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| The Covid Drug Wars That Pitted Doctor vs. Doctor | The Covid Drug Wars That Pitted Doctor vs. Doctor |
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| Mangala Narasimhan, an intensive-care-unit doctor, started feeling impatient soon after the start of a meeting she attended at Long Island Jewish Medical Center on May 13. She wanted to get back to the unit, but instead she was sitting in a conference room with about a dozen colleagues. By then, the surge of Covid-19 cases, the waves of suffering that had crashed down on her hospital for months, was beginning, miraculously, to recede. The throngs of out-of-town health care workers who had come to New York City to help were also diminishing, heading home to regions whose own times would come. Narasimhan and her team now had fewer hands to oversee new patients coming in and the long-suffering ones on ventilators who were still in need of meticulous care. Long Island Jewish, in Queens, had, at the time, treated more Covid-19 patients than any other hospital in the country; the doctors there were still weary, still battered, their energy and time in need of careful rationing. | Mangala Narasimhan, an intensive-care-unit doctor, started feeling impatient soon after the start of a meeting she attended at Long Island Jewish Medical Center on May 13. She wanted to get back to the unit, but instead she was sitting in a conference room with about a dozen colleagues. By then, the surge of Covid-19 cases, the waves of suffering that had crashed down on her hospital for months, was beginning, miraculously, to recede. The throngs of out-of-town health care workers who had come to New York City to help were also diminishing, heading home to regions whose own times would come. Narasimhan and her team now had fewer hands to oversee new patients coming in and the long-suffering ones on ventilators who were still in need of meticulous care. Long Island Jewish, in Queens, had, at the time, treated more Covid-19 patients than any other hospital in the country; the doctors there were still weary, still battered, their energy and time in need of careful rationing. |
| Narasimhan, who was in charge of more than 20 I.C.U.s across the Northwell Health system, knew heading into the meeting that it might be tense. Adey Tsegaye, a pulmonary-critical-care doctor who was calling in remotely, shared some of Narasimhan’s concerns. The meeting’s agenda included time for remarks from Alex Spyropoulos, a lead researcher at the Feinstein Institutes for Medical Research — the research arm of Northwell — who was running a clinical trial. The research was trying to determine whether a standard dose of an anticoagulant or a higher dose yielded better outcomes for Covid-19 patients who were already on oxygen or a ventilator and were at high risk of organ failure and clotting. | Narasimhan, who was in charge of more than 20 I.C.U.s across the Northwell Health system, knew heading into the meeting that it might be tense. Adey Tsegaye, a pulmonary-critical-care doctor who was calling in remotely, shared some of Narasimhan’s concerns. The meeting’s agenda included time for remarks from Alex Spyropoulos, a lead researcher at the Feinstein Institutes for Medical Research — the research arm of Northwell — who was running a clinical trial. The research was trying to determine whether a standard dose of an anticoagulant or a higher dose yielded better outcomes for Covid-19 patients who were already on oxygen or a ventilator and were at high risk of organ failure and clotting. |
| A doctor on Narasimhan’s unit had recently been at odds with a member of Spyropoulos’s research team. Stella Hahn, a pulmonary-critical-care doctor, arrived at work the day before the meeting to find that a Covid-19 patient had gone into cardiac arrest. She knew that the patient was enrolled in the clinical trial and had been randomly assigned to receive either the standard dose of the anticoagulant or the higher one. As is always the case in the most rigorous trials, neither the patient nor Hahn was supposed to know to which group this woman belonged. Double-blind, randomized, controlled trials — R.C.T.s — are considered the gold standard in research because they do not allow findings to be muddied by any individual doctor’s biases or assumptions. But Hahn believed that the patient’s condition now called for the higher dose, which could potentially require the patient’s removal from the trial. | A doctor on Narasimhan’s unit had recently been at odds with a member of Spyropoulos’s research team. Stella Hahn, a pulmonary-critical-care doctor, arrived at work the day before the meeting to find that a Covid-19 patient had gone into cardiac arrest. She knew that the patient was enrolled in the clinical trial and had been randomly assigned to receive either the standard dose of the anticoagulant or the higher one. As is always the case in the most rigorous trials, neither the patient nor Hahn was supposed to know to which group this woman belonged. Double-blind, randomized, controlled trials — R.C.T.s — are considered the gold standard in research because they do not allow findings to be muddied by any individual doctor’s biases or assumptions. But Hahn believed that the patient’s condition now called for the higher dose, which could potentially require the patient’s removal from the trial. |
| Word made it back to a doctor working with Spyropoulos, and that doctor called Hahn to urge her to reconsider, or at least to get more tests before acting. They exchanged heated words, as the colleague implored her to stay the course. Hahn pushed back: She had to rely on her clinical judgment and believed that it was unethical to wait for more information. How could researchers dictate care to a doctor right there at the bedside, especially when a patient’s condition was so dire? | Word made it back to a doctor working with Spyropoulos, and that doctor called Hahn to urge her to reconsider, or at least to get more tests before acting. They exchanged heated words, as the colleague implored her to stay the course. Hahn pushed back: She had to rely on her clinical judgment and believed that it was unethical to wait for more information. How could researchers dictate care to a doctor right there at the bedside, especially when a patient’s condition was so dire? |
| The point of contention would be discussed at the May 13 meeting. Dozens of doctors from the Northwell system videoconferenced in, including Spyropoulos, who was seated in his home in Westchester. Hahn’s colleagues, a tightknit unit who had seen one another through so much, sat together in the conference room, occasionally checking their phones or exchanging glances as the meeting went on. As Spyropoulos recalls, he talked to the group about the importance of high-quality, randomized trials in making scientific progress, and the risks of trying experimental treatments without them. “I stressed to the group that we should not abandon this principle, even in the very stressful environment of a pandemic that was overwhelming our hospitals at Northwell,” he said. Relying on gut instinct rather than evidence, he told them, was essentially “witchcraft.” | The point of contention would be discussed at the May 13 meeting. Dozens of doctors from the Northwell system videoconferenced in, including Spyropoulos, who was seated in his home in Westchester. Hahn’s colleagues, a tightknit unit who had seen one another through so much, sat together in the conference room, occasionally checking their phones or exchanging glances as the meeting went on. As Spyropoulos recalls, he talked to the group about the importance of high-quality, randomized trials in making scientific progress, and the risks of trying experimental treatments without them. “I stressed to the group that we should not abandon this principle, even in the very stressful environment of a pandemic that was overwhelming our hospitals at Northwell,” he said. Relying on gut instinct rather than evidence, he told them, was essentially “witchcraft.” |
| For Tsegaye, the word landed like a blow. “There was a chill in the air,” said Tsegaye, who registered it even by videoconference. “Followed by rapid backpedaling.” Spyropoulos quickly explained that he had so much respect for what those doctors had done — he had not been in those critical-care units, in the emergency room, which he knew were unlike any other he had ever experienced. “But it was like a retraction sent to the newspaper the next day,” Tsegaye said. “The headline says it all. The retraction the next day? It doesn’t have the same impact.” | For Tsegaye, the word landed like a blow. “There was a chill in the air,” said Tsegaye, who registered it even by videoconference. “Followed by rapid backpedaling.” Spyropoulos quickly explained that he had so much respect for what those doctors had done — he had not been in those critical-care units, in the emergency room, which he knew were unlike any other he had ever experienced. “But it was like a retraction sent to the newspaper the next day,” Tsegaye said. “The headline says it all. The retraction the next day? It doesn’t have the same impact.” |
| In the days to come, whenever Tsegaye thought about what Spyropoulos said in that meeting, she felt appalled all over again. She knew that she had never extended herself on behalf of her patients the way she had since March. She kept flashing back to a day when she was told that a ventilated patient’s endotracheal tube had fallen out, a situation that can be fatal for the patient and is also dangerous for the physician: Replacing it requires the doctor to come into close contact with the patient’s breath. Tsegaye was putting on her N95 mask to enter the patient’s room when its elastic snapped in two. There was no time to go to the supply area to get a new mask. What was the right thing to do? With a sense of dread, she found her feet and moved toward the patient’s room. As she prepared to enter, one of her fellows, whose mask was intact, told her to leave — she could manage it on her own. | In the days to come, whenever Tsegaye thought about what Spyropoulos said in that meeting, she felt appalled all over again. She knew that she had never extended herself on behalf of her patients the way she had since March. She kept flashing back to a day when she was told that a ventilated patient’s endotracheal tube had fallen out, a situation that can be fatal for the patient and is also dangerous for the physician: Replacing it requires the doctor to come into close contact with the patient’s breath. Tsegaye was putting on her N95 mask to enter the patient’s room when its elastic snapped in two. There was no time to go to the supply area to get a new mask. What was the right thing to do? With a sense of dread, she found her feet and moved toward the patient’s room. As she prepared to enter, one of her fellows, whose mask was intact, told her to leave — she could manage it on her own. |
| Looking back, Tsegaye felt that the agony of making those kinds of decisions all day long compounded the grief she felt while treating so many patients she could not help. “These are the decisions we have had to face,” Tsegaye said. “For someone like me, who had been in that situation, to have someone tell you that you have been practicing witchcraft is kind of giving no value to the sacrifice that I have made — that my colleagues have made.” | Looking back, Tsegaye felt that the agony of making those kinds of decisions all day long compounded the grief she felt while treating so many patients she could not help. “These are the decisions we have had to face,” Tsegaye said. “For someone like me, who had been in that situation, to have someone tell you that you have been practicing witchcraft is kind of giving no value to the sacrifice that I have made — that my colleagues have made.” |
| As doctors face new spikes of Covid-19 cases around the country, they are also confronting a harsh reality: The virus’s deadly secrets remain largely intact. The medical community now has some research-backed drug treatments — remdesivir, an antiviral drug found to shorten hospital stays, and dexamethasone, a cheap, readily available steroid that seems to cut deaths of patients on ventilators by a third. But six months after the first patient tested positive on the West Coast, there is still no treatment that reliably slows progression of the illness, much less a cure. In July, the number of patients dying in this country topped 1,000 five days in a row, according to the Covid Tracking Project. | As doctors face new spikes of Covid-19 cases around the country, they are also confronting a harsh reality: The virus’s deadly secrets remain largely intact. The medical community now has some research-backed drug treatments — remdesivir, an antiviral drug found to shorten hospital stays, and dexamethasone, a cheap, readily available steroid that seems to cut deaths of patients on ventilators by a third. But six months after the first patient tested positive on the West Coast, there is still no treatment that reliably slows progression of the illness, much less a cure. In July, the number of patients dying in this country topped 1,000 five days in a row, according to the Covid Tracking Project. |
| In these early months, doctors have faced two unknowns in trying to fight the devastation. The first is the virus itself: deadly, contagious and entirely novel. The standard of care for most intractable illnesses develops over years, as doctors build a body of research that tests various theories, compares and contrasts dosages, measures one drug’s power against another. Here doctors were starting from scratch: Any treatment protocol beyond supportive care — oxygen, hydration, antibiotics and ventilation — was conjecture. The second, equally novel challenge has been the sheer scale of the outbreak. Few doctors in this country had encountered the overwhelming volume of patients, the sense of helplessness, the exhaustion and the desperation to save lives. Hospital administrators found themselves plunging headlong into making difficult decisions in the absence of strong, unifying federal guidance. Most did so without the benefit of perfectly parallel case studies or personal experience in hospitals so overrun by suffering. | In these early months, doctors have faced two unknowns in trying to fight the devastation. The first is the virus itself: deadly, contagious and entirely novel. The standard of care for most intractable illnesses develops over years, as doctors build a body of research that tests various theories, compares and contrasts dosages, measures one drug’s power against another. Here doctors were starting from scratch: Any treatment protocol beyond supportive care — oxygen, hydration, antibiotics and ventilation — was conjecture. The second, equally novel challenge has been the sheer scale of the outbreak. Few doctors in this country had encountered the overwhelming volume of patients, the sense of helplessness, the exhaustion and the desperation to save lives. Hospital administrators found themselves plunging headlong into making difficult decisions in the absence of strong, unifying federal guidance. Most did so without the benefit of perfectly parallel case studies or personal experience in hospitals so overrun by suffering. |
| When there is no precedent, when there is an information vacuum, decisions are inevitably subject to challenge. In an already heated environment, some of the worst of the tensions played out between research-oriented doctors and those who saw themselves primarily as clinicians. Many treating patients on the floor considered it axiomatic that, with so many dying so fast and so little to go on, they would rely on their experience to make judgment calls about treatment options. They would try using medications that had been approved for other illnesses but not yet for this one — what the medical community calls off-label uses — if they felt they had good reasons to do so. They would take into consideration any information that was available: the observations of doctors in Milan and China, conversations among doctors in WhatsApp group texts and in Covid-19 physician Facebook groups, tidbits of research that made medical sense but had not yet been peer-reviewed. | When there is no precedent, when there is an information vacuum, decisions are inevitably subject to challenge. In an already heated environment, some of the worst of the tensions played out between research-oriented doctors and those who saw themselves primarily as clinicians. Many treating patients on the floor considered it axiomatic that, with so many dying so fast and so little to go on, they would rely on their experience to make judgment calls about treatment options. They would try using medications that had been approved for other illnesses but not yet for this one — what the medical community calls off-label uses — if they felt they had good reasons to do so. They would take into consideration any information that was available: the observations of doctors in Milan and China, conversations among doctors in WhatsApp group texts and in Covid-19 physician Facebook groups, tidbits of research that made medical sense but had not yet been peer-reviewed. |
| Other clinicians, and especially doctors more heavily involved in research, were frustrated that many of their colleagues were not sufficiently invested in the importance of empirical research to figure out which treatments worked best and were safest. Kevin Tracey, president of the Feinstein Institutes, tried to emphasize to the doctors affiliated with the Northwell hospital system that if they were going to try drugs off-label, they should always be doing so in the context of a clinical research trial: The drug might help some patients but could hurt even more of them. If that was the case, it was better to know than to operate out of a mix of hope and conviction. He understood, he said, the impulse for doctors to try drugs off-label out of compassion — and the “raw emotion of humans trying to help each other survive and not knowing what to do.” But he did not approve of it. “Emotions cannot carry the day,” he said. “You need evidence-based medicine, and you need clinical trials. You don’t make an exception in the middle of a pandemic.” | Other clinicians, and especially doctors more heavily involved in research, were frustrated that many of their colleagues were not sufficiently invested in the importance of empirical research to figure out which treatments worked best and were safest. Kevin Tracey, president of the Feinstein Institutes, tried to emphasize to the doctors affiliated with the Northwell hospital system that if they were going to try drugs off-label, they should always be doing so in the context of a clinical research trial: The drug might help some patients but could hurt even more of them. If that was the case, it was better to know than to operate out of a mix of hope and conviction. He understood, he said, the impulse for doctors to try drugs off-label out of compassion — and the “raw emotion of humans trying to help each other survive and not knowing what to do.” But he did not approve of it. “Emotions cannot carry the day,” he said. “You need evidence-based medicine, and you need clinical trials. You don’t make an exception in the middle of a pandemic.” |
| Ethan Weiss, a cardiologist at the University of California, San Francisco, who specializes in metabolic research, spent two weeks treating patients at a hospital in New York and was also distressed by how quickly doctors were trying untested therapies outside clinical trials. “I mean, it felt like it wasn’t even World War I medicine,” he said. “It was almost like Civil War-level medicine.” He asked that the name of that New York hospital be withheld out of respect for his colleagues, whom he knows were not only risking their lives but were also overwhelmed by their clinical demands and had no research to rely on. He nonetheless was surprised to see many of them making decisions “based on the sort of opinion or written protocol of one or a couple of people that was based on kind of nothing that I could see, other than just, ‘This seems like a good idea.’” | Ethan Weiss, a cardiologist at the University of California, San Francisco, who specializes in metabolic research, spent two weeks treating patients at a hospital in New York and was also distressed by how quickly doctors were trying untested therapies outside clinical trials. “I mean, it felt like it wasn’t even World War I medicine,” he said. “It was almost like Civil War-level medicine.” He asked that the name of that New York hospital be withheld out of respect for his colleagues, whom he knows were not only risking their lives but were also overwhelmed by their clinical demands and had no research to rely on. He nonetheless was surprised to see many of them making decisions “based on the sort of opinion or written protocol of one or a couple of people that was based on kind of nothing that I could see, other than just, ‘This seems like a good idea.’” |
| Many clinicians on the ground felt the urgency of treating the hundreds of patients dying in front of them; researchers, with their literal and intellectual distance from the I.C.U., were pressing them to think about the thousands of patients who were sure to follow — to slow down long enough to build a body of evidence that they knew with more certainty could help. The tensions between these two ways of thinking about medicine have always existed. But during the early months of the pandemic, the disagreements — what one critical-care doctor called, on his well-read blog, the profession’s “intellectual food fight” — provided another layer of painful stress to some doctors already near their limits. “It became like Republicans and Democrats,” said Pierre Kory, a critical-care doctor who faced that tension himself at the University of Wisconsin Hospital and Clinics. “The two sides can’t talk to each other.” | Many clinicians on the ground felt the urgency of treating the hundreds of patients dying in front of them; researchers, with their literal and intellectual distance from the I.C.U., were pressing them to think about the thousands of patients who were sure to follow — to slow down long enough to build a body of evidence that they knew with more certainty could help. The tensions between these two ways of thinking about medicine have always existed. But during the early months of the pandemic, the disagreements — what one critical-care doctor called, on his well-read blog, the profession’s “intellectual food fight” — provided another layer of painful stress to some doctors already near their limits. “It became like Republicans and Democrats,” said Pierre Kory, a critical-care doctor who faced that tension himself at the University of Wisconsin Hospital and Clinics. “The two sides can’t talk to each other.” |
| As they prepare to evaluate a given medication or procedure, researchers are expected to approach their task with a certain neutral mind-set. The official term for that stance sounds both scientific and strangely poetic: “clinical equipoise.” It’s a point at which a doctor’s curiosity is greater than her conviction that any one result is the most likely one. Clinical equipoise is an elegant characterization of a humble admission: I have no idea which of these two choices is better. | As they prepare to evaluate a given medication or procedure, researchers are expected to approach their task with a certain neutral mind-set. The official term for that stance sounds both scientific and strangely poetic: “clinical equipoise.” It’s a point at which a doctor’s curiosity is greater than her conviction that any one result is the most likely one. Clinical equipoise is an elegant characterization of a humble admission: I have no idea which of these two choices is better. |
| Equipoise gave way to unbridled enthusiasm among some physicians at Lenox Hill Hospital on the Upper East Side of New York in April when the city was in the thick of the surge. Many doctors there believed they were seeing great results by providing tocilizumab, an anti-inflammatory drug that tamps down the autoimmune response and is used for rheumatoid arthritis. The doctors were prescribing the drug, sometimes in conjunction with a steroid, to Covid-19 patients, particularly those who were not yet on ventilators but whose blood tests suggested that they were about to take a turn for the worse. In using it, doctors hoped to stave off what’s known as a cytokine storm, a potentially deadly immune-system overreaction in which a torrent of cytokines — proteins that can trigger infection-fighting forces — is released. Tocilizumab, which blocks the pathway of a cytokine called IL-6, might prevent that deadly storm from gathering force. But any anti-inflammatory carries risk, because in fighting inflammation, it can also hamper the body’s ability to clear the primary infection or others that follow; tocilizumab is also thought to carry some elevated risk of anaphylactic shock and lower-intestinal perforation. | Equipoise gave way to unbridled enthusiasm among some physicians at Lenox Hill Hospital on the Upper East Side of New York in April when the city was in the thick of the surge. Many doctors there believed they were seeing great results by providing tocilizumab, an anti-inflammatory drug that tamps down the autoimmune response and is used for rheumatoid arthritis. The doctors were prescribing the drug, sometimes in conjunction with a steroid, to Covid-19 patients, particularly those who were not yet on ventilators but whose blood tests suggested that they were about to take a turn for the worse. In using it, doctors hoped to stave off what’s known as a cytokine storm, a potentially deadly immune-system overreaction in which a torrent of cytokines — proteins that can trigger infection-fighting forces — is released. Tocilizumab, which blocks the pathway of a cytokine called IL-6, might prevent that deadly storm from gathering force. But any anti-inflammatory carries risk, because in fighting inflammation, it can also hamper the body’s ability to clear the primary infection or others that follow; tocilizumab is also thought to carry some elevated risk of anaphylactic shock and lower-intestinal perforation. |
| Patients with extreme flu in the I.C.U. sometimes received tocilizumab; it is also used to treat cytokine storms that some cancer patients experience as a side effect of treatment. Doctors at Lenox Hill did not believe it was a leap to think that the drug could address cytokine storms in Covid-19 patients. They knew that doctors in Milan were leaning heavily on the drug; they were in conversation with doctors at Yale New Haven Health, considered a fortress of research-heavy medicine, which also incorporated tocilizumab into their protocol. In addition, some small studies showed support for the drug’s effectiveness, though none were randomized, controlled trials. | Patients with extreme flu in the I.C.U. sometimes received tocilizumab; it is also used to treat cytokine storms that some cancer patients experience as a side effect of treatment. Doctors at Lenox Hill did not believe it was a leap to think that the drug could address cytokine storms in Covid-19 patients. They knew that doctors in Milan were leaning heavily on the drug; they were in conversation with doctors at Yale New Haven Health, considered a fortress of research-heavy medicine, which also incorporated tocilizumab into their protocol. In addition, some small studies showed support for the drug’s effectiveness, though none were randomized, controlled trials. |
| “I understand that it has never been trialed,” John Boockvar, a neurosurgeon at Lenox Hill who is affiliated with the Feinstein Institutes, told me in late April. (Boockvar is one of the doctors featured on the documentary series “Lenox Hill.”) “But there is clearly enough data to support its use.” The doctors at Lenox Hill had also briefly participated in a randomized, controlled trial for another drug with a similar mechanism, called sarilumab. But to Boockvar, enrolling a patient in that trial, which might result in a patient receiving a placebo, posed an ethical challenge when he could simply prescribe tocilizumab — doctors refer to it as toci — instead. In April, he learned that Massachusetts General Hospital was starting a randomized, controlled trial for tocilizumab. “If that was my loved one,” he said, imagining a family member who might receive a placebo in that trial, “I’d be upset. I’d think, Why am I doing this? If it’s an off-label use with an approved drug — give the damn drug to everybody.” | “I understand that it has never been trialed,” John Boockvar, a neurosurgeon at Lenox Hill who is affiliated with the Feinstein Institutes, told me in late April. (Boockvar is one of the doctors featured on the documentary series “Lenox Hill.”) “But there is clearly enough data to support its use.” The doctors at Lenox Hill had also briefly participated in a randomized, controlled trial for another drug with a similar mechanism, called sarilumab. But to Boockvar, enrolling a patient in that trial, which might result in a patient receiving a placebo, posed an ethical challenge when he could simply prescribe tocilizumab — doctors refer to it as toci — instead. In April, he learned that Massachusetts General Hospital was starting a randomized, controlled trial for tocilizumab. “If that was my loved one,” he said, imagining a family member who might receive a placebo in that trial, “I’d be upset. I’d think, Why am I doing this? If it’s an off-label use with an approved drug — give the damn drug to everybody.” |
| At Long Island Jewish, some doctors who were hearing about the drug from colleagues at Lenox Hill, a part of the Northwell Health consortium, started clamoring for liberal access to it. And yet sometimes, when doctors placed orders with the hospital pharmacist, their prescriptions were declined; those patients didn’t meet criteria Northwell had established for administering tocilizumab, which was in short supply. Physicians were frustrated that patients who they believed would benefit from the drug could not receive it. Northwell wanted to be conservative about the off-label use of drugs outside clinical trials. “There’s no proof that anything works!” Tsegaye thought at the time. “Everything is experimental!” As for enrolling patients in a trial, as overwhelmed as she was, she hardly felt she was in a position to take that on. | At Long Island Jewish, some doctors who were hearing about the drug from colleagues at Lenox Hill, a part of the Northwell Health consortium, started clamoring for liberal access to it. And yet sometimes, when doctors placed orders with the hospital pharmacist, their prescriptions were declined; those patients didn’t meet criteria Northwell had established for administering tocilizumab, which was in short supply. Physicians were frustrated that patients who they believed would benefit from the drug could not receive it. Northwell wanted to be conservative about the off-label use of drugs outside clinical trials. “There’s no proof that anything works!” Tsegaye thought at the time. “Everything is experimental!” As for enrolling patients in a trial, as overwhelmed as she was, she hardly felt she was in a position to take that on. |
| Tsegaye’s supervisor, Narasimhan, also knew researchers were concerned that in prescribing tocilizumab so readily, physicians were possibly hampering enrollment in the trial underway at her hospital for sarilumab — a patient who received tocilizumab could not also receive sarilumab. She and her team did not prioritize the trials, she said; they wanted to provide the drugs they thought were needed. “We’ve always been allowed to choose treatment, right or wrong, based on what we thought was best,” Narasimhan said in May. “And that was gone. It was hard.” | Tsegaye’s supervisor, Narasimhan, also knew researchers were concerned that in prescribing tocilizumab so readily, physicians were possibly hampering enrollment in the trial underway at her hospital for sarilumab — a patient who received tocilizumab could not also receive sarilumab. She and her team did not prioritize the trials, she said; they wanted to provide the drugs they thought were needed. “We’ve always been allowed to choose treatment, right or wrong, based on what we thought was best,” Narasimhan said in May. “And that was gone. It was hard.” |
| In addition to fighting resistance from their administrators, the doctors were sometimes also at odds with their colleagues, especially infectious-disease doctors, many of whom believed that anti-inflammatories like tocilizumab and steroids could do more harm than good. “You’re killing these patients,” one infectious-disease doctor told Hahn at Long Island Jewish. | In addition to fighting resistance from their administrators, the doctors were sometimes also at odds with their colleagues, especially infectious-disease doctors, many of whom believed that anti-inflammatories like tocilizumab and steroids could do more harm than good. “You’re killing these patients,” one infectious-disease doctor told Hahn at Long Island Jewish. |
| In the Mount Sinai Health System, tocilizumab was also in demand. Administrators felt the stress of making decisions in the absence of clear data. Judith Aberg, the chief of the division of infectious diseases for Mount Sinai, fielded demands from doctors working on wards who wanted to use tocilizumab, early and often. “I have to give her credit; she was single-handedly fighting off a lot of pressure from hematologists,” said Keren Osman, a Mount Sinai oncologist and hematologist who was on some of those calls. As experts in blood cancers and diseases, hematologists had experience working with tocilizumab to treat cytokine storms that were a side effect of some cancer treatments. “She was saying, ‘I’m not comfortable just giving patients willy-nilly anything we have — we don’t know.’” | In the Mount Sinai Health System, tocilizumab was also in demand. Administrators felt the stress of making decisions in the absence of clear data. Judith Aberg, the chief of the division of infectious diseases for Mount Sinai, fielded demands from doctors working on wards who wanted to use tocilizumab, early and often. “I have to give her credit; she was single-handedly fighting off a lot of pressure from hematologists,” said Keren Osman, a Mount Sinai oncologist and hematologist who was on some of those calls. As experts in blood cancers and diseases, hematologists had experience working with tocilizumab to treat cytokine storms that were a side effect of some cancer treatments. “She was saying, ‘I’m not comfortable just giving patients willy-nilly anything we have — we don’t know.’” |
| Patients and their families, who heard through the news media about the drug, also started to demand it, even for Covid-19 patients whose inflammatory markers were normal. “People were calling for us to give it, just to give it, because there were no other therapies,” Aberg said. At first, a medical team that included Aberg agreed to put some patients who were on ventilators on the drug — in those patients, it was obvious that systemic inflammation was already evident; also, the closer the patient was to dying, the more the risk seemed justified. Eventually, the thinking at Aberg’s hospitals and at others evolved to favor use of the drug earlier, before systemic inflammation did so much damage that the patient was already clinging to life. | Patients and their families, who heard through the news media about the drug, also started to demand it, even for Covid-19 patients whose inflammatory markers were normal. “People were calling for us to give it, just to give it, because there were no other therapies,” Aberg said. At first, a medical team that included Aberg agreed to put some patients who were on ventilators on the drug — in those patients, it was obvious that systemic inflammation was already evident; also, the closer the patient was to dying, the more the risk seemed justified. Eventually, the thinking at Aberg’s hospitals and at others evolved to favor use of the drug earlier, before systemic inflammation did so much damage that the patient was already clinging to life. |
| By May, doctors at Long Island Jewish and Mount Sinai had stopped pressing for tocilizumab — if it was effective, it was not such a miracle drug that they could see its effects clearly. Many had started to pin their hopes instead on convalescent plasma, another experimental treatment in which sick patients are given plasma from recovered patients with antibodies, though its effectiveness is still unknown. “We did rush,” Aberg says now. “I mean, we were pushed. We were grasping for anything that we could possibly do.” | By May, doctors at Long Island Jewish and Mount Sinai had stopped pressing for tocilizumab — if it was effective, it was not such a miracle drug that they could see its effects clearly. Many had started to pin their hopes instead on convalescent plasma, another experimental treatment in which sick patients are given plasma from recovered patients with antibodies, though its effectiveness is still unknown. “We did rush,” Aberg says now. “I mean, we were pushed. We were grasping for anything that we could possibly do.” |
| In early July, the drug company studying sarilumab, the drug similar to tocilizumab, announced that it was halting its trial; researchers found, as Aberg put it, “nada.” A few weeks later, the pharmaceutical company Roche announced preliminary results of a tocilizumab trial that was run on Covid patients with pneumonia. The drug’s effects were no better than a placebo. By then, Narasimhan was also starting to see preliminary reports of other research that showed the drug could, in fact, be dangerous, increasing the risk of fatal secondary and fungal infections. | In early July, the drug company studying sarilumab, the drug similar to tocilizumab, announced that it was halting its trial; researchers found, as Aberg put it, “nada.” A few weeks later, the pharmaceutical company Roche announced preliminary results of a tocilizumab trial that was run on Covid patients with pneumonia. The drug’s effects were no better than a placebo. By then, Narasimhan was also starting to see preliminary reports of other research that showed the drug could, in fact, be dangerous, increasing the risk of fatal secondary and fungal infections. |
| “My take-home is that I wish we had done more randomized, controlled trials so we could have some real answers, so that we could tell Florida and Texas, ‘This works, and this doesn’t work,’” Narasimhan, who is now in charge of intensive-care units throughout the Northwell Health system, told me in July. “We could have had so many more answers in a way that was meaningful. We had this fixation that all these drugs were curative. And they weren’t.” | “My take-home is that I wish we had done more randomized, controlled trials so we could have some real answers, so that we could tell Florida and Texas, ‘This works, and this doesn’t work,’” Narasimhan, who is now in charge of intensive-care units throughout the Northwell Health system, told me in July. “We could have had so many more answers in a way that was meaningful. We had this fixation that all these drugs were curative. And they weren’t.” |
| The story of hydroxychloroquine will most likely be recalled as a classic medical parable of the pandemic. It was a drug that seemed so promising that physicians were desperate to use it, and researchers were equally driven to see if it actually delivered the hoped-for results. In the end, the enthusiasm of the first camp most likely slowed the speed with which the second could study the drug — only to find that the enthusiasm was never really justified in the first place. | The story of hydroxychloroquine will most likely be recalled as a classic medical parable of the pandemic. It was a drug that seemed so promising that physicians were desperate to use it, and researchers were equally driven to see if it actually delivered the hoped-for results. In the end, the enthusiasm of the first camp most likely slowed the speed with which the second could study the drug — only to find that the enthusiasm was never really justified in the first place. |
| In mid-March, Steven Libutti, director of the Rutgers Cancer Institute of New Jersey, read about a small hydroxychloroquine trial in France that was generating attention, having found that the anti-malarial might be effective in the treatment of Covid-19. “It looked interesting, exciting, promising, but it looked very far from convincing,” Libutti said. Although his specialty is cancer, he wanted to bring his extensive research knowledge to bear on the pressing question of the drug’s effectiveness. He wrote a proposal for a randomized, controlled trial that would measure the effectiveness of hydroxychloroquine on a patient’s viral load. (He was comparing the effect of the drug alone with placebo, as well as with the drug when administered with another drug called azithromycin.) | In mid-March, Steven Libutti, director of the Rutgers Cancer Institute of New Jersey, read about a small hydroxychloroquine trial in France that was generating attention, having found that the anti-malarial might be effective in the treatment of Covid-19. “It looked interesting, exciting, promising, but it looked very far from convincing,” Libutti said. Although his specialty is cancer, he wanted to bring his extensive research knowledge to bear on the pressing question of the drug’s effectiveness. He wrote a proposal for a randomized, controlled trial that would measure the effectiveness of hydroxychloroquine on a patient’s viral load. (He was comparing the effect of the drug alone with placebo, as well as with the drug when administered with another drug called azithromycin.) |
| The Food and Drug Administration and the ethical review board at the Rutgers Cancer Institute approved his trial in record time, as has been typical for many proposed drug trials during the pandemic. He enrolled the first patient on April 1, hoping he could easily reach 150, calling on doctors to recruit patients at six hospitals in New Jersey. | The Food and Drug Administration and the ethical review board at the Rutgers Cancer Institute approved his trial in record time, as has been typical for many proposed drug trials during the pandemic. He enrolled the first patient on April 1, hoping he could easily reach 150, calling on doctors to recruit patients at six hospitals in New Jersey. |
| By then President Trump had claimed in mid-March that the drug was a “game changer.” Some doctors in New York were quietly taking it prophylactically. That month, the F.D.A. authorized hydroxychloroquine for emergency use, a special dispensation that facilitated doctors’ access to the drug even outside the context of a trial. Many New York hospitals’ standard treatment protocols encouraged doctors to consider hydroxychloroquine for patients, even though the evidence that it worked remained slim and reports were emerging that in some patients it was causing heart problems. | By then President Trump had claimed in mid-March that the drug was a “game changer.” Some doctors in New York were quietly taking it prophylactically. That month, the F.D.A. authorized hydroxychloroquine for emergency use, a special dispensation that facilitated doctors’ access to the drug even outside the context of a trial. Many New York hospitals’ standard treatment protocols encouraged doctors to consider hydroxychloroquine for patients, even though the evidence that it worked remained slim and reports were emerging that in some patients it was causing heart problems. |
| Thousands of patients were pouring through those six New Jersey hospitals, but Libutti waited, for weeks, with great frustration as only a handful of patients were enrolled in his trial each day. Typically, in clinical trials, after a patient is admitted to the hospital, a doctor or nurse, often affiliated with the research, talks to the patient about the possibility of enrolling in a clinical trial. But Libutti’s team was finding that by the time a nurse could begin the conversation with the patient, that person had already been administered hydroxychloroquine — which meant the researchers could not get a baseline reading of that patient’s viral load. Patient after patient was disqualified from the study. They had “been handed hydroxychloroquine along with their toothbrush and slippers when they got to the emergency room,” Libutti told me. “They were giving it out like dinner mints.” The researcher said he “was shocked by the number of folks whom I thought were incredibly well-read, knowledgeable physicians but were just panic-prescribing hydroxychloroquine. I’ve never seen anything like it. It just shows how lost in the storm folks were.” (Michael Steinberg, who helps oversee trials as well as clinical care at Robert Wood Johnson University Hospital, which was involved in Libutti’s trial, said that although physicians use their clinical judgment to make decisions about treatment, they strongly encourage doctors to use evidence-based criteria.) | Thousands of patients were pouring through those six New Jersey hospitals, but Libutti waited, for weeks, with great frustration as only a handful of patients were enrolled in his trial each day. Typically, in clinical trials, after a patient is admitted to the hospital, a doctor or nurse, often affiliated with the research, talks to the patient about the possibility of enrolling in a clinical trial. But Libutti’s team was finding that by the time a nurse could begin the conversation with the patient, that person had already been administered hydroxychloroquine — which meant the researchers could not get a baseline reading of that patient’s viral load. Patient after patient was disqualified from the study. They had “been handed hydroxychloroquine along with their toothbrush and slippers when they got to the emergency room,” Libutti told me. “They were giving it out like dinner mints.” The researcher said he “was shocked by the number of folks whom I thought were incredibly well-read, knowledgeable physicians but were just panic-prescribing hydroxychloroquine. I’ve never seen anything like it. It just shows how lost in the storm folks were.” (Michael Steinberg, who helps oversee trials as well as clinical care at Robert Wood Johnson University Hospital, which was involved in Libutti’s trial, said that although physicians use their clinical judgment to make decisions about treatment, they strongly encourage doctors to use evidence-based criteria.) |
| Other doctors shared Libutti’s experience. Arthur Caplan, a bioethicist at New York University’s medical school, said he is aware of three medical centers where researchers trying to study hydroxychloroquine felt that the early ardor for the drug among doctors and patients made it difficult for them to recruit subjects — to determine, essentially, whether the embrace of the drug was at all justified. Caplan and a colleague argued, in an article published online in April in The Journal of Clinical Investigation, that “panicked rhetoric about right-to-try must be aggressively discouraged in order for scientists to learn what regimens or vaccines actually work.” Communicating directly with doctors at various hospitals who were making the drug part of the official protocol, he used more plain language: “This is nuts!” | Other doctors shared Libutti’s experience. Arthur Caplan, a bioethicist at New York University’s medical school, said he is aware of three medical centers where researchers trying to study hydroxychloroquine felt that the early ardor for the drug among doctors and patients made it difficult for them to recruit subjects — to determine, essentially, whether the embrace of the drug was at all justified. Caplan and a colleague argued, in an article published online in April in The Journal of Clinical Investigation, that “panicked rhetoric about right-to-try must be aggressively discouraged in order for scientists to learn what regimens or vaccines actually work.” Communicating directly with doctors at various hospitals who were making the drug part of the official protocol, he used more plain language: “This is nuts!” |
| The Montefiore Health System in New York was one of the many that included hydroxychloroquine as an option in its treatment protocol, starting in late March. Michelle Ng Gong, the director of critical-care research, did not actively fight to have the drug removed from the protocol. But when she was working in her capacity as a critical-care doctor, she does not recall ever prescribing the medication, and she sometimes took patients who had received it in the emergency room off it. “When so many people are dying, you want to do something,” she said. But very sick patients are more susceptible to adverse events. “The problem is that we know from critical-care literature, as well as trials in the past, that we can always do more harm.” | The Montefiore Health System in New York was one of the many that included hydroxychloroquine as an option in its treatment protocol, starting in late March. Michelle Ng Gong, the director of critical-care research, did not actively fight to have the drug removed from the protocol. But when she was working in her capacity as a critical-care doctor, she does not recall ever prescribing the medication, and she sometimes took patients who had received it in the emergency room off it. “When so many people are dying, you want to do something,” she said. But very sick patients are more susceptible to adverse events. “The problem is that we know from critical-care literature, as well as trials in the past, that we can always do more harm.” |
| In the end, the biggest randomized, controlled trial on hydroxychloroquine came out of Britain in June, and preliminary results found that the drug was not an effective treatment for Covid-19. In contrast to American doctors whose access to the use of the drug, even outside trials, had been eased by a federal agency, British physicians were given the opposite message. On April 1, the highest medical officials in England, Wales, Northern Ireland and Scotland each sent a letter to every hospital in their respective countries, urging doctors not to prescribe medications off-label outside trials. Instead they encouraged doctors to enroll their patients in large, multicenter, randomized, controlled trials, like a study run by the University of Oxford called Recovery, which looked at the efficacy of hydroxychloroquine, tocilizumab, convalescent plasma, dexamethasone and two other treatments. At some hospitals in Britain, as many as about 60 percent of patients were enrolled in Recovery trials; even the Northwell system, which is committed to research, was able to enroll, at its most trial-driven hospital, North Shore University Hospital, around only 20 percent of its patients in clinical trials. | In the end, the biggest randomized, controlled trial on hydroxychloroquine came out of Britain in June, and preliminary results found that the drug was not an effective treatment for Covid-19. In contrast to American doctors whose access to the use of the drug, even outside trials, had been eased by a federal agency, British physicians were given the opposite message. On April 1, the highest medical officials in England, Wales, Northern Ireland and Scotland each sent a letter to every hospital in their respective countries, urging doctors not to prescribe medications off-label outside trials. Instead they encouraged doctors to enroll their patients in large, multicenter, randomized, controlled trials, like a study run by the University of Oxford called Recovery, which looked at the efficacy of hydroxychloroquine, tocilizumab, convalescent plasma, dexamethasone and two other treatments. At some hospitals in Britain, as many as about 60 percent of patients were enrolled in Recovery trials; even the Northwell system, which is committed to research, was able to enroll, at its most trial-driven hospital, North Shore University Hospital, around only 20 percent of its patients in clinical trials. |
| A flood of patients all with the same illness presents logistical challenges to trials, but also the perfect conditions for them; that the American medical system could not harness more of those patients into randomized, controlled trials, said Peter Horby, one of the two chief investigators for Oxford’s Recovery trials, represents a lost opportunity. Whether or not convalescent plasma actually helps patients, for example, has not yet been resolved by a randomized, controlled trial despite the tens of thousands of doses that American patients have received, numbers that dwarf those in Britain. Given those numbers, American researchers “could have nailed it by now,” said Horby, whose own trial on convalescent plasma is still underway. | A flood of patients all with the same illness presents logistical challenges to trials, but also the perfect conditions for them; that the American medical system could not harness more of those patients into randomized, controlled trials, said Peter Horby, one of the two chief investigators for Oxford’s Recovery trials, represents a lost opportunity. Whether or not convalescent plasma actually helps patients, for example, has not yet been resolved by a randomized, controlled trial despite the tens of thousands of doses that American patients have received, numbers that dwarf those in Britain. Given those numbers, American researchers “could have nailed it by now,” said Horby, whose own trial on convalescent plasma is still underway. |
| Caplan, the N.Y.U. bioethicist, acknowledges that doctors in the United States did manage to enroll more patients in trials more quickly than ever. But even still, he believes that the commitment to long-shot efforts to rescue patients was stronger than the commitment to science, which slowed results and possibly cost more lives. “We did a lot,” he said. “But we could have gone faster and resolved questions sooner.” | Caplan, the N.Y.U. bioethicist, acknowledges that doctors in the United States did manage to enroll more patients in trials more quickly than ever. But even still, he believes that the commitment to long-shot efforts to rescue patients was stronger than the commitment to science, which slowed results and possibly cost more lives. “We did a lot,” he said. “But we could have gone faster and resolved questions sooner.” |
| If researchers see hydroxychloroquine’s failure as a cautionary tale about the perils of acting without evidence, Pierre Kory, the Wisconsin critical-care doctor, sees a different medical lesson emerging from the pandemic: that the emphasis on randomized, controlled trials can get in the way of doctors’ providing common-sense, lifesaving treatments. | If researchers see hydroxychloroquine’s failure as a cautionary tale about the perils of acting without evidence, Pierre Kory, the Wisconsin critical-care doctor, sees a different medical lesson emerging from the pandemic: that the emphasis on randomized, controlled trials can get in the way of doctors’ providing common-sense, lifesaving treatments. |
| In April, supportive care alone was considered the best option for patients with Covid-19, given that there was no evidence yet to back other treatments. Kory, who was then the chief of critical-care service at the University of Wisconsin Hospital and Clinics, believed instead that medications commonly used in critical care would most likely help critically ill Covid-19 patients, too. That month, at a well-attended meeting with fellows, residents and leadership, including Lynn Schnapp, the chair of the department of medicine at the University of Wisconsin medical school, Kory suggested an approach that went beyond supportive care. He had been consulting with senior hematologists at the hospital and had observed alarming blood clotting in Covid-19 patients. He and the hematologists proposed that the hospital consider administering an aggressive dose of anticoagulants to patients whose blood tests showed elevated risks for clotting. (Many medical-society guidelines that once called for only supportive care now recommend the use of anticoagulants in Covid-19 patients, but not in doses as aggressive as those that Kory and specialists at the hospital had proposed.) | In April, supportive care alone was considered the best option for patients with Covid-19, given that there was no evidence yet to back other treatments. Kory, who was then the chief of critical-care service at the University of Wisconsin Hospital and Clinics, believed instead that medications commonly used in critical care would most likely help critically ill Covid-19 patients, too. That month, at a well-attended meeting with fellows, residents and leadership, including Lynn Schnapp, the chair of the department of medicine at the University of Wisconsin medical school, Kory suggested an approach that went beyond supportive care. He had been consulting with senior hematologists at the hospital and had observed alarming blood clotting in Covid-19 patients. He and the hematologists proposed that the hospital consider administering an aggressive dose of anticoagulants to patients whose blood tests showed elevated risks for clotting. (Many medical-society guidelines that once called for only supportive care now recommend the use of anticoagulants in Covid-19 patients, but not in doses as aggressive as those that Kory and specialists at the hospital had proposed.) |
| The meeting among Kory and his colleagues took an adversarial turn. “No one else is doing this,” said Lynn Schnapp, as Kory recalls. (She denies saying that, although a former colleague of Kory’s who attended the meeting confirmed Kory’s account.) “There is no evidence,” a fellow I.C.U. doctor said more than once, her voice raised. Kory, who pointed out at the meeting that his suggestion was based on the opinion of the hospital’s own experts, says he fired back with equal intensity. “And this is Wisconsin,” he told me. “People don’t yell here.” Other colleagues who were supposed to jump off the call to attend another meeting later confided to Kory that they couldn’t bring themselves to leave, for fear of missing out on this unusual hospital drama. | The meeting among Kory and his colleagues took an adversarial turn. “No one else is doing this,” said Lynn Schnapp, as Kory recalls. (She denies saying that, although a former colleague of Kory’s who attended the meeting confirmed Kory’s account.) “There is no evidence,” a fellow I.C.U. doctor said more than once, her voice raised. Kory, who pointed out at the meeting that his suggestion was based on the opinion of the hospital’s own experts, says he fired back with equal intensity. “And this is Wisconsin,” he told me. “People don’t yell here.” Other colleagues who were supposed to jump off the call to attend another meeting later confided to Kory that they couldn’t bring themselves to leave, for fear of missing out on this unusual hospital drama. |
| At a subsequent, smaller meeting, Kory brought up with Nizar Jarjour, a division chief, the possibility of giving steroids, commonly used on critical-care patients, to Covid-19 patients in the I.C.U. “I don’t want to talk about it,” Jarjour said. | At a subsequent, smaller meeting, Kory brought up with Nizar Jarjour, a division chief, the possibility of giving steroids, commonly used on critical-care patients, to Covid-19 patients in the I.C.U. “I don’t want to talk about it,” Jarjour said. |
| In a lengthy email Jarjour later sent me, he explained that open discussion was welcome during that period of time; he also sympathized with the sentiments of the I.C.U. colleague who was urging caution while facing a novel virus. | In a lengthy email Jarjour later sent me, he explained that open discussion was welcome during that period of time; he also sympathized with the sentiments of the I.C.U. colleague who was urging caution while facing a novel virus. |
| Corticosteroids have a complicated and controversial history in critical-care medicine. Numerous trials over the past 50 years have been conducted on their efficacy in patients with acute respiratory distress syndrome, or ARDS, a diagnosis for patients who have reached a stage of perilous respiratory failure. Because many of those patients at that stage of illness have confounding factors, findings are far from definitive. But based largely on some meta-analyses, including those looking at how patients with MERS and SARS fared, the World Health Organization advised, early in the pandemic in this country, against the use of steroids in Covid-19 patients experiencing ARDS, which is to say, most patients on ventilators. | Corticosteroids have a complicated and controversial history in critical-care medicine. Numerous trials over the past 50 years have been conducted on their efficacy in patients with acute respiratory distress syndrome, or ARDS, a diagnosis for patients who have reached a stage of perilous respiratory failure. Because many of those patients at that stage of illness have confounding factors, findings are far from definitive. But based largely on some meta-analyses, including those looking at how patients with MERS and SARS fared, the World Health Organization advised, early in the pandemic in this country, against the use of steroids in Covid-19 patients experiencing ARDS, which is to say, most patients on ventilators. |
| Kory and several colleagues at hospitals around the country noted that the studies that the W.H.O. cited, for example, were largely not randomized and controlled; other relevant institutions like the Society of Critical Care Medicine, whose doctors treat the most ill patients, and the European Society of Intensive Care Medicine did recommend the use of steroids for ventilated Covid-19 patients with ARDS. Also, in Kory’s own clinical experience, corticosteroids could be lifesavers. He did not see them as a wild-card drug for this disease, like hydroxychloroquine; he used them for non-Covid-19 patients who were facing cytokine storms or ARDS. He was surprised by the heat with which colleagues challenged him when he made the recommendation, and he believed that his own leadership role in conference calls subsequently diminished. He and Jarjour, he said, had more disagreements in three days than they had in the previous five years. | Kory and several colleagues at hospitals around the country noted that the studies that the W.H.O. cited, for example, were largely not randomized and controlled; other relevant institutions like the Society of Critical Care Medicine, whose doctors treat the most ill patients, and the European Society of Intensive Care Medicine did recommend the use of steroids for ventilated Covid-19 patients with ARDS. Also, in Kory’s own clinical experience, corticosteroids could be lifesavers. He did not see them as a wild-card drug for this disease, like hydroxychloroquine; he used them for non-Covid-19 patients who were facing cytokine storms or ARDS. He was surprised by the heat with which colleagues challenged him when he made the recommendation, and he believed that his own leadership role in conference calls subsequently diminished. He and Jarjour, he said, had more disagreements in three days than they had in the previous five years. |
| On April 7, Kory’s colleague Ellie Golestanian sent an email to Kory and others, at 1:32 a.m., in response to another colleague’s call for the use of corticosteroids and anticoagulants: “In patients with severe Covid-19, we are fumbling in the dark, clutching at anything that might work. But as you are well aware, just because a therapy ‘should’ work, or we desperately ‘want’ it to work — it does not follow that it ‘will’ work.” | On April 7, Kory’s colleague Ellie Golestanian sent an email to Kory and others, at 1:32 a.m., in response to another colleague’s call for the use of corticosteroids and anticoagulants: “In patients with severe Covid-19, we are fumbling in the dark, clutching at anything that might work. But as you are well aware, just because a therapy ‘should’ work, or we desperately ‘want’ it to work — it does not follow that it ‘will’ work.” |
| “When I hear stuff like corticosteroids described as experimental and unproven, I want to jump out a window,” Kory told me later that month. “They make it sound like we are experimenting on people. I want to be respectful of my colleagues, but I feel like they are getting it 100 percent wrong. I’ve never seen smarter people get a problem more wrong. Because they are running hypotheses in a lab and so many of them fail, they think when I approach a patient, I am testing out a hypothesis. It’s not like a hypothesis, but more like a problem, and I have to figure out how to fix it with a couple of decades of experience to back me up. It’s a stretch to call it a hypothesis. It’s just me doctoring.” | “When I hear stuff like corticosteroids described as experimental and unproven, I want to jump out a window,” Kory told me later that month. “They make it sound like we are experimenting on people. I want to be respectful of my colleagues, but I feel like they are getting it 100 percent wrong. I’ve never seen smarter people get a problem more wrong. Because they are running hypotheses in a lab and so many of them fail, they think when I approach a patient, I am testing out a hypothesis. It’s not like a hypothesis, but more like a problem, and I have to figure out how to fix it with a couple of decades of experience to back me up. It’s a stretch to call it a hypothesis. It’s just me doctoring.” |
| Kory was so frustrated about the hospital’s approach that in May he resigned, taking a job instead at Aurora St. Luke’s Medical Center in Milwaukee. “Our differences were so far apart, I felt I couldn’t be a part of it,” said Kory, who foresaw, in April, a “catastrophe” if doctors at any hospital could apply only supportive care. A colleague of his in New York, an I.C.U. doctor affiliated with a major medical center, confirmed that he, too, resigned from his hospital, in part because of tensions around his decision to try an F.D.A.-approved medication off-label and outside a trial. In May, Kory, following his disagreement in Wisconsin, spent several weeks in New York treating patients, often with steroids. | Kory was so frustrated about the hospital’s approach that in May he resigned, taking a job instead at Aurora St. Luke’s Medical Center in Milwaukee. “Our differences were so far apart, I felt I couldn’t be a part of it,” said Kory, who foresaw, in April, a “catastrophe” if doctors at any hospital could apply only supportive care. A colleague of his in New York, an I.C.U. doctor affiliated with a major medical center, confirmed that he, too, resigned from his hospital, in part because of tensions around his decision to try an F.D.A.-approved medication off-label and outside a trial. In May, Kory, following his disagreement in Wisconsin, spent several weeks in New York treating patients, often with steroids. |
| In June, Oxford posted a preliminary report for its Recovery trial of more than 6,000 patients who received either standard care or dexamethasone, a steroid similar to the ones that Kory and other I.C.U. doctors had been advocating. At least when administered to patients who were already on oxygen or ventilators, the drug saved lives. | In June, Oxford posted a preliminary report for its Recovery trial of more than 6,000 patients who received either standard care or dexamethasone, a steroid similar to the ones that Kory and other I.C.U. doctors had been advocating. At least when administered to patients who were already on oxygen or ventilators, the drug saved lives. |
| Kory sees, in the Oxford results, a story of triumph. He believes that he successfully treated patients with steroids and that the Recovery trial results prove it. And yet if patients did not respond, he would go further, increasing the dose, in a few instances, to a level 10 times as strong as that in the trial. Did the higher dosage increase the risk? The answer to that question, a research purist like Kevin Tracey would point out, is still unknown. Despite the enthusiasm for the Recovery trial, Tracey maintains that even one stellar randomized, controlled trial does not settle the question of the use of steroids for patients with Covid-19. “It needs to be replicated,” he said. Given the long, complicated history of steroid studies, he predicts that sometime down the road another statistically powerful randomized, controlled trial will yield contradictory findings. In Tracey’s reservations, Kory sees not rational evaluation but bias. “That’s a 6,000-person trial he’s discrediting,” Kory said. “That’s a person who will never be convinced.” | Kory sees, in the Oxford results, a story of triumph. He believes that he successfully treated patients with steroids and that the Recovery trial results prove it. And yet if patients did not respond, he would go further, increasing the dose, in a few instances, to a level 10 times as strong as that in the trial. Did the higher dosage increase the risk? The answer to that question, a research purist like Kevin Tracey would point out, is still unknown. Despite the enthusiasm for the Recovery trial, Tracey maintains that even one stellar randomized, controlled trial does not settle the question of the use of steroids for patients with Covid-19. “It needs to be replicated,” he said. Given the long, complicated history of steroid studies, he predicts that sometime down the road another statistically powerful randomized, controlled trial will yield contradictory findings. In Tracey’s reservations, Kory sees not rational evaluation but bias. “That’s a 6,000-person trial he’s discrediting,” Kory said. “That’s a person who will never be convinced.” |
| Kory is also part of a group of critical-care doctors who widely disseminated a protocol for treating Covid-19 that includes anticoagulants and steroids but also other treatments — including Pepcid and intravenous vitamin C — whose efficacy is hotly contested among doctors. | Kory is also part of a group of critical-care doctors who widely disseminated a protocol for treating Covid-19 that includes anticoagulants and steroids but also other treatments — including Pepcid and intravenous vitamin C — whose efficacy is hotly contested among doctors. |
| Should Kory and his colleagues have been administering steroids when they did? Were they right? Kory thinks so. But Eric Rubin, the editor of The New England Journal of Medicine, thinks it’s not so clear-cut. “You could also say he was lucky,” Rubin said. | Should Kory and his colleagues have been administering steroids when they did? Were they right? Kory thinks so. But Eric Rubin, the editor of The New England Journal of Medicine, thinks it’s not so clear-cut. “You could also say he was lucky,” Rubin said. |
| At times, over the course of several conversations, Rubin defended the bond between doctors and patients, the need for physician autonomy, the necessity of making judgments in the absence of evidence, especially when mortality rates were so high; at other times he seemed frustrated that doctors were still relying on treatments for which there was no evidence, concerned that a lack of equipoise had possibly muddled the course of research. “I know I seem to be saying opposite things,” he admitted. “And I agree with myself.” | At times, over the course of several conversations, Rubin defended the bond between doctors and patients, the need for physician autonomy, the necessity of making judgments in the absence of evidence, especially when mortality rates were so high; at other times he seemed frustrated that doctors were still relying on treatments for which there was no evidence, concerned that a lack of equipoise had possibly muddled the course of research. “I know I seem to be saying opposite things,” he admitted. “And I agree with myself.” |
| Rubin is an infectious-disease doctor at Brigham and Women’s Hospital in Boston, and like many doctors in that specialty, he had strong reservations about steroids. He advised colleagues against using them. “And I was wrong,” he said. He also acknowledges that he was less opposed to the use of tocilizumab, although that, too, was untested and could also increase the risk of infection. I asked him whether perhaps there was something about tocilizumab’s novelty, even its scarcity, its high price, that may have given it a sheen of credibility? In the absence of evidence, we are all susceptible to predictable irrational biases. “We know less about toci,” is how Rubin said he thought about it at the time: It left open the possibility that it could be helpful, although of course that means it also left open the possibility that it could do more harm than supportive care, more harm even than steroids. Unlike steroids, tocilizumab was not yet the devil he knew. Rubin could see, months later, his decision-making process with humility. “I can’t argue that I was super rational either,” he finally said. | Rubin is an infectious-disease doctor at Brigham and Women’s Hospital in Boston, and like many doctors in that specialty, he had strong reservations about steroids. He advised colleagues against using them. “And I was wrong,” he said. He also acknowledges that he was less opposed to the use of tocilizumab, although that, too, was untested and could also increase the risk of infection. I asked him whether perhaps there was something about tocilizumab’s novelty, even its scarcity, its high price, that may have given it a sheen of credibility? In the absence of evidence, we are all susceptible to predictable irrational biases. “We know less about toci,” is how Rubin said he thought about it at the time: It left open the possibility that it could be helpful, although of course that means it also left open the possibility that it could do more harm than supportive care, more harm even than steroids. Unlike steroids, tocilizumab was not yet the devil he knew. Rubin could see, months later, his decision-making process with humility. “I can’t argue that I was super rational either,” he finally said. |
| At the peak of the surge, Rubin was far from the only doctor whose usual commitment to evidence faltered. “There would be a physician that would have said, ‘No, no, no,’ and all of the sudden, it’s his mother,” Aberg, the Mount Sinai doctor, told me. “All of a sudden, let me tell you, they wanted everything. We had some of our own physicians admitted, and people were just crazed about what they wanted to do to those individuals.” Kevin Tracey, the Feinstein researcher, says that overwhelming uncertainty was driving people’s reactions: “We just lived through a plague. It was life and death. Fear. Ignorance. You were seeing raw human behavior in survival mode, a classic reaction to threat.” | At the peak of the surge, Rubin was far from the only doctor whose usual commitment to evidence faltered. “There would be a physician that would have said, ‘No, no, no,’ and all of the sudden, it’s his mother,” Aberg, the Mount Sinai doctor, told me. “All of a sudden, let me tell you, they wanted everything. We had some of our own physicians admitted, and people were just crazed about what they wanted to do to those individuals.” Kevin Tracey, the Feinstein researcher, says that overwhelming uncertainty was driving people’s reactions: “We just lived through a plague. It was life and death. Fear. Ignorance. You were seeing raw human behavior in survival mode, a classic reaction to threat.” |
| In recent months, a relative calm has set in. Since that tense mid-May meeting between the researcher Spyropoulos and his colleagues on the ground at Long Island Jewish Medical Center, clinicians and researchers have forged more compromise through a series of conversations. Looking back at that time, one critical-care doctor mentioned that Spyropoulos, when he called in by videoconference that day, seemed tired and stressed; perhaps, the critical-care doctor thought, that accounted for why Spyropoulos had spoken so harshly to the group. | In recent months, a relative calm has set in. Since that tense mid-May meeting between the researcher Spyropoulos and his colleagues on the ground at Long Island Jewish Medical Center, clinicians and researchers have forged more compromise through a series of conversations. Looking back at that time, one critical-care doctor mentioned that Spyropoulos, when he called in by videoconference that day, seemed tired and stressed; perhaps, the critical-care doctor thought, that accounted for why Spyropoulos had spoken so harshly to the group. |
| Spyropoulos, the director of the anticoagulation program at Northwell, had in fact been working 19-hour days to try to get the trial up and running at breakneck speed. He also mentioned to me in passing, during an interview, that both he and his wife had been sick with Covid-19, his wife more so than him. Perhaps, like many doctors, he was laboring under the additional stress of having not just a professional but a deeply personal struggle with the power of the disease. In response to a text I sent asking about the extent of his wife’s illness, Spyropoulos wrote back on July 11. “My wife was very sick and bedridden for 3 days (I was mildly symptomatic) but she responded well to hydroxychloroquine,” he wrote. | Spyropoulos, the director of the anticoagulation program at Northwell, had in fact been working 19-hour days to try to get the trial up and running at breakneck speed. He also mentioned to me in passing, during an interview, that both he and his wife had been sick with Covid-19, his wife more so than him. Perhaps, like many doctors, he was laboring under the additional stress of having not just a professional but a deeply personal struggle with the power of the disease. In response to a text I sent asking about the extent of his wife’s illness, Spyropoulos wrote back on July 11. “My wife was very sick and bedridden for 3 days (I was mildly symptomatic) but she responded well to hydroxychloroquine,” he wrote. |
| His casual certainty about the cause and effect of her recovery was surprising. His wife had been ill, taken hydroxychloroquine and recovered. Whether the second event caused the third was at best unknown but statistically unlikely, given the now-significant body of research showing that the drug does not help. As if even Spyropoulos recognized that his comment was less than rational, he went on to rehearse the argument he made to his colleagues at Long Island Jewish about the importance of relying on research. Anything else, he repeated, was witchcraft. | His casual certainty about the cause and effect of her recovery was surprising. His wife had been ill, taken hydroxychloroquine and recovered. Whether the second event caused the third was at best unknown but statistically unlikely, given the now-significant body of research showing that the drug does not help. As if even Spyropoulos recognized that his comment was less than rational, he went on to rehearse the argument he made to his colleagues at Long Island Jewish about the importance of relying on research. Anything else, he repeated, was witchcraft. |