently completed a $3.5 billion fundraising drive, and its charity ball remains a fixture on New York’s social calendar.

As a leading force in cancer research, the hospital has long grappled with striking a balance in its collaborations with drug companies. While it did business with industry during the tenure of Dr. Varmus, a former director of the National Institutes of Health, he and a top deputy, Robert E. Wittes, MD, did not consult for companies, own their stock or serve on their boards, according to several people who worked for Dr. Varmus while he was at the hospital from 2000 to 2010. Dr. Varmus and Dr. Wittes declined to comment.

But some on the hospital’s board wanted its chief executive to do more to encourage company-financed clinical trials and to bring discoveries to market. In an interview, John R. Gunn, the cancer center’s chief operating officer from 1987 to 2015, said board members felt gems of research were “lying fallow and nobody was kind of pushing it, to commercialize it.”

By the time Dr. Varmus left to direct the National Cancer Institute in 2010, Memorial Sloan Kettering’s board was looking for a leader who was as comfortable in a corporate boardroom as in the lab, according to several longtime current and former cancer center employees.

Dr. Thompson met that criteria. He headed the Abramson Cancer Center at the University of Pennsylvania, was the co-founder of a biotech startup, Agios, and served on the board of Merck.

His early tenure was marred by controversy. In 2011 and 2012, he was sued by his former employers, the Abramson center and the University of Pennsylvania, which accused him of walking off with valuable research and using it to start Agios. At the time, Dr. Thompson denied wrongdoing and the suits were later settled for an undisclosed sum.

In 2012, Dr. Thompson hired Dr. Baselga to be the top physician at Memorial Sloan Kettering. Dr. Baselga, who had made his name as a key investigator of the breast cancer drug Herceptin, was also seen as having bridged the worlds of research and industry. Dr. DeAngelis, the hospital’s acting physician-in-chief, said that under Dr. Baselga, clinical trials were approved more quickly, helping speed treatments to patients.

But several doctors who worked under Dr. Baselga said in interviews that he had an abrasive style and created a culture where ties to industry were not kept in check. Dr. Baselga has not responded to requests for comment.

In his years at Memorial Sloan Kettering, Dr. Baselga’s personal financial conflicts were handled differently from those of other doctors, according to Clifford A. Hudis, MD, who was chairman of the hospital’s conflict-of-interest advisory committee through early 2016, when he left to become chief executive of the American Society of Clinical Oncology.

Dr. Baselga’s conflicts were not overseen by Dr. Hudis’ committee, but by the audit committee of the hospital’s board of directors. “I was told this was pretty standard for the highest level executives,” Dr. Hudis said. “I didn’t understand why any clinician would have separate rules from any other.”

Mr. Morey said that the hospital is evaluating its process for reviewing conflicts of interest, but that executives like Dr. Baselga had their financial relationships overseen by the board “to protect faculty from being put in a position of having to review their supervisor’s potential conflicts.”

Dr. Baselga is not the only leading researcher to have maintained extensive ties to the drug and health care companies — as some also did under Dr. Varmus. Jedd Wolchok, MD, a noted pioneer in immunotherapy, has financial relationships with more than 30 companies, according to recent disclosures. Charles L. Sawyers, MD, another of the hospital’s biggest names, has founded several cancer startups, one of which Memorial Sloan Kettering has invested in, and serves on the board of the Swiss pharmaceutical giant Novartis.

Ethicists and health experts say having leaders and researchers at nonprofit hospitals sit on corporate boards is especially problematic. When they serve on the board of a publicly traded company, they have a legal duty to the corporation and its shareholders, which can clash with their duty to their patients and primary employers. Those who sit on boards are often paid hundreds of thousands of dollars a year.

“I don’t think you can serve two masters,” said Bernard Lo, MD, who led an influential Institute of Medicine panel in 2009 that investigated financial conflicts in medicine. “The whole reason for being in the cancer care business is that you’re trying to help people in need, and that’s not at all the company’s main purpose. It’s to generate profits on their products.”

A report in November in BioPharma Dive found that 12 of the 19 largest pharmaceutical and biotech companies had at least one board member who also worked at a nonprofit health care institution. A 2014 study in JAMA found that about 40 percent of the largest publicly traded drug companies had a leader of an academic medical center on their boards.

Robert Benezra, PhD, who heads a lab at Memorial Sloan Kettering that focuses on how tumors grow, is the president, chief executive officer and a board member of AngioGenex, a tiny, publicly traded biotech company that is developing drugs to treat cancer based on the discoveries made in his lab.

Though he takes no salary from AngioGenex, Benezra owns nearly 9 percent of the company he helped found through stock or options, setting him up for a lucrative payday if the company is acquired or its drugs come to market.

In 2017, Dr. Benezra wrote to AngioGenex shareholders that a recent policy and leadership change at the hospital “afforded me the freedom to assume a more active role in the company” and to recruit other Memorial Sloan Kettering scientists to work with the company.

Dr. Benezra said in a statement issued through the hospital, “While I do not work directly with patients, I hope that this important science can one day make an impact in the lives of cancer sufferers.”

Mr. Morey said Dr. Benezra spends just 30 hours a year on business related to the publicly traded company. “We’re talking about 45 minutes a week, which is less than what most people spend on Netflix in a night,” Mr. Morey said.

Dr. DeAngelis, the acting physician-in-chief, said the high number of Memorial Sloan Kettering leaders who serve on corporate boards is reflective of their stature. “Maybe we should turn this around and say, we have more people on corporate boards because people value the opinions from our faculty,” she said in an interview.
 

A Staff in Turmoil

Tensions among doctors at the hospital over conflicts of interests mounted through September. On Sept. 28, Colin Begg, PhD, the chairman of its department of epidemiology and biostatistics, wrote to other department heads. “The key substantive issue is that the problems we face were not caused by failures to disclose conflicts. The problems were due to the conflicts themselves,” he wrote in the email, a copy of which was obtained by the Times and ProPublica.

Referring to Dr. Thompson and Douglas A. Warner III, the outgoing chairman of the hospital’s board of managers and overseers, who is known as Sandy, he said: “As far as I can tell neither Sandy nor Craig understand this very basic point. And if you don’t recognize that a problem exists there is no chance you will solve it.”

He also said: “Making billions is not our mission. MSK is a nonprofit with a fundamentally social mission.”

Dr. Begg declined to comment.

Shortly before the doctors met on Oct. 1, Dr. Thompson sounded a conciliatory note. “I want to start by apologizing to the medical staff on behalf of myself and the rest of senior management,” he said, according to a draft transcript of the staff meeting. “The events of the last few weeks have not been handled as well as I would have liked.”

Mr. Warner also addressed the doctors, informing them that the board was assessing whether Dr. Thompson should remain on Merck’s board.

“Should Craig continue to sit on the Merck board? We have no policy on that,” Mr. Warner said, according to the transcript, noting that Dr. Thompson’s role on the board was initially seen as a “good thing” when he joined the hospital. “We need to step back from that now and ask ourselves whether that continues to be appropriate, whether it’s appropriate in the future.”

The next day, Oct. 2, Dr. Thompson announced that he was resigning from both the boards on which he served.

Requests to interview Dr. Thompson and Mr. Warner were declined. Instead, the hospital arranged for reporters to speak to Dr. DeAngelis, who said she saw nothing wrong with the corporate ties that Dr. Thompson had earlier said were under review.

She downplayed the concerns voiced by Dr. Begg about the culture of the hospital. ”He is a biostatistician. He does not work with patients. He works with data,” she said, adding that he does not have “as full an understanding” about policies to prevent doctors with corporate ties from having an undue influence on clinical trials.

Dr. Thompson and two deputies, including Dr. DeAngelis, sent a note to hospital doctors on Dec. 20, warning them about this article. While it mentioned the ongoing review, it offered a full-throated defense of those serving on corporate boards.

“We expect the piece to question the ethics of some of our most accomplished researchers and clinicians. We want you to know that we reject these insinuations and we stand behind our faculty 100 percent.”
 

Katie Thomas covers the pharmaceutical industry for The New York Times.

This story republished by permission of ProPublica.

Hundreds of doctors packed an auditorium at Memorial Sloan Kettering Cancer Center on Oct. 1, deeply angered by revelations that the hospital’s top medical officer and other leaders had cultivated lucrative relationships with for-profit companies.

One by one, they stood up to challenge the stewardship of their beloved institution, often to emotional applause. Some speakers accused their leaders of letting the quest to make more money undermine the hospital’s mission. Others bemoaned a rigid, hierarchical management that had left them feeling they had no real voice in the hospital’s direction.

“Slowly, I’ve seen more and more of the higher-up meetings happening with people who are dressed up in suits as opposed to white coats,” said Viviane Tabar, MD, chairwoman of the neurosurgery department.

“The corporatization of this institution is clear to many of us who have been here a long time,” said Carol L. Brown, MD, a gynecologic cancer surgeon, according to an audio recording of the meeting.

The meeting ended after several doctors advocated an immediate no-confidence vote in the hospital’s senior leadership. The turmoil followed reports by The New York Times and ProPublica that the hospital’s chief medical officer, José Baselga, MD, had been paid millions by drug and health care companies and failed to disclose those ties more than 100 times in medical journals, and that hospital insiders had made lucrative side deals that stood to earn them handsome profits, sometimes for work they had done on the job.

The day after the meeting, the hospital’s chief executive, Craig B. Thompson, MD, promised greater openness with rank-and-file doctors about decisionmaking. He also committed to doing the “root-cause analysis” requested by the doctors of how “egregious conflicts of interest,” as one physician put it, had been allowed to happen.

Other hospitals around the country are confronting similar dilemmas. But at Memorial Sloan Kettering, one of the nation’s leading cancer research and treatment centers, they are especially acute. Internal emails, audio recordings of meetings and interviews with doctors show how this major New York institution has struggled to contain a crisis of confidence in its leadership.

Closer ties between nonprofit research centers like Memorial Sloan Kettering and corporations are being fueled by a rush of potentially breakthrough cancer treatments. Venture capital firms and drug companies have looked to cash in on the scientific discoveries, said Brad Loncar, the founder of an investment fund that focuses on cancer. “Money follows success,” he said, and Memorial Sloan Kettering has been a focus “because they conduct terrific science there.”

In recent years, the hospital, like its competitors, has struck increasingly sophisticated deals to commercialize its discoveries, in some cases receiving equity stakes in startups rather than simply collecting royalties.

The predicament of Memorial Sloan Kettering also reflects a shift in its own culture. Its prior chief executive, Harold E. Varmus, MD, a Nobel Prize-winning scientist, personally kept companies at arm’s length, while Dr. Thompson, also a respected cancer researcher, has more fully embraced such relationships. The new approach has been applauded by some for expanding access to the cancer center’s discoveries, even as others have worried that the hospital may be losing sight of its mission.

Its leaders and top researchers also hold influential positions in the corporate world. When news of Dr. Baselga’s disclosure lapses broke in September, 12 doctors and researchers at the hospital served on the boards of publicly traded companies, more than at any other major cancer center, according to a review by the Times and ProPublica. Dr. Baselga has since resigned from the hospital and the two boards he served on. And a day after the physicians’ meeting on Oct. 1, Dr. Thompson resigned from the boards of the pharmaceutical giant Merck and Charles River Laboratories, a health care company, that together had paid him $585,050 in compensation in 2017.

The concern of ethicists and health experts is that a bias in favor of industry can unduly influence scientific research and medical treatments and remove a valuable check on soaring drug prices.

“We do have to sort of decide which side of this we’re on, or at least notice that we are feeding at the very trough that is causing worse access here than in any other Western country,” Peter B. Bach, MD, director of the hospital’s Center for Health Policy and Outcomes, said at the Oct. 1 meeting.

The problems at Memorial Sloan Kettering have shaken other cancer centers. At Dana-Farber Cancer Institute, officials have said they are considering whether Laurie H. Glimcher, MD, their chief executive, and others should continue to serve on the boards of publicly traded companies, including the drugmaker GlaxoSmithKline, on whose board Dr. Glimcher sits.

At the Fred Hutchinson Cancer Research Center in Seattle, a task force is reviewing the conflict-of-interest policies that govern employees’ financial relationships with drug companies. And medical centers around the country have instructed researchers to review their financial disclosures to medical journals, leading to a series of corrections to scientific articles.

Even as Memorial Sloan Kettering leaders have promised greater transparency, they have engaged a public affairs firm, SKDKnickerbocker, to manage their message and have aggressively pushed back against the idea that the hospital’s leaders are too close to industry.

“I can see how someone might think that business relationships are problematic,” said Lisa DeAngelis, MD, who has stepped into Dr. Baselga’s former position at Memorial Sloan Kettering on an acting basis. “But I’m telling you, as someone who works with patients, and I’ve worked with patients throughout my entire career here, that working with industry has helped me save lives.”

The Times and ProPublica asked to speak to Dr. Tabar and Dr. Brown about the critical remarks they made about the hospital’s direction at the Oct. 1 meeting. Mike Morey, managing director of the communications firm engaged by the hospital, arranged for them to speak to reporters on the phone while he listened. The doctors said they were not specifically referring to Memorial Sloan Kettering during the meeting that was recorded by one of those in attendance, but to broader changes in the medical world.

Defining an Institution’s Role

Founded in 1884 as the New York Cancer Hospital, Memorial Sloan Kettering was the first hospital in the country devoted exclusively to treating cancer. Its benefactors have included some of the wealthiest families in America, from the Astors and Rockefellers in its early years to the Kochs today.

It now operates more than 120 research laboratories, employs more than 1,000 doctors, admits some 23,500 patients a year, operates one of the world’s largest clinical trial programs and had revenues of nearly $4.5 billion in 2017. It recently completed a $3.5 billion fundraising drive, and its charity ball remains a fixture on New York’s social calendar.

As a leading force in cancer research, the hospital has long grappled with striking a balance in its collaborations with drug companies. While it did business with industry during the tenure of Dr. Varmus, a former director of the National Institutes of Health, he and a top deputy, Robert E. Wittes, MD, did not consult for companies, own their stock or serve on their boards, according to several people who worked for Dr. Varmus while he was at the hospital from 2000 to 2010. Dr. Varmus and Dr. Wittes declined to comment.

But some on the hospital’s board wanted its chief executive to do more to encourage company-financed clinical trials and to bring discoveries to market. In an interview, John R. Gunn, the cancer center’s chief operating officer from 1987 to 2015, said board members felt gems of research were “lying fallow and nobody was kind of pushing it, to commercialize it.”

By the time Dr. Varmus left to direct the National Cancer Institute in 2010, Memorial Sloan Kettering’s board was looking for a leader who was as comfortable in a corporate boardroom as in the lab, according to several longtime current and former cancer center employees.

Dr. Thompson met that criteria. He headed the Abramson Cancer Center at the University of Pennsylvania, was the co-founder of a biotech startup, Agios, and served on the board of Merck.

His early tenure was marred by controversy. In 2011 and 2012, he was sued by his former employers, the Abramson center and the University of Pennsylvania, which accused him of walking off with valuable research and using it to start Agios. At the time, Dr. Thompson denied wrongdoing and the suits were later settled for an undisclosed sum.

In 2012, Dr. Thompson hired Dr. Baselga to be the top physician at Memorial Sloan Kettering. Dr. Baselga, who had made his name as a key investigator of the breast cancer drug Herceptin, was also seen as having bridged the worlds of research and industry. Dr. DeAngelis, the hospital’s acting physician-in-chief, said that under Dr. Baselga, clinical trials were approved more quickly, helping speed treatments to patients.

But several doctors who worked under Dr. Baselga said in interviews that he had an abrasive style and created a culture where ties to industry were not kept in check. Dr. Baselga has not responded to requests for comment.

In his years at Memorial Sloan Kettering, Dr. Baselga’s personal financial conflicts were handled differently from those of other doctors, according to Clifford A. Hudis, MD, who was chairman of the hospital’s conflict-of-interest advisory committee through early 2016, when he left to become chief executive of the American Society of Clinical Oncology.

Dr. Baselga’s conflicts were not overseen by Dr. Hudis’ committee, but by the audit committee of the hospital’s board of directors. “I was told this was pretty standard for the highest level executives,” Dr. Hudis said. “I didn’t understand why any clinician would have separate rules from any other.”

Mr. Morey said that the hospital is evaluating its process for reviewing conflicts of interest, but that executives like Dr. Baselga had their financial relationships overseen by the board “to protect faculty from being put in a position of having to review their supervisor’s potential conflicts.”

Dr. Baselga is not the only leading researcher to have maintained extensive ties to the drug and health care companies — as some also did under Dr. Varmus. Jedd Wolchok, MD, a noted pioneer in immunotherapy, has financial relationships with more than 30 companies, according to recent disclosures. Charles L. Sawyers, MD, another of the hospital’s biggest names, has founded several cancer startups, one of which Memorial Sloan Kettering has invested in, and serves on the board of the Swiss pharmaceutical giant Novartis.

Ethicists and health experts say having leaders and researchers at nonprofit hospitals sit on corporate boards is especially problematic. When they serve on the board of a publicly traded company, they have a legal duty to the corporation and its shareholders, which can clash with their duty to their patients and primary employers. Those who sit on boards are often paid hundreds of thousands of dollars a year.

“I don’t think you can serve two masters,” said Bernard Lo, MD, who led an influential Institute of Medicine panel in 2009 that investigated financial conflicts in medicine. “The whole reason for being in the cancer care business is that you’re trying to help people in need, and that’s not at all the company’s main purpose. It’s to generate profits on their products.”

A report in November in BioPharma Dive found that 12 of the 19 largest pharmaceutical and biotech companies had at least one board member who also worked at a nonprofit health care institution. A 2014 study in JAMA found that about 40 percent of the largest publicly traded drug companies had a leader of an academic medical center on their boards.

Robert Benezra, PhD, who heads a lab at Memorial Sloan Kettering that focuses on how tumors grow, is the president, chief executive officer and a board member of AngioGenex, a tiny, publicly traded biotech company that is developing drugs to treat cancer based on the discoveries made in his lab.

Though he takes no salary from AngioGenex, Benezra owns nearly 9 percent of the company he helped found through stock or options, setting him up for a lucrative payday if the company is acquired or its drugs come to market.

In 2017, Dr. Benezra wrote to AngioGenex shareholders that a recent policy and leadership change at the hospital “afforded me the freedom to assume a more active role in the company” and to recruit other Memorial Sloan Kettering scientists to work with the company.

Dr. Benezra said in a statement issued through the hospital, “While I do not work directly with patients, I hope that this important science can one day make an impact in the lives of cancer sufferers.”

Mr. Morey said Dr. Benezra spends just 30 hours a year on business related to the publicly traded company. “We’re talking about 45 minutes a week, which is less than what most people spend on Netflix in a night,” Mr. Morey said.

Dr. DeAngelis, the acting physician-in-chief, said the high number of Memorial Sloan Kettering leaders who serve on corporate boards is reflective of their stature. “Maybe we should turn this around and say, we have more people on corporate boards because people value the opinions from our faculty,” she said in an interview.
 

A Staff in Turmoil

Tensions among doctors at the hospital over conflicts of interests mounted through September. On Sept. 28, Colin Begg, PhD, the chairman of its department of epidemiology and biostatistics, wrote to other department heads. “The key substantive issue is that the problems we face were not caused by failures to disclose conflicts. The problems were due to the conflicts themselves,” he wrote in the email, a copy of which was obtained by the Times and ProPublica.

Referring to Dr. Thompson and Douglas A. Warner III, the outgoing chairman of the hospital’s board of managers and overseers, who is known as Sandy, he said: “As far as I can tell neither Sandy nor Craig understand this very basic point. And if you don’t recognize that a problem exists there is no chance you will solve it.”

He also said: “Making billions is not our mission. MSK is a nonprofit with a fundamentally social mission.”

Dr. Begg declined to comment.

Shortly before the doctors met on Oct. 1, Dr. Thompson sounded a conciliatory note. “I want to start by apologizing to the medical staff on behalf of myself and the rest of senior management,” he said, according to a draft transcript of the staff meeting. “The events of the last few weeks have not been handled as well as I would have liked.”

Mr. Warner also addressed the doctors, informing them that the board was assessing whether Dr. Thompson should remain on Merck’s board.

“Should Craig continue to sit on the Merck board? We have no policy on that,” Mr. Warner said, according to the transcript, noting that Dr. Thompson’s role on the board was initially seen as a “good thing” when he joined the hospital. “We need to step back from that now and ask ourselves whether that continues to be appropriate, whether it’s appropriate in the future.”

The next day, Oct. 2, Dr. Thompson announced that he was resigning from both the boards on which he served.

Requests to interview Dr. Thompson and Mr. Warner were declined. Instead, the hospital arranged for reporters to speak to Dr. DeAngelis, who said she saw nothing wrong with the corporate ties that Dr. Thompson had earlier said were under review.

She downplayed the concerns voiced by Dr. Begg about the culture of the hospital. ”He is a biostatistician. He does not work with patients. He works with data,” she said, adding that he does not have “as full an understanding” about policies to prevent doctors with corporate ties from having an undue influence on clinical trials.

Dr. Thompson and two deputies, including Dr. DeAngelis, sent a note to hospital doctors on Dec. 20, warning them about this article. While it mentioned the ongoing review, it offered a full-throated defense of those serving on corporate boards.

“We expect the piece to question the ethics of some of our most accomplished researchers and clinicians. We want you to know that we reject these insinuations and we stand behind our faculty 100 percent.”
 

Katie Thomas covers the pharmaceutical industry for The New York Times.

This story republished by permission of ProPublica.

Hundreds of doctors packed an auditorium at Memorial Sloan Kettering Cancer Center on Oct. 1, deeply angered by revelations that the hospital’s top medical officer and other leaders had cultivated lucrative relationships with for-profit companies.

One by one, they stood up to challenge the stewardship of their beloved institution, often to emotional applause. Some speakers accused their leaders of letting the quest to make more money undermine the hospital’s mission. Others bemoaned a rigid, hierarchical management that had left them feeling they had no real voice in the hospital’s direction.

“Slowly, I’ve seen more and more of the higher-up meetings happening with people who are dressed up in suits as opposed to white coats,” said Viviane Tabar, MD, chairwoman of the neurosurgery department.

“The corporatization of this institution is clear to many of us who have been here a long time,” said Carol L. Brown, MD, a gynecologic cancer surgeon, according to an audio recording of the meeting.

The meeting ended after several doctors advocated an immediate no-confidence vote in the hospital’s senior leadership. The turmoil followed reports by The New York Times and ProPublica that the hospital’s chief medical officer, José Baselga, MD, had been paid millions by drug and health care companies and failed to disclose those ties more than 100 times in medical journals, and that hospital insiders had made lucrative side deals that stood to earn them handsome profits, sometimes for work they had done on the job.

The day after the meeting, the hospital’s chief executive, Craig B. Thompson, MD, promised greater openness with rank-and-file doctors about decisionmaking. He also committed to doing the “root-cause analysis” requested by the doctors of how “egregious conflicts of interest,” as one physician put it, had been allowed to happen.

Other hospitals around the country are confronting similar dilemmas. But at Memorial Sloan Kettering, one of the nation’s leading cancer research and treatment centers, they are especially acute. Internal emails, audio recordings of meetings and interviews with doctors show how this major New York institution has struggled to contain a crisis of confidence in its leadership.

Closer ties between nonprofit research centers like Memorial Sloan Kettering and corporations are being fueled by a rush of potentially breakthrough cancer treatments. Venture capital firms and drug companies have looked to cash in on the scientific discoveries, said Brad Loncar, the founder of an investment fund that focuses on cancer. “Money follows success,” he said, and Memorial Sloan Kettering has been a focus “because they conduct terrific science there.”

In recent years, the hospital, like its competitors, has struck increasingly sophisticated deals to commercialize its discoveries, in some cases receiving equity stakes in startups rather than simply collecting royalties.

The predicament of Memorial Sloan Kettering also reflects a shift in its own culture. Its prior chief executive, Harold E. Varmus, MD, a Nobel Prize-winning scientist, personally kept companies at arm’s length, while Dr. Thompson, also a respected cancer researcher, has more fully embraced such relationships. The new approach has been applauded by some for expanding access to the cancer center’s discoveries, even as others have worried that the hospital may be losing sight of its mission.

Its leaders and top researchers also hold influential positions in the corporate world. When news of Dr. Baselga’s disclosure lapses broke in September, 12 doctors and researchers at the hospital served on the boards of publicly traded companies, more than at any other major cancer center, according to a review by the Times and ProPublica. Dr. Baselga has since resigned from the hospital and the two boards he served on. And a day after the physicians’ meeting on Oct. 1, Dr. Thompson resigned from the boards of the pharmaceutical giant Merck and Charles River Laboratories, a health care company, that together had paid him $585,050 in compensation in 2017.

The concern of ethicists and health experts is that a bias in favor of industry can unduly influence scientific research and medical treatments and remove a valuable check on soaring drug prices.

“We do have to sort of decide which side of this we’re on, or at least notice that we are feeding at the very trough that is causing worse access here than in any other Western country,” Peter B. Bach, MD, director of the hospital’s Center for Health Policy and Outcomes, said at the Oct. 1 meeting.

The problems at Memorial Sloan Kettering have shaken other cancer centers. At Dana-Farber Cancer Institute, officials have said they are considering whether Laurie H. Glimcher, MD, their chief executive, and others should continue to serve on the boards of publicly traded companies, including the drugmaker GlaxoSmithKline, on whose board Dr. Glimcher sits.

At the Fred Hutchinson Cancer Research Center in Seattle, a task force is reviewing the conflict-of-interest policies that govern employees’ financial relationships with drug companies. And medical centers around the country have instructed researchers to review their financial disclosures to medical journals, leading to a series of corrections to scientific articles.

Even as Memorial Sloan Kettering leaders have promised greater transparency, they have engaged a public affairs firm, SKDKnickerbocker, to manage their message and have aggressively pushed back against the idea that the hospital’s leaders are too close to industry.

“I can see how someone might think that business relationships are problematic,” said Lisa DeAngelis, MD, who has stepped into Dr. Baselga’s former position at Memorial Sloan Kettering on an acting basis. “But I’m telling you, as someone who works with patients, and I’ve worked with patients throughout my entire career here, that working with industry has helped me save lives.”

The Times and ProPublica asked to speak to Dr. Tabar and Dr. Brown about the critical remarks they made about the hospital’s direction at the Oct. 1 meeting. Mike Morey, managing director of the communications firm engaged by the hospital, arranged for them to speak to reporters on the phone while he listened. The doctors said they were not specifically referring to Memorial Sloan Kettering during the meeting that was recorded by one of those in attendance, but to broader changes in the medical world.

Defining an Institution’s Role

Founded in 1884 as the New York Cancer Hospital, Memorial Sloan Kettering was the first hospital in the country devoted exclusively to treating cancer. Its benefactors have included some of the wealthiest families in America, from the Astors and Rockefellers in its early years to the Kochs today.

It now operates more than 120 research laboratories, employs more than 1,000 doctors, admits some 23,500 patients a year, operates one of the world’s largest clinical trial programs and had revenues of nearly $4.5 billion in 2017. It recently completed a $3.5 billion fundraising drive, and its charity ball remains a fixture on New York’s social calendar.

As a leading force in cancer research, the hospital has long grappled with striking a balance in its collaborations with drug companies. While it did business with industry during the tenure of Dr. Varmus, a former director of the National Institutes of Health, he and a top deputy, Robert E. Wittes, MD, did not consult for companies, own their stock or serve on their boards, according to several people who worked for Dr. Varmus while he was at the hospital from 2000 to 2010. Dr. Varmus and Dr. Wittes declined to comment.

But some on the hospital’s board wanted its chief executive to do more to encourage company-financed clinical trials and to bring discoveries to market. In an interview, John R. Gunn, the cancer center’s chief operating officer from 1987 to 2015, said board members felt gems of research were “lying fallow and nobody was kind of pushing it, to commercialize it.”

By the time Dr. Varmus left to direct the National Cancer Institute in 2010, Memorial Sloan Kettering’s board was looking for a leader who was as comfortable in a corporate boardroom as in the lab, according to several longtime current and former cancer center employees.

Dr. Thompson met that criteria. He headed the Abramson Cancer Center at the University of Pennsylvania, was the co-founder of a biotech startup, Agios, and served on the board of Merck.

His early tenure was marred by controversy. In 2011 and 2012, he was sued by his former employers, the Abramson center and the University of Pennsylvania, which accused him of walking off with valuable research and using it to start Agios. At the time, Dr. Thompson denied wrongdoing and the suits were later settled for an undisclosed sum.

In 2012, Dr. Thompson hired Dr. Baselga to be the top physician at Memorial Sloan Kettering. Dr. Baselga, who had made his name as a key investigator of the breast cancer drug Herceptin, was also seen as having bridged the worlds of research and industry. Dr. DeAngelis, the hospital’s acting physician-in-chief, said that under Dr. Baselga, clinical trials were approved more quickly, helping speed treatments to patients.

But several doctors who worked under Dr. Baselga said in interviews that he had an abrasive style and created a culture where ties to industry were not kept in check. Dr. Baselga has not responded to requests for comment.

In his years at Memorial Sloan Kettering, Dr. Baselga’s personal financial conflicts were handled differently from those of other doctors, according to Clifford A. Hudis, MD, who was chairman of the hospital’s conflict-of-interest advisory committee through early 2016, when he left to become chief executive of the American Society of Clinical Oncology.

Dr. Baselga’s conflicts were not overseen by Dr. Hudis’ committee, but by the audit committee of the hospital’s board of directors. “I was told this was pretty standard for the highest level executives,” Dr. Hudis said. “I didn’t understand why any clinician would have separate rules from any other.”

Mr. Morey said that the hospital is evaluating its process for reviewing conflicts of interest, but that executives like Dr. Baselga had their financial relationships overseen by the board “to protect faculty from being put in a position of having to review their supervisor’s potential conflicts.”

Dr. Baselga is not the only leading researcher to have maintained extensive ties to the drug and health care companies — as some also did under Dr. Varmus. Jedd Wolchok, MD, a noted pioneer in immunotherapy, has financial relationships with more than 30 companies, according to recent disclosures. Charles L. Sawyers, MD, another of the hospital’s biggest names, has founded several cancer startups, one of which Memorial Sloan Kettering has invested in, and serves on the board of the Swiss pharmaceutical giant Novartis.

Ethicists and health experts say having leaders and researchers at nonprofit hospitals sit on corporate boards is especially problematic. When they serve on the board of a publicly traded company, they have a legal duty to the corporation and its shareholders, which can clash with their duty to their patients and primary employers. Those who sit on boards are often paid hundreds of thousands of dollars a year.

“I don’t think you can serve two masters,” said Bernard Lo, MD, who led an influential Institute of Medicine panel in 2009 that investigated financial conflicts in medicine. “The whole reason for being in the cancer care business is that you’re trying to help people in need, and that’s not at all the company’s main purpose. It’s to generate profits on their products.”

A report in November in BioPharma Dive found that 12 of the 19 largest pharmaceutical and biotech companies had at least one board member who also worked at a nonprofit health care institution. A 2014 study in JAMA found that about 40 percent of the largest publicly traded drug companies had a leader of an academic medical center on their boards.

Robert Benezra, PhD, who heads a lab at Memorial Sloan Kettering that focuses on how tumors grow, is the president, chief executive officer and a board member of AngioGenex, a tiny, publicly traded biotech company that is developing drugs to treat cancer based on the discoveries made in his lab.

Though he takes no salary from AngioGenex, Benezra owns nearly 9 percent of the company he helped found through stock or options, setting him up for a lucrative payday if the company is acquired or its drugs come to market.

In 2017, Dr. Benezra wrote to AngioGenex shareholders that a recent policy and leadership change at the hospital “afforded me the freedom to assume a more active role in the company” and to recruit other Memorial Sloan Kettering scientists to work with the company.

Dr. Benezra said in a statement issued through the hospital, “While I do not work directly with patients, I hope that this important science can one day make an impact in the lives of cancer sufferers.”

Mr. Morey said Dr. Benezra spends just 30 hours a year on business related to the publicly traded company. “We’re talking about 45 minutes a week, which is less than what most people spend on Netflix in a night,” Mr. Morey said.

Dr. DeAngelis, the acting physician-in-chief, said the high number of Memorial Sloan Kettering leaders who serve on corporate boards is reflective of their stature. “Maybe we should turn this around and say, we have more people on corporate boards because people value the opinions from our faculty,” she said in an interview.
 

A Staff in Turmoil

Tensions among doctors at the hospital over conflicts of interests mounted through September. On Sept. 28, Colin Begg, PhD, the chairman of its department of epidemiology and biostatistics, wrote to other department heads. “The key substantive issue is that the problems we face were not caused by failures to disclose conflicts. The problems were due to the conflicts themselves,” he wrote in the email, a copy of which was obtained by the Times and ProPublica.

Referring to Dr. Thompson and Douglas A. Warner III, the outgoing chairman of the hospital’s board of managers and overseers, who is known as Sandy, he said: “As far as I can tell neither Sandy nor Craig understand this very basic point. And if you don’t recognize that a problem exists there is no chance you will solve it.”

He also said: “Making billions is not our mission. MSK is a nonprofit with a fundamentally social mission.”

Dr. Begg declined to comment.

Shortly before the doctors met on Oct. 1, Dr. Thompson sounded a conciliatory note. “I want to start by apologizing to the medical staff on behalf of myself and the rest of senior management,” he said, according to a draft transcript of the staff meeting. “The events of the last few weeks have not been handled as well as I would have liked.”

Mr. Warner also addressed the doctors, informing them that the board was assessing whether Dr. Thompson should remain on Merck’s board.

“Should Craig continue to sit on the Merck board? We have no policy on that,” Mr. Warner said, according to the transcript, noting that Dr. Thompson’s role on the board was initially seen as a “good thing” when he joined the hospital. “We need to step back from that now and ask ourselves whether that continues to be appropriate, whether it’s appropriate in the future.”

The next day, Oct. 2, Dr. Thompson announced that he was resigning from both the boards on which he served.

Requests to interview Dr. Thompson and Mr. Warner were declined. Instead, the hospital arranged for reporters to speak to Dr. DeAngelis, who said she saw nothing wrong with the corporate ties that Dr. Thompson had earlier said were under review.

She downplayed the concerns voiced by Dr. Begg about the culture of the hospital. ”He is a biostatistician. He does not work with patients. He works with data,” she said, adding that he does not have “as full an understanding” about policies to prevent doctors with corporate ties from having an undue influence on clinical trials.

Dr. Thompson and two deputies, including Dr. DeAngelis, sent a note to hospital doctors on Dec. 20, warning them about this article. While it mentioned the ongoing review, it offered a full-throated defense of those serving on corporate boards.

“We expect the piece to question the ethics of some of our most accomplished researchers and clinicians. We want you to know that we reject these insinuations and we stand behind our faculty 100 percent.”
 

Katie Thomas covers the pharmaceutical industry for The New York Times.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

Single-agent therapy with quizartinib slightly but significantly prolonged survival – compared with salvage chemotherapy – for patients with relapsed/refractory acute myeloid leukemia (AML) bearing the FLT3-ITD mutation, results of the phase 3 randomized QuANTUM-R trial showed.

Neil Osterweil/MDedge News

Median overall survival (OS), the trial’s primary endpoint, was 6.2 months for 245 patients randomized to quizartinib, compared with 4.7 months for 122 patients assigned to salvage chemotherapy, a difference that translated into a hazard ratio (HR) for death of 0.76 (P = .0177), reported Jorge E. Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This study is the first study that demonstrates in a randomized fashion an overall survival benefit in the salvage setting for patients with FLT-3 mutated refractory or relapsed AML,” he said at the annual meeting of the American Society of Hematology. “I will also add that these results you saw here are very consistent with all the trials previously with quizartinib with more than 1,000 patients treated.”

Quizartinib, a tyrosine kinase inhibitor (TKI), has previously been shown to be associated with higher response rates among patients with AML bearing the FLT3-ITD mutation than in patients with AML without the deleterious mutation.

Investigators in the QuANTUM-R trial enrolled 367 adults with FTL3-ITD mutated AML that was refractory to the most recent line of therapy or had relapsed within 6 months of first remission, with or without hematopoietic stem cell transplant (HSCT).

The patients had all received at least one cycle of standard-dose induction therapy containing an anthracycline or mitoxantrone, and had a 3% or greater FLT3-ITD allelic ratio in their AML cells.

The patients were randomly assigned on a 2:1 basis to receive either quizartinib or salvage chemotherapy. Quizartinib was dosed 30 mg per day for 15 days, which could be titrated upward to 60 mg daily if the corrected QT interval by Fredericia (QTcF) was 450 ms or less on day 16.

Chemotherapy was the investigator’s choice of one of three specified regimens: either low-dose cytarabine (LoDAC); mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC); or fludarabine, cytarabine, and granulocyte-colony stimulating factor (G-CSF) with idarubicin (FLAG-IDA). Up to two cycles of MEC or FLAG-IDA were permitted; quizartinib and LoDAC were given until lack of benefit, unacceptable toxicity, or until the patient went on to HSCT.

The analysis was by intention-to-treat. In the quizartinib arm, 241 of the 245 randomized patients (98.4%) received treatment. In the chemotherapy arm, 94 of 122 randomized patients (77%) received chemotherapy. Of this group, 22 received LoDAC, 25 received MEC, and 47 received FLAG-IDA.

The median treatment duration was 97 days in the quizartinib arm versus 28 days (one cycle) in the chemotherapy arm.

The 1-year overall survival rate was 27% for patients assigned to quizartinib, compared with 20% for patients assigned to chemotherapy.

An analysis of OS by subgroup indicated a trend or significant benefit for quizartinib in all categories, including age over or under 65 years, sex, low or high-intensity chemotherapy, response to prior therapy, FLT3 variant allele frequency, prior allogenic HSCT, and AML risk score.

For the secondary endpoint of event-free survival in the ITT population, there was no significant difference between the study arms. In a per-protocol analysis, however, median event-free survival was better with quizartinib, at 1.4 months versus 0.0 months (P = .006).

In all, 32% of patients assigned to quizartinib went on to HSCT, compared with 12% of patients randomized to chemotherapy.

Rates of treatment-emergent adverse events (TEAEs) were similar between the study arms, despite higher total drug exposure in patients randomized to quizartinib. The most frequent grade 3 or greater TEAEs in each arm were infections and cytopenia-related events.

Two patients discontinued quizartinib due to QTcF prolongation. Grade 3 QTcF (greater than 500 ms) occurred in 3% of patients treated with quizartinib, but no grade 4 cases were seen.

The adverse event profile for patients who resumed quizartinib following HSCT was similar to that of patients who received the drug pretransplant.

The combination of standard chemotherapy, with or without quizartinib, is currently being explored in the phase 3 QuANTUM-First trial, Dr. Cortes said.

Daiichi Sankyo sponsored the trial. Dr. Cortes reported financial relationships with Daiichi Sankyo, Pfizer, Arog, Astellas Pharma, and Novartis.

SOURCE: Cortes JE et al. ASH 2018, Abstract 563.

Do food delivery programs reduce the use of costly health services and decrease medical spending in a population of patients dually eligible for Medicare and Medicaid?

Researchers in Massachusetts wanted to determine whether home meal delivery of either medically tailored food or nontailored food reduces the use of selected health care services and medical spending in a sample of adult “dual eligibles.”

“Compared with matched nonparticipants, participants had fewer emergency department visits in both the medically tailored meal program and the nontailored food program,” the investigators found. “Participants in the medically tailored meal program also had fewer inpatient admissions and lower medical spending. Participation in the nontailored food program was not associated with fewer inpatient admissions but was associated with lower medical spending.”
 

Reference

Berkowitz SA et al. Meal delivery programs reduce the use of costly health care in dually eligible Medicare and Medicaid beneficiaries. Health Aff (Millwood). 2018 Apr;37(4):535-42.

Do food delivery programs reduce the use of costly health services and decrease medical spending in a population of patients dually eligible for Medicare and Medicaid?

Researchers in Massachusetts wanted to determine whether home meal delivery of either medically tailored food or nontailored food reduces the use of selected health care services and medical spending in a sample of adult “dual eligibles.”

“Compared with matched nonparticipants, participants had fewer emergency department visits in both the medically tailored meal program and the nontailored food program,” the investigators found. “Participants in the medically tailored meal program also had fewer inpatient admissions and lower medical spending. Participation in the nontailored food program was not associated with fewer inpatient admissions but was associated with lower medical spending.”
 

Reference

Berkowitz SA et al. Meal delivery programs reduce the use of costly health care in dually eligible Medicare and Medicaid beneficiaries. Health Aff (Millwood). 2018 Apr;37(4):535-42.

Do food delivery programs reduce the use of costly health services and decrease medical spending in a population of patients dually eligible for Medicare and Medicaid?

Researchers in Massachusetts wanted to determine whether home meal delivery of either medically tailored food or nontailored food reduces the use of selected health care services and medical spending in a sample of adult “dual eligibles.”

“Compared with matched nonparticipants, participants had fewer emergency department visits in both the medically tailored meal program and the nontailored food program,” the investigators found. “Participants in the medically tailored meal program also had fewer inpatient admissions and lower medical spending. Participation in the nontailored food program was not associated with fewer inpatient admissions but was associated with lower medical spending.”
 

Reference

Berkowitz SA et al. Meal delivery programs reduce the use of costly health care in dually eligible Medicare and Medicaid beneficiaries. Health Aff (Millwood). 2018 Apr;37(4):535-42.

Resources

US Department of Health and Human Services. Physical Activity Guidelines for Americans. 2nd ed. Office of Disease Prevention and Health Promotion Web site. Published 2018. https://health.gov/paguidelines/second-edition/. Accessed January 7, 2019.

Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA. 2018;320:2020-2028.

Resources

US Department of Health and Human Services. Physical Activity Guidelines for Americans. 2nd ed. Office of Disease Prevention and Health Promotion Web site. Published 2018. https://health.gov/paguidelines/second-edition/. Accessed January 7, 2019.

Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA. 2018;320:2020-2028.

Resources

US Department of Health and Human Services. Physical Activity Guidelines for Americans. 2nd ed. Office of Disease Prevention and Health Promotion Web site. Published 2018. https://health.gov/paguidelines/second-edition/. Accessed January 7, 2019.

Piercy KL, Troiano RP, Ballard RM, et al. The Physical Activity Guidelines for Americans. JAMA. 2018;320:2020-2028.

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief

This month’s issue is packed with important science – nice to get back to medicine and not focus on politics. On page one, we highlight important new clinical guidance on the use of thiopurines in inflammatory bowel disease. This clinical practice update has some very specific and clear recommendations about thiopurines, especially in combination with biologic agents. As any clinician knowns, treatment of IBD has become complex from both a biologic standpoint and because we now recognize the importance of social determinants of health in our management of chronic diseases. We have seen an enormous outpouring of work that helps gastroenterologists develop multidisciplinary “homes” for IBD patients. These programs are now becoming best practice standards. Such approaches are practical for both academic and community GI practices. Best practice for our IBD patients now involves following clinical guidelines, understanding the impact of IBD on patients’ social and behavioral health and the incorporation of support services (or referral), and outcomes measurement. This clinical practice update will help us enhance our medical therapy for patients with both Crohn’s disease and ulcerative colitis.

Other stories include a review of the new AGA clinical practice update on endoscopic submucosal dissection for early stage cancers with important information about technique, indications, and management of complications. Questions about our approach to prevention of GI bleeding for patients in the ICU are raised by a new multicentered trial of PPI use in over 3,500 patients. Essentially, PPI prophylaxis should be reserved for seriously ill patients at high risk for bleeding – prophylaxis may not be needed in other ICU patients. Finally, another study does not support use of probiotics (at least in the current formulation) in children with gastroenteritis.

I hope you enjoy the issue and that you had a wonderful year’s end. We look forward to more excitement in 2019.

John I. Allen, MD, MBA, AGAF
Editor in Chief

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

Elevated eosinophil levels and interleukin-4 (IL-4) levels were significantly associated with an increased risk of overlapping asthma and chronic obstructive pulmonary disease (COPD) in firefighters exposed to toxins at the World Trade Center on Sept. 11, 2001.

Courtesy Andrea Booher/FEMA News Photo

Patients with asthma/COPD overlap experience decreased quality of life and increased mortality, compared with patients who have either isolated COPD or isolated asthma, and longitudinal data on risk factors for the overlapping condition are lacking, wrote Ankura Singh, MPH, of Albert Einstein College of Medicine, New York, and colleagues.

In a study published in CHEST, the researchers reviewed data from 2,137 firefighters exposed to toxins at the World Trade Center on 9/11. The study participants underwent a bronchodilator pulmonary function test between Sept. 9, 2001, and Sept. 10, 2017, and at least three routine monitoring pulmonary function tests between these two dates.

In a multivariate analysis, eosinophil concentration of at least 300 cells/mcL was a significant predictor of asthma/COPD overlap. Serum IL-4 levels also were significant predictors of asthma/COPD overlap (hazard ratio, 1.51).

In addition, a greater concentration of IL-21 was associated with both isolated asthma and isolated COPD, but not with the overlap.

The study results were strengthened by the availability of pre-exposure medical data for the firefighters and the close follow-up, although limitations included the mostly white male population and a limited definition of asthma, the researchers noted.

However, the findings suggest that “high eosinophil concentrations, uniquely associated with asthma/COPD overlap in this population, may reflect biological pathways that predispose one to exaggerated inflammation and/or poor counterregulatory responses to inflammation, leading to reversible and fixed airflow obstruction,” they wrote. Consequently, early interventions targeting specific inflammatory pathways may improve lung function outcomes.

The study was supported in part by the National Institute of Occupational Safety and Health and the National Institutes of Health.

SOURCE: Singh A et al. CHEST. 2018 Dec;154;1301-10.

The currently recommended method for hospital antimicrobial stewardship programs (ASPs) to measure antibiotic use is Days of Therapy/1,000 patient-days, but there are a few disadvantages of using the DOT, said Maryrose Laguio-Vila, MD, coauthor of a recent study on stewardship.

luchschen/Thinkstock

“For accurate measurement, it requires information technology (IT) support to assist an ASP in generating reports of antibiotic prescriptions and administrations to patients, often from an electronic medical record (EMR). In hospitals where there is no EMR, DOT is probably not easily done and would have to be manually extracted (a herculean task),” she said. “Second, DOT tends to be an aggregate measurement of antibiotics used at an institution or hospital location; if an ASP does a specific intervention targeting a group of antibiotics or infectious indication, changes in the hospital-wide DOT or drug-class DOT may not accurately reflect the exact impact of an ASP’s intervention.”

The paper offers an alternative/supplemental method for ASPs to quantify their impact on antibiotic use without using an EMR or needing IT support: Days of Therapy Avoided. “DOTA can be tracked prospectively (or retrospectively) with each intervention an ASP makes, and calculates an exact amount of antibiotic use avoided,” Dr. Laguio-Vila said. “If the ASP also tracks the types of antibiotic recommendations made according to infectious indication, comparison of DOTA between indications – such as pneumonia versus UTI [urinary tract infection] – can lead to ideas of which type of indication needs clinical guidelines development, or order set revision, or which type of infection the ASP should target to reduce high-risk antibiotics.”

Also, she added, because most ASPs have several types of interventions at once (such as education on pneumonia guidelines, as well as penicillin-allergy assessment), aggregate assessments of institutional antibiotic use like the DOT cannot quantify how much impact a specific intervention has accomplished. DOTA may offer a fairer assessment of the direct changes in antibiotic use resulting from specific ASP activities, because tracking DOTA is extracted from each specific patient intervention.

“Now that the Joint Commission has a requirement that all hospitals seeking JC accreditation have some form of an ASP in place and measure antibiotic use in some way at their institution, there may be numerous hospitals facing the same challenges with calculating a DOT. DOTA would meet these requirements, but in a ‘low tech’ way,” Dr. Laguio-Vila said. “For hospitalists with interests in being the antibiotic steward or champion for their institution, DOTA is an option for measuring antibiotic use.”
 

Reference

Datta S et al. Days of therapy avoided: A novel method for measuring the impact of an antimicrobial stewardship program to stop antibiotics. J Hosp Med. 2018 Feb 8. doi: 10.12788/jhm.2927.






 

The currently recommended method for hospital antimicrobial stewardship programs (ASPs) to measure antibiotic use is Days of Therapy/1,000 patient-days, but there are a few disadvantages of using the DOT, said Maryrose Laguio-Vila, MD, coauthor of a recent study on stewardship.

luchschen/Thinkstock

“For accurate measurement, it requires information technology (IT) support to assist an ASP in generating reports of antibiotic prescriptions and administrations to patients, often from an electronic medical record (EMR). In hospitals where there is no EMR, DOT is probably not easily done and would have to be manually extracted (a herculean task),” she said. “Second, DOT tends to be an aggregate measurement of antibiotics used at an institution or hospital location; if an ASP does a specific intervention targeting a group of antibiotics or infectious indication, changes in the hospital-wide DOT or drug-class DOT may not accurately reflect the exact impact of an ASP’s intervention.”

The paper offers an alternative/supplemental method for ASPs to quantify their impact on antibiotic use without using an EMR or needing IT support: Days of Therapy Avoided. “DOTA can be tracked prospectively (or retrospectively) with each intervention an ASP makes, and calculates an exact amount of antibiotic use avoided,” Dr. Laguio-Vila said. “If the ASP also tracks the types of antibiotic recommendations made according to infectious indication, comparison of DOTA between indications – such as pneumonia versus UTI [urinary tract infection] – can lead to ideas of which type of indication needs clinical guidelines development, or order set revision, or which type of infection the ASP should target to reduce high-risk antibiotics.”

Also, she added, because most ASPs have several types of interventions at once (such as education on pneumonia guidelines, as well as penicillin-allergy assessment), aggregate assessments of institutional antibiotic use like the DOT cannot quantify how much impact a specific intervention has accomplished. DOTA may offer a fairer assessment of the direct changes in antibiotic use resulting from specific ASP activities, because tracking DOTA is extracted from each specific patient intervention.

“Now that the Joint Commission has a requirement that all hospitals seeking JC accreditation have some form of an ASP in place and measure antibiotic use in some way at their institution, there may be numerous hospitals facing the same challenges with calculating a DOT. DOTA would meet these requirements, but in a ‘low tech’ way,” Dr. Laguio-Vila said. “For hospitalists with interests in being the antibiotic steward or champion for their institution, DOTA is an option for measuring antibiotic use.”
 

Reference

Datta S et al. Days of therapy avoided: A novel method for measuring the impact of an antimicrobial stewardship program to stop antibiotics. J Hosp Med. 2018 Feb 8. doi: 10.12788/jhm.2927.






 

The currently recommended method for hospital antimicrobial stewardship programs (ASPs) to measure antibiotic use is Days of Therapy/1,000 patient-days, but there are a few disadvantages of using the DOT, said Maryrose Laguio-Vila, MD, coauthor of a recent study on stewardship.

luchschen/Thinkstock

“For accurate measurement, it requires information technology (IT) support to assist an ASP in generating reports of antibiotic prescriptions and administrations to patients, often from an electronic medical record (EMR). In hospitals where there is no EMR, DOT is probably not easily done and would have to be manually extracted (a herculean task),” she said. “Second, DOT tends to be an aggregate measurement of antibiotics used at an institution or hospital location; if an ASP does a specific intervention targeting a group of antibiotics or infectious indication, changes in the hospital-wide DOT or drug-class DOT may not accurately reflect the exact impact of an ASP’s intervention.”

The paper offers an alternative/supplemental method for ASPs to quantify their impact on antibiotic use without using an EMR or needing IT support: Days of Therapy Avoided. “DOTA can be tracked prospectively (or retrospectively) with each intervention an ASP makes, and calculates an exact amount of antibiotic use avoided,” Dr. Laguio-Vila said. “If the ASP also tracks the types of antibiotic recommendations made according to infectious indication, comparison of DOTA between indications – such as pneumonia versus UTI [urinary tract infection] – can lead to ideas of which type of indication needs clinical guidelines development, or order set revision, or which type of infection the ASP should target to reduce high-risk antibiotics.”

Also, she added, because most ASPs have several types of interventions at once (such as education on pneumonia guidelines, as well as penicillin-allergy assessment), aggregate assessments of institutional antibiotic use like the DOT cannot quantify how much impact a specific intervention has accomplished. DOTA may offer a fairer assessment of the direct changes in antibiotic use resulting from specific ASP activities, because tracking DOTA is extracted from each specific patient intervention.

“Now that the Joint Commission has a requirement that all hospitals seeking JC accreditation have some form of an ASP in place and measure antibiotic use in some way at their institution, there may be numerous hospitals facing the same challenges with calculating a DOT. DOTA would meet these requirements, but in a ‘low tech’ way,” Dr. Laguio-Vila said. “For hospitalists with interests in being the antibiotic steward or champion for their institution, DOTA is an option for measuring antibiotic use.”
 

Reference

Datta S et al. Days of therapy avoided: A novel method for measuring the impact of an antimicrobial stewardship program to stop antibiotics. J Hosp Med. 2018 Feb 8. doi: 10.12788/jhm.2927.






 

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Women with systemic lupus erythematosus (SLE) were not more likely to take aspirin during pregnancy than when not pregnant, despite the potential to reduce preeclampsia risk, based on data from 300 women.

Although aspirin is recommended to reduce preeclampsia risk in pregnant SLE patients, data on current practice patterns are limited, wrote Arielle Mendel, MD, of McGill University, Montreal, and colleagues in Annals of the Rheumatic Diseases.

The researchers identified 475 pregnancies among 300 women aged 18-45 years who were pregnant during the study period from 2000 to 2017. The average duration of SLE duration at the time of pregnancy was 5.6 years, and approximately half (51%) of pregnancies had one or more traditional preeclampsia risk factors. In addition, 33% of the women had positive antiphospholipid antibodies (aPL).

Overall, 25% of the pregnancies included aspirin use, with no significant difference among those with one or more risk factors, any individual risk factor, or nephritis.

The study population was 44% white, 19% black, 14% Asian, 13% Hispanic, 5% from the Indian subcontinent, 1% Native American, and 5% other ethnicities.

Approximately 34% of white patients and 32% of Hispanic patients were exposed to aspirin, compared with 18% and 20% of black and Asian patients, respectively. Aspirin use did not increase over the study period, although there was a trend for increased use in patients with a positive aPL, compared with those with no aPL.

“The low aspirin use among black SLE subjects is noteworthy given the worse reproductive outcomes observed in this population,” the researchers wrote.

The findings were limited by several factors, including a lack of data on gestational age and pregnancy outcomes, the researchers noted. However, the results highlight the gap between recommendations and practice, and the need for additional research on aspirin use in pregnant SLE patients.

The study was supported in part by a McGill University Health Centre Research Award; the researchers reported no financial conflicts.

SOURCE: Mendel A et al. Ann Rheum Dis. 2018 Dec 20. doi: 10.1136/annrheumdis-2018-214434.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Patients with RA who initiated abatacept had significantly lower risk of hospitalized infection, compared with those who initiated a tumor necrosis factor inhibitor (TNFi), based on data from more than 11,000 matched pairs of patients.

“Given similar efficacy between abatacept and TNFi as biologic therapies for treatment of RA, one of the main determinants in choosing between the medications is minimizing the risk of infection,” wrote Sarah K. Chen, MD, of Brigham and Women’s Hospital in Boston, and her colleagues.

In a study published in Arthritis Care & Research, the researchers identified 11,248 propensity score–matched pairs of RA patients aged 18 years and older with at least two RA diagnoses who initiated abatacept or a TNFi. The average age of the patients was 56 years; 83% were women. The primary outcome was hospitalized infection. Patients with conditions that might increase the risk of infection, such as malignancy, HIV/AIDS, renal dialysis, or a history of bone marrow transplant were excluded, as were patients who had used rituximab, tocilizumab, or tofacitinib before the start of the study.

Overall, the incidence rate for a hospitalized infection was 37 per 1,000 person-years among abatacept patients and 47 per 1,000 person-years among TNFi patients (hazard ratio, 0.78). In a subgroup analysis, the difference in infection rate remained significant between abatacept and infliximab (HR, 0.63), and no significant difference occurred between abatacept and etanercept.

The researchers also examined secondary outcomes including bacterial infection, herpes zoster, and infections of various organs. The risk of these was similar between abatacept and TNF inhibitors for all but pulmonary infections, which was lower for abatacept.

The study was supported by an investigator-sponsored research grant from Bristol-Myers Squibb. Dr. Chen had no financial conflicts to disclose.

SOURCE: Chen SK et al. Arthritis Care Res. 2018 Dec 20. doi: 10.1002/acr.23824.

Having taken the SVS “burnout” survey, I felt that it really never got into the “whys” of what was making individuals burn out. It dealt more with the consequences of the whys rather than the whys themselves, and it is these whys that must be addressed to assist in the prevention of burnout. I would like to comment on my experience of some, certainly not all, of the possible whys related to both inherent stressors and “administrator induced stressors” encountered in my 42-year vascular surgery practice that can easily cause burnout.

I believe there are several major areas that need to be evaluated to understand the causes of burnout because the complexities of today’s practice environment demand a different approach to the practice of vascular surgery for the well-being of the vascular surgeon. These complexities include the emotional baggage inherent in a practice, practice structure, unpredictable time management issues of running a practice, and hospital administration’s decisions creating unintended consequences for the vascular surgeon.

By its very nature, vascular surgery is a difficult field with many inherent stressors, endovascular innovations not withstanding. The initial emotional stressors may well be those of dealing with elderly patients with multiple severe comorbidities, poor outcomes, and the ensuing consequences. With the aging of the population, these stressors will only increase, yet compensation to treat these feeble patients has yet to rise to a level commensurate with the risk factors and complications the surgeon must deal with. Over time this will take its toll on some.

Which practice pattern one chooses to utilize – solo, group, or employed – also plays an important part. The presence or absence of appropriate help and backup for difficult cases, call coverage, and partnership financial packages can be either very stress producing or stress relieving. Are practice responsibilities and finances equally split so as to achieve a reasonable lifestyle, or is there a hierarchy of work and financial gain by which some must shoulder more of the burden for less pay than others? This is the beginning of the income versus lifestyle conflict and becomes a seriously stressful trap when one is short sighted and does not go for the long term. In our practice, we rotate the work and split the gain equally in return for the most valuable commodity of all: free time.

Time management is of paramount importance in completing a schedule, yet the paradox of the vascular world is its inherent unpredictability. There are difficult, time-consuming cases; unexpected, recurrent vascular problems in the same patient; urgent consults needing treatment within a few days; and the inevitable emergency room call for immediate treatment, day or night, for an embolism, vascular trauma, or ruptured aneurysm – not to mention the hospital committees or other responsibilities in the everyday life of a vascular surgeon.

One’s schedule requires dedicated time and attention yet the urgent/emergent issues interrupting one’s daily schedule ensures that the only predictability is unpredictability. This is a source of burnout. My experience over the years has been that about 25% of our practice load comes on an urgent to emergent basis, often causing considerable scheduling problems both in the operating room and at the office – again, issues that can cause tremendous stress for many. Without a large group, these constant stressors become difficult to shoulder.

Then there are the hospital-induced stressors caused by poorly conceived administrative decrees. One example is when emergency rooms need vascular services but no contracts are offered to secure these services, in which physicians are merely expected to provide 24/7 services. Once a physician has been called in for a case in the middle of the night, the stress of carrying on the next day becomes greater for that physician unless a system is in place for designated calls, which some larger groups have worked out.

Another example is the tendency to grant interventional privileges to those incapable of treating their operative complications without any consideration for who would reimburse those who come in after and how. Why is it assumed that vascular surgeons would/should take time out of their practice to answer the call without any additional compensation? If the compensation from these service lines is so lucrative, then compensation in the form of contracts needs to be offered to those who can provide the necessary services to treat the inevitable complications. This will in some way help compensate for time lost in the vascular surgeons’ practices.

The contracts should reflect the value to an institution vascular surgeons bring for their presence, including ED coverage for most if not all of the service lines, such as cardiology, radiology, orthopedics, gynecology, and general surgery. This also includes issues arising from the house staff inserting lines and from subsequent renal failure, as well as for angio-access patients who need immediate vascular backup to treat the vascular complications encountered.

In addition, these contracts should acknowledge the revenue generated by the presence of a vascular service line. With the burnout rate and unpredictable lifestyle, one would be concerned that vascular surgeons could be on the endangered species list; and given the current shortage of vascular surgeons, don’t our numbers reflect this concern?

There are no easy solutions because the field is a difficult one and is undercompensated for the risks assumed and services provided, which makes it an unattractive specialty, especially in today’s lifestyle-conscious generation. The vascular specialty is embattled, and the human toll extracted in the field speaks for itself. The rewards must improve to make things more appealing, and this will lead to an increase in the number of vascular surgeons, and more will join in groups to mitigate the effects of the stressors of the field. Until then, vascular surgeons need to demand that they receive fair compensation for their availability and the coverage they provide, which allows many other departments and specialties to function. This reality must be acknowledged and compensated.

Carlo A. Dall’Olmo, MD
Michigan Vascular Center
Flint, Michigan

Having taken the SVS “burnout” survey, I felt that it really never got into the “whys” of what was making individuals burn out. It dealt more with the consequences of the whys rather than the whys themselves, and it is these whys that must be addressed to assist in the prevention of burnout. I would like to comment on my experience of some, certainly not all, of the possible whys related to both inherent stressors and “administrator induced stressors” encountered in my 42-year vascular surgery practice that can easily cause burnout.

I believe there are several major areas that need to be evaluated to understand the causes of burnout because the complexities of today’s practice environment demand a different approach to the practice of vascular surgery for the well-being of the vascular surgeon. These complexities include the emotional baggage inherent in a practice, practice structure, unpredictable time management issues of running a practice, and hospital administration’s decisions creating unintended consequences for the vascular surgeon.

By its very nature, vascular surgery is a difficult field with many inherent stressors, endovascular innovations not withstanding. The initial emotional stressors may well be those of dealing with elderly patients with multiple severe comorbidities, poor outcomes, and the ensuing consequences. With the aging of the population, these stressors will only increase, yet compensation to treat these feeble patients has yet to rise to a level commensurate with the risk factors and complications the surgeon must deal with. Over time this will take its toll on some.

Which practice pattern one chooses to utilize – solo, group, or employed – also plays an important part. The presence or absence of appropriate help and backup for difficult cases, call coverage, and partnership financial packages can be either very stress producing or stress relieving. Are practice responsibilities and finances equally split so as to achieve a reasonable lifestyle, or is there a hierarchy of work and financial gain by which some must shoulder more of the burden for less pay than others? This is the beginning of the income versus lifestyle conflict and becomes a seriously stressful trap when one is short sighted and does not go for the long term. In our practice, we rotate the work and split the gain equally in return for the most valuable commodity of all: free time.

Time management is of paramount importance in completing a schedule, yet the paradox of the vascular world is its inherent unpredictability. There are difficult, time-consuming cases; unexpected, recurrent vascular problems in the same patient; urgent consults needing treatment within a few days; and the inevitable emergency room call for immediate treatment, day or night, for an embolism, vascular trauma, or ruptured aneurysm – not to mention the hospital committees or other responsibilities in the everyday life of a vascular surgeon.

One’s schedule requires dedicated time and attention yet the urgent/emergent issues interrupting one’s daily schedule ensures that the only predictability is unpredictability. This is a source of burnout. My experience over the years has been that about 25% of our practice load comes on an urgent to emergent basis, often causing considerable scheduling problems both in the operating room and at the office – again, issues that can cause tremendous stress for many. Without a large group, these constant stressors become difficult to shoulder.

Then there are the hospital-induced stressors caused by poorly conceived administrative decrees. One example is when emergency rooms need vascular services but no contracts are offered to secure these services, in which physicians are merely expected to provide 24/7 services. Once a physician has been called in for a case in the middle of the night, the stress of carrying on the next day becomes greater for that physician unless a system is in place for designated calls, which some larger groups have worked out.

Another example is the tendency to grant interventional privileges to those incapable of treating their operative complications without any consideration for who would reimburse those who come in after and how. Why is it assumed that vascular surgeons would/should take time out of their practice to answer the call without any additional compensation? If the compensation from these service lines is so lucrative, then compensation in the form of contracts needs to be offered to those who can provide the necessary services to treat the inevitable complications. This will in some way help compensate for time lost in the vascular surgeons’ practices.

The contracts should reflect the value to an institution vascular surgeons bring for their presence, including ED coverage for most if not all of the service lines, such as cardiology, radiology, orthopedics, gynecology, and general surgery. This also includes issues arising from the house staff inserting lines and from subsequent renal failure, as well as for angio-access patients who need immediate vascular backup to treat the vascular complications encountered.

In addition, these contracts should acknowledge the revenue generated by the presence of a vascular service line. With the burnout rate and unpredictable lifestyle, one would be concerned that vascular surgeons could be on the endangered species list; and given the current shortage of vascular surgeons, don’t our numbers reflect this concern?

There are no easy solutions because the field is a difficult one and is undercompensated for the risks assumed and services provided, which makes it an unattractive specialty, especially in today’s lifestyle-conscious generation. The vascular specialty is embattled, and the human toll extracted in the field speaks for itself. The rewards must improve to make things more appealing, and this will lead to an increase in the number of vascular surgeons, and more will join in groups to mitigate the effects of the stressors of the field. Until then, vascular surgeons need to demand that they receive fair compensation for their availability and the coverage they provide, which allows many other departments and specialties to function. This reality must be acknowledged and compensated.

Carlo A. Dall’Olmo, MD
Michigan Vascular Center
Flint, Michigan

Having taken the SVS “burnout” survey, I felt that it really never got into the “whys” of what was making individuals burn out. It dealt more with the consequences of the whys rather than the whys themselves, and it is these whys that must be addressed to assist in the prevention of burnout. I would like to comment on my experience of some, certainly not all, of the possible whys related to both inherent stressors and “administrator induced stressors” encountered in my 42-year vascular surgery practice that can easily cause burnout.

I believe there are several major areas that need to be evaluated to understand the causes of burnout because the complexities of today’s practice environment demand a different approach to the practice of vascular surgery for the well-being of the vascular surgeon. These complexities include the emotional baggage inherent in a practice, practice structure, unpredictable time management issues of running a practice, and hospital administration’s decisions creating unintended consequences for the vascular surgeon.

By its very nature, vascular surgery is a difficult field with many inherent stressors, endovascular innovations not withstanding. The initial emotional stressors may well be those of dealing with elderly patients with multiple severe comorbidities, poor outcomes, and the ensuing consequences. With the aging of the population, these stressors will only increase, yet compensation to treat these feeble patients has yet to rise to a level commensurate with the risk factors and complications the surgeon must deal with. Over time this will take its toll on some.

Which practice pattern one chooses to utilize – solo, group, or employed – also plays an important part. The presence or absence of appropriate help and backup for difficult cases, call coverage, and partnership financial packages can be either very stress producing or stress relieving. Are practice responsibilities and finances equally split so as to achieve a reasonable lifestyle, or is there a hierarchy of work and financial gain by which some must shoulder more of the burden for less pay than others? This is the beginning of the income versus lifestyle conflict and becomes a seriously stressful trap when one is short sighted and does not go for the long term. In our practice, we rotate the work and split the gain equally in return for the most valuable commodity of all: free time.

Time management is of paramount importance in completing a schedule, yet the paradox of the vascular world is its inherent unpredictability. There are difficult, time-consuming cases; unexpected, recurrent vascular problems in the same patient; urgent consults needing treatment within a few days; and the inevitable emergency room call for immediate treatment, day or night, for an embolism, vascular trauma, or ruptured aneurysm – not to mention the hospital committees or other responsibilities in the everyday life of a vascular surgeon.

One’s schedule requires dedicated time and attention yet the urgent/emergent issues interrupting one’s daily schedule ensures that the only predictability is unpredictability. This is a source of burnout. My experience over the years has been that about 25% of our practice load comes on an urgent to emergent basis, often causing considerable scheduling problems both in the operating room and at the office – again, issues that can cause tremendous stress for many. Without a large group, these constant stressors become difficult to shoulder.

Then there are the hospital-induced stressors caused by poorly conceived administrative decrees. One example is when emergency rooms need vascular services but no contracts are offered to secure these services, in which physicians are merely expected to provide 24/7 services. Once a physician has been called in for a case in the middle of the night, the stress of carrying on the next day becomes greater for that physician unless a system is in place for designated calls, which some larger groups have worked out.

Another example is the tendency to grant interventional privileges to those incapable of treating their operative complications without any consideration for who would reimburse those who come in after and how. Why is it assumed that vascular surgeons would/should take time out of their practice to answer the call without any additional compensation? If the compensation from these service lines is so lucrative, then compensation in the form of contracts needs to be offered to those who can provide the necessary services to treat the inevitable complications. This will in some way help compensate for time lost in the vascular surgeons’ practices.

The contracts should reflect the value to an institution vascular surgeons bring for their presence, including ED coverage for most if not all of the service lines, such as cardiology, radiology, orthopedics, gynecology, and general surgery. This also includes issues arising from the house staff inserting lines and from subsequent renal failure, as well as for angio-access patients who need immediate vascular backup to treat the vascular complications encountered.

In addition, these contracts should acknowledge the revenue generated by the presence of a vascular service line. With the burnout rate and unpredictable lifestyle, one would be concerned that vascular surgeons could be on the endangered species list; and given the current shortage of vascular surgeons, don’t our numbers reflect this concern?

There are no easy solutions because the field is a difficult one and is undercompensated for the risks assumed and services provided, which makes it an unattractive specialty, especially in today’s lifestyle-conscious generation. The vascular specialty is embattled, and the human toll extracted in the field speaks for itself. The rewards must improve to make things more appealing, and this will lead to an increase in the number of vascular surgeons, and more will join in groups to mitigate the effects of the stressors of the field. Until then, vascular surgeons need to demand that they receive fair compensation for their availability and the coverage they provide, which allows many other departments and specialties to function. This reality must be acknowledged and compensated.

Carlo A. Dall’Olmo, MD
Michigan Vascular Center
Flint, Michigan