When it was learned in March that hydroxychloroquine, an antimalarial drug, may be favorable in the COVID-19 remedy, more than 50 clinical trials were temporarily implemented.
Usually, clinical trials involve thousands of patients and dozens of scientists working under the direction of a large research consortium, a drug company or the federal government.
But many of the hydroxychloroquine trials resembled lone-wolf research, overseen by individual hospitals and universities, at times without the typical rigorous research standards.
As a result, a Milwaukee Journal Sentinel analysis found, the trials became a frenzied hodge-podge of undertakings — an unprecedented scientific free-for-all in which research overlapped, studies were poorly designed, and patients were given drugs of unproven benefit.
Perhaps most importantly, hydroxychloroquine and other powerful drugs may have exposed patients to potential serious side effects beyond the harm of COVID-19.
These side effects — or “adverse events,” as they are often called in medicine — will likely become an increasingly crucial issue in the coming months as scientists race for COVID-19 treatments and vaccines.
But because of long-standing weaknesses in the U.S. Food and Drug Administration formula. To monitor these side effects, the figure may never be fully revealed.
The system has suffered from large-scale under-reporting of adverse events for decades. And because reporting is mandatory only for drug companies — not the hospitals that may have been operating the trials — those adverse events don’t have to be reported.
“Since we can send a spaceship to Pluto, we would have a greater formula for adverse events,” said G. Caleb Alexander, a drug protection expert and a professor at the Johns Hopkins Bloomberg School of Public Health.
In the onslaught of COVID-19 trials, many well-intentioned researchers were giving some of the same drugs — hydroxychloroquine and other repurposed medications — to thousands of people, tying up resources in an effort to answer the same questions. Worse, they were doing it in ways that might not accomplish that and could delay the quest to find viable treatments.
Avoiding the go-it-alone approach, the U.K. has made some of the most important COVID-19 drug research findings, in part because of coordinated research across its National Health System.
In June, University of Oxford researchers were the first to find a life-saving drug, the common steroid dexamethasone, which cut the death rate by one-third in COVID-19 patients on ventilators and by 20% in those getting supplemental oxygen. The trial involved more than 6,400 patients across the British health care system.
Earlier, Oxford researchers found that hydroxychloroquine provided no benefit to hospitalized COVID-19 patients. That trial was coordinated across the U.K. in 4,700 patients. That study also found that patients who got the drug were slightly less likely to be discharged from the hospital alive within 28 days and were slightly more likely to need ventilation.
Last month, Oxford researchers also found no benefit from the combination antiviral HIV drug lopinavir-ritonavir in a trial involving 5,000 hospitalized COVID patients. The drugs also were being studied in smaller trials in the U.S. and many others around the world.
The hydroxychloroquine story is being repeated with dozens of other drugs that have been repurposed to treat or prevent COVID-19, the Journal Sentinel analysis found. More than 400 COVID-19 studies were being conducted in the U.S. as of early July, according to the database ClinicalTrials.gov.
The site is updated through the U.S. National Library of Medicine, component of the National Institutes of Health. Simply ordering a check on the site does not mean that it has been evaluated or verified by the federal government.
Even before the pandemic, “there were many stupid little trials that weren’t very good,” said Jerry Avorn, a medical professor at Harvard Medical School and an expert on the drug exam in a large number of people. With COVID-19, less rigorous testing is more common.
This, in turn, led to a politicization of science, he said, as when the FDA used a fragile science to factor an emergency authorization for hydroxychloroquine on March 28 to revoke it less than 3 months later.
President Donald Trump promoted the drug from the beginning, and in May he said he took it to avoid getting COVID-19. Another supporter of the drug, President Jair Bolsonaro of Brazil, revealed this month that he had tested positive for COVID-19 and that he too was taking the drug.
The so-called non-conformal use of untested drugs would possibly seem somewhat compassionate, but it is based on the erroneous assumption that it would lead to being smarter than harmful, said Andre Kalil, a medical professor and infectious disease expert. University of Nebraska Medical Center. This is specific fear when a user is already with a disease like COVID-19. The addition of volatile drugs can also make them worse.
A survey conducted last month through the Heart Rhythm Society, for example, found that 17% of healthcare professionals in the table reported having patients using hydroxychloroquine or chloroquine for COVID-19 and developed an electrocardiogram result that put them at the greatest threat to come. up to a potentially damaging central rate.
Some doctors say that if a drug is used MMA outdoors and the patient dies, it is because of the disease, but if the patient lives, it is because of the drug, Kalil said.
“It’s not just fake, it’s dangerous,” he said, adding that such findings can only come from a controlled investigation.
A June article through Alexander and other Johns Hopkins researchers tested the first wave of U.S. clinical trials. He discovered that many were created in a way that limited their value.
They often lacked key features that led to aid purposes, such as the use of randomized equipment and placebos, either of which helps eliminate bias and makes the effects more useful. They found that two-thirds were so-called “open” trials in which participants and researchers knew who was receiving the drug.
“The world has never noticed such a complex and confusing wave of clinical activity,” Alexander said.
In the absence of coordination, hydroxychloroquine trials used other doses, the Journal Sentinel’s research revealed. Approximately part of all studies were known as active patient recruitment.
Some were set up to control the drug alone, while others included other medications or vitamins. Some used the preferred and blind technique in which patients and researchers did not know who was receiving the drug or a placebo; some don’t. Some used the gold standard, the random technique in which participants are divided by the possibility of eliminating bias; others don’t.
At least 12 of the 50 hydroxychloroquine trials analyzed through the Journal Sentinel were open trials. At least 24 fewer than 1,000 patients.
Most were not giant enough to be final or to load other agents to blur the conclusions.
Trials of 1,000 or more people are needed to succeed in the final conclusions. But a trial has been established in Utah to check hydroxychloroquine in three hundred patients; at a Hawaiian hospital, 350 patients; and at a Pennsylvania hospital, 400 patients.
A California test tested hydroxychloroquine one day as a way to save COVID-19 on physical care workers, but also added 12 weeks of C, D and zinc nutrients. A New York hospital studied hydroxychloroquine with zinc and added an antibiotic, either azithromycin or doxycycline.
A Kentucky study attempted to read about five other prospective Covid treatments. He read about hydroxychloroquine with azithromycin, but also with ivermectin, a medicine used to treat ascaris; as well as a Japanese drug that treats an inflamed pancreas; and a Chinese supplement known as caramel wormwood that can be served in the form of tea or coffee.
The American style consists of going alone, said Alex Spyropoulos, professor of medicine at Zucker Medical School in Hofstra/Northwell, New York. “It’s an individualistic style. They don’t like to play together. In a pandemic, it shows its flaws.”
But when individual hospitals begin their own trials, they face a swamp of legal, moral and logistical disorders that want to overcome, he said. Most importantly, they might not recruit enough patients to make the effects of the trial useful.
Spyropoulos, who oversees a clinical trial of anticoagulants in COVID patients, said the intentions were good. Many hospitals saw patients “die from left to right” and sought to do something, but the lack of national coordination meant that the faithful resources to establish the trials could have been wasted.
The U.S. government has contributed to coordinated trials through the National Institutes of Health.
In a review sponsored by 1,100 patients in 10 countries, the firm announced in April that the forwarded drug allowed hospitalized patients in an average of 11 days, compared to 15 days for which they won a placebo.
A few weeks after Oxford researchers discovered that there were no advantages with hydroxychloroquine, the National Institutes of Health failed an examination of hydroxychloroquine due to difficulties in recruiting a sufficient number of patients. The end came here just over a month after the announcement of the trial and when the lack of usefulness of hydroxychloroquine became apparent.
Around the same time, a study of a smaller firm concluded that there are no advantages for hospitalized patients of the drug.
But the lower-quality eruption in COVID-19 continues in the United States and around the world, according to a new article in Med magazine.
Wherever the studies were carried out, the maximum were monocentric trials that were blind, making them more vulnerable to bias and probably the maximum likely to be widely applicable, the authors concluded.
Researchers from the University of Texas Southwestern Medical Center reviewed 1,029 COVID-19 trials that were recorded worldwide, adding 185 in the United States, between January 23 and May 5. Hydroxychloroquine paved the way with 217 tests.
With the devastating impact of COVID-19 across the planet, international collaboration into promising treatments might have been expected, but that was not the case, the researchers found. Less than 3% of the trials involved collaborations across countries.
“It just seems like it was more of a waste of resources,” said lead author David Hsieh, an assistant professor of internal medicine at the university.