Bioethicist Pilar Ossorio says the world could be at risk of sacrificing essential knowledge for fighting COVID-19 and future deadly viruses if the COVID-19 response is not accompanied by sound research.
The proof? Look to the Ebola crisis.
Ossorio, the bioethicist in residence at the Morgridge Institute for Research and professor of law at the University of Wisconsin-Madison, has been in the middle of a virtual hurricane of ethical discourse around COVID-19, on everything from ventilator allocation to drug repurposing and clinical trials in a time of pandemic. One challenging ethical development is the high-level advocacy for trying drugs that “might help” COVID patients without any sound clinical evidence to justify their use.
It’s a problematic path for many reasons, Ossorio says. First, even if the drug has been approved for other uses, it may have adverse effects on a population it wasn’t intended for. Second, it can lead to shortages in availability of the drug for its original patients. And third, in the absence of well-designed clinical trials, clinicians will never be able to discern the actual impact the drug had on a patient.
The third point is actually one of the hard lessons to come from the 2014-2015 Ebola crisis, Ossorio says. There were eight separate drug or vaccine-related therapies attempted during the outbreak, and collectively they produced very little direction toward a breakthrough. An in-depth report by the journal Science called “Thin Harvest” documented that many of the clinical trials had fundamental flaws or a lack of follow-through that would have informed future studies.
“We learned in the Ebola outbreaks that if you do panicked, sloppy research, at the end of it you won’t know anything,” Ossorio says. “You can’t help people in the next Ebola outbreak any better than you helped them in this outbreak, because you didn’t do good research.”
We may miss opportunities again, Ossorio says. For example, scientists have recognized that the extreme respiratory problems triggered by COVID-19 closely resemble those of a “cytokine storm,” a runaway immune response that can occur in some immunotherapy patients or patients with influenza. There are drugs that can help block this extreme response in patients who are getting T cell therapies to fight cancer. It has tremendous potential as a crossover therapy for COVID-19, but there is deep division in medicine about the ethics of using research techniques such as randomization and controls in clinical trials during a pandemic.
“But fast-tracking does not mean that we can skip the fundamentals of research design or analysis.”Pilar Ossorio
Given the scope of COVID-19, Ossorio says she worries that the natural and understandable desire to move as fast as possible to combat the pandemic may lead to shortcuts that don’t produce the tools to make a lasting impact.
“One of the things about this pandemic is there’s reason to think that this is going to go on for a while,” she says. “That we’ll have social distancing, we’ll flatten the curve and we’ll let people out of their houses to go back to work, and then there will be another uptick. And then we’re going to have to go back into house arrest for a while.
“Flattening the curve means this is going to be simmering along and kind of coming in waves for a while,” she adds. “If we can do good clinical trials now, that can actually have an impact a year from now or six months from now. And we’ll be so much better off if we buckle down now, as early as we can, and do randomized and controlled trials.”
Some research responses have been promising, she adds. In order to accelerate vaccine developments, scientists around the world created platforms to quickly share data. That effort along with the massive scope of investment, ramp-up of science and logistical support may help shave months off the vaccine process. And fast-tracking some existing drugs also makes sense when there is a “plausible biological mechanism” for why it might be effective, she says.
“But fast-tracking does not mean that we can skip the fundamentals of research design or analysis,” Ossorio says. “Numerous low-quality trials done in a pandemic might only leave us with more uncertainty about effective and appropriate treatments.”
Even without the current pandemic, Ossorio says the past decade has seen an aggressive movement for the Food and Drug Administration (FDA) to make experimental and unproven drugs available more quickly, even though the vast majority of drug candidates that look initially promising fail to demonstrate their safety and effectiveness. Scientists and companies spend billions annually on drug clinical trials, but only about one in ten drugs reach the marketplace.
“The truth is you still have to design good trials,” Ossorio says. “And the fact that we’re in an emergency doesn’t change that.”