Wartime doctors battling covid-19 rush to treat the ill — but without knowing what really works

Wartime doctors battling covid-19 rush to treat the ill — but without knowing what really works
By Carolyn Y. Johnson
Aug 16 2020
https://www.washingtonpost.com/health/2020/08/16/wartime-doctors-battling-covid-19-rush-treat-ill-without-knowing-what-really-works/

For most of April, Marylu Seidel felt like she was starring in a science fiction movie. Her husband of 34 years, Jeff, was sedated in an intensive care unit more than an hour’s drive away in Madison, Wis., and her only window into his world was a daily phone call with his nurses. His doctors, first at a local community hospital and then at the University of Wisconsin Hospital and Clinics, tried everything to help Jeff defeat the novel coronavirus — a ventilator, an antibiotic, an antimalarial drug, blood thinners, a blood plasma transfusion.

Today, Jeff is alive, one of millions of people who have recovered after being diagnosed with covid-19, the illness caused by the coronavirus. But if you ask his grateful family or even his doctors what kept him alive, the answer is unsettling.

“We don’t know, and they don’t really know either,” Marylu said.

Seven months into the pandemic, front-line doctors have in many cases become experts in treating covid-19. But they are experts without, for the most part, the most fundamental tool in medicine — solid evidence upon which to base their decisions.

When the coronavirus appeared in the United States in late January, hopes were high for quick progress: Science would find a treatment for people with the illness and develop a vaccine to prevent future cases.

Today, the vaccine race is on, but answers about treatments remain frustratingly elusive, with a handful of basic therapies supported by evidence, and a messy and imperfect scramble to extract information about what works from what has been given to thousands of patients. Therapeutic regimens vary from hospital to hospital, and much of what is offered is supported by hints and hunches — what official treatment guidelines refer to as a “knowledge gap.”

“There’s a lot of things about this pandemic that have been so challenging, and I just don’t think in the early days people really appreciated how important it was to set up rigorous clinical studies right away of treatments,” said Kevin Schulman, a professor of medicine at Stanford University School of Medicine. “We’re so focused on a vaccine, and hopefully they work. We’re a little less focused on drug trials and other treatments.”

Among other therapies, Jeff Seidel was given the anti-malarial drug hydroxychloroquine. It has since fallen out of vogue, in large part because of a big clinical trial in the United Kingdom that tested multiple drugs against placebos and found it did not work.

The National Institutes of Health is preparing to launch a large, randomized trial to formally test different doses of blood thinners, which have been widely used to treat blood clots caused by the virus. Blood plasma from people who have recovered has now been given to more than 60,000 covid-19 patients, but the evidence that it works is still only suggestive.

“It is unfortunate we don’t have the kinds of data we would like to have now,” said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. “That emphasizes and underscores something I repetitively talk about: the importance of the placebo-controlled randomized trial. Because if that had been done, we would have the answer to that right now … we could have [had] that answer some time ago.”

Medicine in a war zone

Rock-solid medical evidence depends on clinical trials, human experiments in which patients receive the real drug or a placebo. A flip of the coin determines whether patients get the real thing, and neither they nor their doctor know who is on the drug. These human experiments are essential, because even drugs backed by the most sensible rationale and promising lab research are often foiled by the trickiness of human biology.

But the uneven use of evidence to inform medical practice has long been a fissure running down the middle of American medicine — and that has turned into a chasm during the urgency of the pandemic.

“The U.S., for better and worse, is an every-person-for-himself kind of place,” said Christopher P. Austin, director of the National Center for Advancing Translational Sciences, part of the National Institutes of Health, the nation’s biomedical research agency. “ ‘Don’t tell me what to do, I’ve got the greatest idea in the world.’ Scientific discovery relies on that. But it is, in a situation like this, it is a counter-current.”

In normal times, doctors debate the art and science of medicine, argue for and against rigid guidelines and constantly navigate the gaps between peer-reviewed findings and their own years of experience. In a pandemic, when overwhelmed doctors scramble to treat patients, exhaust intensive care unit beds and are forced to reuse basic protective equipment, organizing the complex trials needed to rigorously test treatments has been even harder.

“It’s really a reflection of our general approach to clinical research,” said Robert Califf, a former commissioner of the Food and Drug Administration. “The pandemic has really exposed all the weaknesses that we already knew were there.”

Jeanne Marrazzo, an infectious diseases specialist at the University of Alabama at Birmingham, oversaw testing of remdesivir, an antiviral drug tested in a randomized trial that has since been authorized and is one of the research success stories of the pandemic. She says hand-wringing about the lack of gold-standard evidence simply does not take into account the situation on the ground.

“I think of what my clinical research team went through to enroll people in that trial, and I thought my nurses were going to die. One of them got covid and got sick,” Marrazzo said. In those early days, it took so long to get coronavirus test results that it could take a full day to get a patient qualified and screened for the study.

“Imagine trying to do that on a daily basis, multiple patients, some of them facing intubation, none of them have their families” with them, Marrazzo said.

On top of that, President Trump, the media and even doctors have often pushed the idea that unproven treatments are extremely promising, making it harder to ask families to take a placebo.

Judith Aberg, chief of the division of infectious diseases at Mount Sinai Health System in New York who runs clinical trials, said she finds herself spanning an uneasy divide. Her health system set up randomized trials for some treatments, but not for others. That may have been a lost opportunity to gather precious data in the United States, but the chaos of delivering care in a pandemic made some medical ideals impossible.

“It’s not good science. But you’re talking about how many people died. There was one day our system had 84 deaths,” Aberg said. “And then you’re going to ask me to potentially put them on a placebo? It’s just really heart wrenching, talking with families, if your patients are able to communicate — and you’re dealing with all these deaths.”

But physicians’ decisions on how to use unproved treatments on dying patients reverberate: Doctors may never know why that individual patient recovered or got worse — but they also do not gain crucial knowledge about how to treat the next hundred, or thousand, patients.

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