In early April, President Trump, in his daily press briefing, told Americans to take the drug hydroxychloroquine, calling it a “game changer” for people with COVID-19:
“I really think they should take it. But it’s their choice. And it’s their doctor’s choice or the doctors in the hospital. But hydroxychloroquine. Try it, if you’d like.”
This was not the first time he had touted this yet unproven treatment for COVID-19. But Trump’s pronouncements have mostly been balanced by Dr. Anthony Fauci’s much more cautious – and science-informed – explanations that there’s no scientific proof that the drug is effective to treat coronavirus infections, only some “anecdotal evidence”.
This global pandemic is upending our lives in unprecedented ways, taxing our health system beyond capacity and killing thousands. So it is hard for many Americans, who are desperate for a cure, to hear the more measured approach of the scientists urging caution, patience and restraint.
Surely, it would be great to have a drug that could treat COVID-19, cure or even prevent it. But the reality is that hydroxychloroquine is not ready for prime time as a response to COVID-19. Not yet. Thinking that it is, prematurely, could be its own kind of disaster.
Here is what we know about hydroxychloroquine
Also known by its brand name, Plaquenil, this drug has long been approved to prevent or treat malaria. It is also used to treat certain autoimmune conditions like lupus and rheumatoid arthritis.
The idea that it has a role to play in the current crisis is not without a theoretical basis. The drug could make it harder for the SARS-CoV2 virus to enter the cells and replicate there. It also might help quell autoimmune reactions. This could reduce the sometimes massive and dangerous anti-inflammatory reaction that occurs in infected people.
At the moment, these theories have scant evidence to support them. There are fewer than a handful of studies looking directly at what happens when hydroxychloroquine meets COVID-19. None of them establishes what people want to hear — that this drug is the cure.
There are five reasons that the studies to date are not enough
- First, some of the early studies were carried out were in vitro. This means they were done in the lab, on cells, and not in living, breathing humans. Unfortunately, the leap from petri dish to human is huge. What happens in one rarely translates to what happens in the other.
- Second, the few studies where the drug was administered to humans have each involved a tiny number of people. The smaller the study population, the harder it is to draw conclusions and apply the results to larger, more diverse populations. The research archives are full of stories of promising small studies that disappointed expectations in this way.
- Third, there have been problems with the methods used in all of the studies. Researchers take steps to increase the chances that their results are real. These protocols are designed to reduce investigator bias (something all of us have) and reduce factors like chance. In the rush to provide data, the studies reported so far fall short of these standards.
- Fourth, there has been no uniformity in what endpoints scientists investigated. Some studies measured the drug’s effect on the patients’ coughing and fever; others looked at how it affected the virus itself. All are worthwhile study targets, but they don’t tell us about the patients’ clinical status overall.
- Fifth, each study has used different dosages of hydroxychloroquine and suggested a different frequency of use.
It’s easy to misinterpret promising research findings
Exciting newspaper headlines can easily give the misguided impression that patients in studies, such as those conducted in France and China, are taking a pill and rising from their beds returned to full health. The details of the studies are far more mundane.
For example, among the 20 patients in the French study, those who took hydroxychloroquine had less virus in their system than those who took a common antibiotic. Among 62 hospitalized patients in the Chinese study, the half that received the drug had coughs that lasted for 2 days on average instead of 3. They also had fevers that lasted 2.2 days on average versus 3.2 days. And 25 of 31 people showed improvements in their pneumonia compared to 17 of 31 in the group that did not get the drug. No one in either study was cured by hydroxychloroquine.
This research is promising, but there are critical questions we need answered before the U.S. and the world considers treating COVID-19 patients with this drug. We need to know not only if we should give the drug to a patient, but when, how much and how often. In other words, at what stage of illness should we give the drug? What’s the right dose? And how many times a day?
That’s why hydroxychloroquine is not ready for prime time.
Why not try this drug as a Hail Mary pass for the very sick?
It’s a common question. With so many people severely sick, why not go for the Hail Mary pass? What’s the harm in letting people take the drug just in case?
In fact, there’s a lot to lose, even your life. All drugs have potential side effects, and this one is no different. The list of ways that hydroxychloroquine can hurt you is very long and can involve every body system and organ. Importantly, it can cause a severe depletion of blood particles. This means people may end up with too few white blood cells to fight infection or too few platelets that help the blood clot.
One of the drug’s most notorious and serious side effects is called prolonged-QT syndrome. This is a condition affecting the heart rate, which may trigger fainting, seizures or even death. It is the side effect that probably killed an Arizona man and sickened his wife, and sent multiple people in Nigeria to the hospital. Additionally, reports from around the world have begun to document increased incidents of drug toxicities.
Hasty and inappropriate pronouncements such as the ones President Trump made can also affect those who don’t have the disease. Healthy people have started calling their doctors and pharmacies asking for prescriptions and have started hoarding the medication. Some doctors and pharmacists even began stockpiling it themselves. This has caused shortages, driven prices up, and made it more difficult to fill prescriptions for those who need it.
Of course, this has a direct impact on those who currently rely on hydroxychloroquine to treat the conditions for which it has FDA approval, like lupus and rheumatoid arthritis. When they can’t get the drug because of a run on it, this harms them directly.
So, is hydroxychloroquine the answer, or part of it?
Maybe. The answer depends on getting results from some large randomized controlled trials, the gold standard for medical evidence. Those studies should help answer a series of questions: Are people receiving it dying less than those who are not? Are people on the drug showing a reduced need for intubation compared to those who are not on it? Are people getting it recovering faster altogether compared to those not getting it?
Some larger studies are already underway in the U.S. and globally. Meanwhile, the FDA has taken the highly unusual step of issuing an emergency authorization to use hydroxychloroquine experimentally for patients who are in the hospital. What’s needed now is time and patience. These studies and continuing clinical experience will help shed much-needed light on whether the hopes and claims are borne out.
In other words, we have to wait. It is not easy, but it is the prudent thing to do, as well as the moral thing. Until then hydroxychloroquine is not ready for prime time.
Ranit Mishori