Recent news reports have questioned the use of hydroxychloroquine for treating COVID-19. Research at Intermountain Healthcare remains focused on finding answers while ensuring safety and access for patients. Here’s a look at the context of these news reports, the types of medical research that are being conducted, and how clinical trials ensure safety.
What different types of medical research exist?
Medical decisions are based on a concept called “level of evidence” – or the quality of scientific research supporting the use of a treatment. Randomized controlled trials (RCTs) produce the highest level of evidence. They’re considered the standard for determining whether a treatment works or not. The Food and Drug Administration requires at least two randomized controlled trials before a drug is approved. Other types of research studies can also advance medical knowledge. This research is important and useful but does have some limitations. One limitation is the difficulty in confirming whether an observation was caused by a particular treatment being tested or influenced by other factors.
What do the results of the recent Lancet study mean for the future of hydroxychloroquine?
A study was published last week in the medical journal Lancet that aimed to evaluate the effect of hydroxychloroquine and chloroquine, with or without azithromycin in hospitalized patients with COVID-19. This wasn’t a randomized controlled trial, but rather a study using data uploaded to an international surgical outcomes registry. This study suggested that use of hydroxychloroquine or chloroquine was associated with lower rates of survival and higher rates of arrhythmias.
The study had significant limitations. First, the study didn’t have a control group. It’s likely that patients who weren’t treated with hydroxychloroquine weren’t as severely ill as those who were. Of the 96,000 patients in the registry, only about 10,000 received hydroxychloroquine and chloroquine with or without azithromycin, and those patients were compared with people who didn’t receive any medications. Even with statistical methods, it’s difficult to compare patients and describe why one might be sicker than another. This gives the appearance that the medications not only didn’t work but also are associated with worse outcomes. The authors of the Lancet article acknowledge this, and state “randomized clinical trials will be required before any conclusion can be reached regarding benefit or harm of these agents in COVID-19.”
The WHO recently suspended their hydroxychloroquine trial. Does that prove this drug isn’t safe?
No, it doesn’t. There are multiple randomized controlled trials underway to study whether hydroxychloroquine has a benefit in the treatment of COVID-19. Each of these trials has an independent panel of experts who are unblinded to the study data and are responsible for ensuring the trial is conducted according to rigorous standards and is safe. One of these trials, the SOLIDARITY trial, is being conducted by the World Health Organization (WHO), which announced they’d decided to temporarily stop enrolling new patients but will continue trial for currently enrolled patients, to allow their safety monitoring panel to check for safety in the study.
Pausing studies is a common practice. Safety monitoring panels periodically check for safety throughout a trial and may pause a study to investigate certain findings. SOLIDARITY trial investigators also stated this weekend that no safety concerns were found in previous checks, but they were proceeding with an abundance of caution. This is in fact one of the strengths of clinical trials — to carefully and safely answer important questions. The safety panel for the largest COVID-19 trial in the world, the RECOVERY UK trial, also recently conducted a review of their unblinded data for the hydroxychloroquine and concluded it was safe to continue enrollment in their trial.
What does this mean for local hydroxychloroquine trials?
Like other high-quality randomized controlled trials, the hydroxychloroquine trials in Utah are being carefully conducted in a way that puts patient safety first, while determining whether the drug is effective and providing access to potentially valuable medications in a monitored way.
The HAHPS study, the HyAzOUT study, and the UtahCOVIDTrial each have independent safety monitoring panels staffed by clinical trial experts from other academic centers experienced in running trials. These panels are periodically reviewing results that the study investigators aren’t allowed to see and have the power to stop the trials if they identify safety concerns. This adds additional safety to the careful patient selection and monitoring already in place.
The investigators of the Utah hydroxychloroquine studies remain committed to protecting the safety of participants, and to helping produce high-quality evidence that will lead the way in establishing the best way to treat COVID-19.