Clinical trials are ramping up in North Texas as hospitals begin to offer many of the experimental treatments that have received widespread attention in the news.

Baylor Scott & White Health’s research arm launched a trial of the experimental drug remdesivir just one day ahead of enrolling its first patient earlier this month. The hospital system also hopes to soon offer COVID-19 patients another experimental therapy — convalescent plasma — which takes antibodies from the blood of those who have recovered from COVID-19 and infuses them into patients who are ill.

UT Southwestern Medical Center has launched two remdesivir clinical trials and one that tests to see if the compound sarilumab can reduce inflammation in the lungs.

“This is a situation where we’re trying to develop a therapy for our community because all of us, even as health care providers or health care researchers, may be patients at one point in time,” said Dr. Robert Gottlieb, a cardiologist and principal investigator of Baylor’s active COVID-19 treatment trials. “It really creates this sense of urgency, yet at the same time you can’t be rushed or lose objectivity.”

Dr. Robert L. Gottlieb is principal investigator of Baylor Scott and White active clinical trials for COVID-19. He stood outside the research facility in Dallas on Thursday, March 26, 2020. (Tom Fox / Staff Photographer)

Even as excitement builds around promising treatments, scientists caution that sorting effective treatments from ineffective ones during a pandemic is challenging. The scientific process normally moves deliberatively, in stages that allow researchers to describe a problem first and then work to address it. Now, experts are doing both at once.

”This is not just fixing a plane while it’s flying — it’s fixing a plane that’s flying while its blueprints are still being drawn,” wrote the editor-in-chief of the journal Science in a recent editorial.

Misinformation during an emergency can slow the progress of trials. Over the last two weeks, President Donald Trump has praised the malaria drugs chloroquine and hydroxychloroquine several times during briefings, saying he was a “big fan” and had a good feeling about their ability to treat patients with COVID-19.

That type of boosterism, say experts, can dissuade patients from joining clinical trials where they might be randomly assigned to a control group that does not receive that therapy.

“It is imperative that officials be honest with the public and express the true uncertainty that surrounds these interventions,” said Alex John London, director of the Center for Ethics and Policy at Carnegie Mellon University. “That helps people to see clinical trials for what they are — the best method of discovering whether a new intervention works.”

Remdesivir was originally developed for the Ebola virus by the pharmaceutical company Gilead and tested for safety in human volunteers. More recently, studies have shown it could block the ability of SARS-CoV-2, the virus that causes COVID-19, to replicate in the lab.

The drug was also given to the first U.S. COVID-19 patient just as he began to need supplemental oxygen, and he later recovered, according to a case study published in The New England Journal of Medicine. Trump said of remdesivir and other drugs that they “could have a very positive effect, or a positive effect, maybe not very, but maybe positive,” and added that they were “very, very exciting."

Yet the evidence around remdesivir is inconclusive. “All new drugs are born guilty until proven innocent,” said Jonathan Kimmelman, a bioethicist at Montreal’s McGill University. “They're born under the presumption that they're unsafe and ineffective until you prove otherwise.”

Randomized, double-blind placebo-controlled clinical trials are the best way of identifying the safest and most effective treatments for any disease, he said.

Most trials divide patients into groups: Some receive the new drug at different dosages and others receive either the standard of care — the best care available that does not include the experimental treatment — or standard of care plus a placebo, an IV infusion or a pill that looks and tastes very much like the experimental treatment. Researchers then compare data from all the groups to determine which had the best outcomes.

“Randomized” means that patients are assigned to study groups at random, or by chance alone. “Double-blind” means that neither doctors nor patients know which group they were placed into and neither do the researchers who initially evaluate the results.

Dr. Mamta Jain, a professor of internal medicine at UT Southwestern Medical Center in Dallas (Brian Coats / UT Southwestern Medical Center)

“I recognize that sometimes it may feel uncomfortable to sign up for a trial in which you may be assigned to a placebo,” said Dr. Mamta Jain, a physician at UT Southwestern who is running the hospital’s clinical trials for COVID-19 treatments. “It’s important for us to very rigorously look at drug A and B and C and compare it to what we currently have — which is basically nothing — and see if it really works.” She added that trial volunteers are heroes because “they really help us to find better treatments for everyone.”

During pandemics, trials should be designed to be flexible in case they need to be expanded to include more novel therapies, or in case the standard of care evolves, said Martha Nason, a mathematical statistician at the National Institute of Allergy and Infectious Diseases, who works on clinical trial design and analysis.

In the remdesivir trial for moderately ill patients at Baylor, Gilead Sciences, the trial’s sponsor, has allowed patients assigned to the control group to receive standard of care plus the malaria drug hydroxychloroquine, if their physician feels it is in their best interest and prescribes it.

There is only anecdotal evidence that hydroxychloroquine can work against COVID-19, but many patients have asked for it anyway. Chris Ridley, a spokesperson for Gilead, said the company wanted to allow for the range of local treatment practices across countries and for changes in those practices as the understanding of COVID-19 evolves.

Doctors say they are working at top speed to sort through promising drug candidates and bring investigational trials to patients. It took Baylor Scott & White Research Institute, the hospital system’s research and development arm, just one week to implement the remdesivir trial from the day hospital officials contacted Gilead to inquire about it — a process that normally takes six months, said Baylor’s Gottlieb.

In recent days, Dallas has hit an inflection point in the scale of COVID-19 infections, he said. Cases of the flu have dropped off earlier than normal, perhaps due to social distancing, he said. Now, as he sees more and more patients with fever and cough, he assumes it’s something else, including COVID-19.

“This really does behave differently than influenza,” he said. “With influenza, you can usually point to a specific day when you got sick whereas, this coronavirus, lots of patients have mild to moderate symptoms that may be lingering for about a week and then they start getting much sicker.”

What keeps him going are the patients who are recovering and those that have already been discharged, including those who received experimental treatments from his trials. “When you have a patient that comes to us in need and they’re able to go home feeling better, that’s what this is all about,” he said.