When British scientists studying potential treatments for COVID-19 released early results on hydroxychloroquine in June, it was not good news.
For patients sick enough with the coronavirus to be hospitalized, there was no evidence the controversial malaria drug did them any good. The RECOVERY trial found the same for the HIV therapy lopinavir .
The findings had a dramatic effect. Around the world ethics boards and funding bodies ended “dozens if not hundreds” of studies on hydroxychloroquine and lopanivir, says Edward Mills, a Canadian clinical trials expert.
The problem with that, he says, is that many of those other trials were looking at the medicines as a treatment for outpatients in a milder phase of the disease, or as a “prophylaxis” to prevent infection in the first place.
The impact on severely ill patients — what the widely respected U.K. trial examined — was largely irrelevant to their work, says Mills, a McMaster University professor who advises the Gates Foundation on clinical trials.
The episode was typical of what has become a serious problem in the COVID-19 pandemic: misinterpretation of trial data, with “disastrous” results for other studies, Mills and colleagues argue in a recent medical journal commentary .
Influenced by media accounts, scientific oversight boards often don’t recognize there are distinct phases to COVID-19 sickness, and that what works at one point in the disease may be useless at another — or vice versa, they wrote in Lancet Global Health.
“The scientific community has been no better versed on the complications of COVID than the general public ,” Mills said in an interview. “I’m tremendously disappointed in the scientific community and what I see is a lack of critical interpretation of this complex disease.”
Sir Nick White, an Oxford University tropical-medicine professor, confirmed by email that his own planned study of hydroxychloroquine as a preventive was ordered shut down because of the RECOVERY results.
White convinced U.K. authorities to reverse that decision, but said in his own journal paper this month that a number of such trials “are now under substantial threat, as some regulatory agencies have actively stopped ongoing studies.”
Prematurely ending trials because of misinterpretation and other factors means it’s still unknown whether drugs like hydroxychloroquine could, in fact, be useful as preventives or early in the illness, Mills said.
He traces the problem in part to the unprecedented way science is being communicated during the pandemic.
Instead of a sober exchange of peer-reviewed journal papers, research is often first published on “pre-print” websites or in news releases without review, then reported by journalists and spread through social media.
“Never before have we seen a medical scenario become such a public topic, where you have the president of the United States and the president of other countries weighing in on whether a drug works or not,” he noted. “And then you have the public weighing in on whether they agree with that individual, based on their own politics. This is unheard-of.”
Meanwhile, experts who rule on funding requests and ethics approvals can be unaware that there are at least five distinct phases of COVID-19, the Canadians’ paper said.
A drug with possible anti-viral capabilities, like hydroxychloroquine, may help a patient in the early stages of the disease when the virus itself is the threat. But it’s unlikely to help a patient who is severely ill and in the intensive-care unit, at which point the enemy is an exaggerated immune response and inflammation, said Mills.
Even the drug Remdesivir — a modest success story among COVID treatments — was found in one study to have little benefit when begun an average of 11 days after symptoms started. Another trial, however, concluded that it hastened recovery when administered two days earlier, noted the commentary.
The RECOVERY trial looked at only hospitalized patients, but had a much wider fallout, and not just on White’s study.
The Crown Coronation trial headed by Washington University in St. Louis was set to study hydroxychloroquine as a prophylaxis for 40,000 front-line health workers, but researchers were told to switch gears because of RECOVERY’s findings, said Mills.
An ethics board in South Africa halted a trial on using lopinavir on COVID outpatients because of RECOVERY’s hospital patient results. Investigators eventually persuaded the board to change its ruling, but lost eight crucial weeks amid the debate, said Miils.
That and other problems leave him worried that the current pandemic will end without a good handle on how to effectively treat those people who still get sick — and before they end up in hospital.
