When the federal government started handing out a newly authorized Covid-19 treatment last week, some hospitals weren’t sure they should accept their share. On the surface, it sounded crazy. Decline a medication that might keep patients from getting severely ill? But like so many other pandemic-time medical decisions, this one offered only flawed choices.
The medication is bamlanivimab, Eli Lilly’s monoclonal antibody, and it’s meant for keeping high-risk patients out of the hospital. But its use comes with a Venn diagram of difficulties. Hospitals need to find space and staff to administer it at a time when there’s hardly enough of either to treat those who are gravely sick, build a system to identify eligible patients, and figure out an ethical way to ration it — all without knowing exactly how well the treatment works.
The evidence is sparse enough that on Wednesday, the Infectious Diseases Society of America recommended against the treatment’s routine use — though it acknowledged that the drug was a reasonable option for someone at increased risk of severe Covid-19 who didn’t mind the uncertainty.
To those able to give the antibody, the equivocal results offered a thin veil of comfort over the uneasy reality of not having enough for everyone, and having to choose between them. “The data are so preliminary, we can’t say this is truly a lifesaving drug,” said Patrick Kinn, a clinical pharmacy specialist at the University of Iowa Hospitals and Clinics, where teams are trying to expand ICU bed capacity. “To a certain extent, that alleviates some of the difficulty in making decisions like that: We don’t feel like we’re withholding a proven, lifesaving drug.”
The stuff is made of lab-brewed proteins, designed to imitate those that our bodies produce to inactivate the new coronavirus. Adding synthetic antibodies early enough in the course of an infection could help give our own immune system a leg up — which is why President Trump got Regeneron’s experimental cocktail of two antibodies when he was sick, thrusting this sort of the therapy into the public eye.
But the Food and Drug Administration gave emergency authorization to Lilly’s one-antibody version on the same day that Pfizer’s first hopeful glimpse of vaccine efficacy data came out. As more results have emerged, the immunizations have sucked up most of the attention, which makes sense: The news signals a possible beginning of the end of the pandemic. “The vaccine is coming, but it’s going to take six months, nine months, before we have enough,” said Allison Suttle, chief medical officer of Sanford Health, which includes 46 hospitals in the midwest.
Hospitals are overwhelmed now — and that’s something that vaccines can’t immediately help with, and bamlanivimab potentially can. The results that unlocked the emergency use authorization showed that, among 465 patients with mild or moderate Covid-19, 10% of those who got a placebo wound up in the hospital or the ER, while only 3% of those who got the antibody did. “This would help us a lot in terms of our staffing,” Suttle said. “That’s huge for us.”
The questions lie in the details. Doctors can prescribe the drug for anyone who is coronavirus-positive, with mild to moderate symptoms, but who is at high risk of getting really sick. “We have for nine months been telling people, ‘If you have Covid and have mild to moderate symptoms, please stay home and isolate,” said Rochelle Walensky, chief of infectious diseases at Massachusetts General Hospital.
Now, a subset of those people are supposed to come in for an antibody infusion. That isn’t simple. It means having trained staff observe recipients for an hourlong medication drip, and then for another hour to make sure there aren’t side effects. But it can’t necessarily be in regular outpatient infusion centers, where cancer patients, for instance, come for chemotherapy: You don’t want highly infectious people mixing with almost anyone, let alone those who are most vulnerable.
So, as the federal government has started parceling the antibody out to state health departments, and they’ve in turn started divvying it up among hospitals, some of them are wondering if this is something they can take on. “They might not decline it outright. They might say, ‘Give our supply to x, or give our supply to y,’” said Ogechika Alozie, an infectious disease specialist and co-chair of the El Paso Covid-19 Task Force.
“We have had inquiries from hospitals asking if we could support their patient populations at our infusion sites,” said Mark Sullivan, executive director of pharmacy operations at Vanderbilt University Medical Center, in Nashville. “We’re kind of in a situation where we have to care for our own,” he added, but he expects that his team will soon be able to help other, smaller hospitals, though it will take some figuring out.
Even for bigger hospitals, administering this drug can involve reshuffling, with some setting up infusion centers in what used to be nursing homes, others cordoning off a part of their Covid-19 testing site or using a dialysis clinic, and yet others considering the local convention center.
Identifying who’s eligible is a challenge, too. There are many ways of officially being “at high risk.” You can have diabetes or chronic kidney disease. You can be obese or immune-suppressed or over 65. You can be a teenager with sickle cell disease. You can be someone 55 or older with hypertension. It’s a long list that encompasses a broad swath of the American population. But testing sites don’t always collect data on all the official risk factors. Some hospitals are using electronic medical records to automatically identify possible candidates; others are relying on doctor referrals.
There’s also an issue of timing. While the drug is supposed to be given as soon as possible after a positive coronavirus test and within 10 days of getting symptoms, the clinical trial on which it’s based involved people treated within 72 hours of a positive test. Many clinicians are using that as their rule of thumb, which doesn’t leave much time.
Then, there’s the issue of supply. There are vastly more eligible patients than there are available vials. “Which is even the scarcer resource, the drug or the infusion slot? They’re both extraordinarily scarce,” said Walensky, of Mass. General.
Specialists wish they had more data so they knew which patients were likeliest to benefit the most from treatment. “You have a very limited amount of drug, you don’t know a) if it works, and if it does, b) who in,” said Jason Pogue, an infectious disease pharmacist at the University of Michigan.
Many hospitals are using more stringent eligibility criteria than federal or state health authorities, prioritizing only patients who have a number of risk factors. Others are identifying patients based on logistics. At Houston Methodist, for instance, a lot of recruitment for clinical trials of such antibody treatments took place in the emergency department and the employee health clinic, explained Katherine Perez, an infectious disease pharmacist there, and so they’ll be using the same tack to spread the word about this drug.
“We’re going to target our emergency department and our employee health first, because those patients will at least, at a minimum, be coming in with symptoms that look and smell like Covid,” Perez said. “We’ll be able to do a test, our turnaround time is fairly quick.”
One of the greatest concerns remains equity, though. Every logistical hurdle is a possible barrier. If you live in an area where the hospital isn’t able to set up an infusion center, that might make it harder for you to get treatment. If you don’t have a doctor who’s able to refer you, that might get in the way, too.
At the University of Pittsburgh Medical Center, clinicians have tried to rectify that a little, by using a lottery in which every high-risk Covid-19 patient is eligible for the drug — but you’re more likely to be selected if you’re an essential worker or if you live in a city’s most disadvantaged census tracts, and a little less likely if you’re expected to die of an end-stage condition within the next year. The method is a way of using the medical tools available to lessen the inequalities of American health care rather than widening them.
“If we don’t take any measures to counteract this, the ledgers of who has died will be disproportionately filled with the disadvantaged,” said Douglas White, a UPMC ethicist and the vice chair of critical care medicine.
He hopes this algorithm will help fix that. But that can’t fix the dearth of data. For that, people will need to keep enrolling in ongoing clinical trials — though such conversations may not always be easy. As Walensky put it, “If we say, ‘You can enroll in a trial where you could be randomized to maybe get the drug,’ or ‘You could get the drug,’ what do you think people are going to decide?”