In early April, Sonja Gill, a rheumatologist in Oakville, Ontario, began to get unreliable inquiries from patients with lupus or rheumatoid arthritis that she treated. They tried to fill the regular prescription of hydroxychloroquine, an antimalarial drug that can alleviate the symptoms of these two autoimmune diseases, but their pharmacist said they did not.
"We have come one by one, one by one," said Gil, who estimates that 70% of her 1,500 patients take hydroxychloroquine. She asked the administrative assistant to work with pharmacies and wholesalers to find supplies.
"If not, [switching to another medication] is a difficult decision," Jill said. "The most difficult part is telling the patient what to do."
There is little mystery about the cause. In the weeks of early April, President Donald Trump and the American media chorus continued to discuss and publish how a generic drug, hydroxychloroquine, became a miracle therapy for coronaviruses, which allegedly reduced the virus levels of infected patients, thereby Speed up recovery.
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"They are not blind," Gil said of her patient. "All these things have been on TV since Trump tweeted." Suddenly, the drug was added to the list of ominous goods – toilet paper, Lysol wipes, flour, yeast, masks And more – experienced shortages related to the pandemic. The result: Gil ’s patient became an unwitting victim of Trump ’s scientific war.
The legend of hydroxychloroquine subsided after death at an overdose, but has stumbled recently. Trump claims that he is taking this drug to defend against COVID-19, which is in science, social media, politics and the global supply chain Unpredictable conflicts occurred in this crisis.
When reports of initial discoveries about treatments and vaccines were widely disseminated, they not only stimulated public expectations. The propaganda caused a chain reaction that caused confusion within the pharmaceutical companies where regulators, doctors' offices and even in some cases were forced to compete to meet growing demand.
In addition, the story of hydroxychloroquine-coronavirus is not over. Some experts strongly opposed the use of hydroxychloroquine, including Richard Bright, a doctor who led the US Federal Agency for Advanced Research and Development in Biomedicine, who was dismissed by Trump for his outspokenness. On May 22, the peer-reviewed medical journal "The Lancet" published a study examining the various arrangements of hydroxychloroquine and antibiotics for 15,000 COVID-19 patients in nearly 700 hospitals reaction. Key takeaway: Patients have an increased risk of arrhythmia, indicating that these treatments “are ineffective and may be harmful to hospitalized COVID-19 patients.”
Despite increasing evidence, international randomized controlled trials are currently under way A large number of clinical studies have been conducted on the safety and effectiveness of the drug. Its researchers include doctors in teaching hospitals in Ontario, Nova Scotia, Manitoba and Alberta, as well as hundreds of Canadians. COVID-19 The patient is or will be participating. If these long-term studies support the use of hydroxychloroquine, then the Canadian market may face severe turbulence and shortages.
Unlike the US Food and Drug Administration, Health Canada does not allow doctors to use hydroxychloroquine alone or in combination with antibiotics to relieve COVID-19 symptoms. But before the president stepped into the competition, people's medical interest in the drug began to spread. Researchers such as Kevin Kain, MD, of the University of Toronto Health Network and Chairman of the Canadian Infectious Disease Research Institute, have been studying in research laboratories for several years. These studies have demonstrated the antiviral properties of an effective ingredient in hydroxychloroquine.
In early March, he joined an international team to establish a "double-blind, placebo-controlled" randomized clinical trial (gold standard) to study the potential for the prophylactic use of the drug in front-line medical staff. Kane said: " This was before Trump poisoned the waters with the wrong information and released a poor quality" research "from France.
French Studies online Published in International Anti-microbial Agents involving 42 patients, which was subsequently released by Trump. Among the patients receiving medication, the former claimed that they showed a “significant reduction” in infections, although in the end ’S comment admits that the results are“ preliminary. ”( The New York Times recently published the lead researcher, a charming named Didier Raoult (Didier Raoult) The hard proposition of a microbiologist questioned his early research.]
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A person does not need a Ph.D. It is known that such a small sample will not produce definite results. Sunit Das, an associate professor of medical ethics at the University of Toronto Ethics Center, pointed out that the French paper says that this is a case The study used "level – three evidences", which is a term understood by medical researchers. Das said: "This is not evidence to promote clinical treatment."
However, Kane (Kain) went further and thought that the French paper was "a holy work that should not have been published." (Dass disagrees.) But the truth is that it was published online on a journal website without a paid column. It means that anyone can use these findings. A study in the Journal of the American Medical Association analyzed the Internet search for hydroxychloroquine, showed the French study was published with The steep slope at the beginning of the tweet coincides. Written by Elon Musk and approved by Trump in mid-March.
Another pair of small studies in Conducted in Brazil another study conducted in in several veteran hospitals in the United States came to the opposite conclusion: hydroxychloroquine was ineffective or unsafe. Kain said these findings – One was based on 81 cases and the other was based on 368 cases –which caused a strong response. They informed the deported US officials Richard Bright of derogatory comments. (The study of 1,466 people who were admitted to the ER and accepted COVID-19 in in the New England Journal of Medicine was inconclusive.]
In high-dose treatment , And not even one is peer-reviewed before going live. Kane said that almost all drugs consumed in large quantities are poisonous. He also emphasized that the goal as a scientist is not to prove that hydroxychloroquine is a miracle therapy, but to answer questions about its efficacy clearly and strictly.
Health Canada is allowing anyone to receive COVID treatment at the hospital-19 to participate in one of the many clinical trials currently underway. Researchers in Canada and the United States say that due to sensational media reports that people are taking high doses of hydroxyl Chloroquine will die later, so it is difficult to recruit participants. Although the drug does have side effects on the heart, kidney and liver, Kain pointed out that doctors have used it safely for 70 years, so it is not difficult for researchers to conduct well-structured tests to ensure an appropriate dose.
In late March, Mint Pharmaceuticals, a manufacturer of generic drugs in Mississauga, Ontario, distributed 60% of all hydroxychloroquine used in Canada. The wholesaler received two very large The order provides medicine for the hospital. The order is equivalent to all hydroxychloroquine used in Canada in 2019 and has caused alarm bells.
Just a few days ago, the US Food and Drug Administration made a controversial decision and subsequently criticized decision to allow doctors to use hydroxychloroquine with antibiotics to treat COVID-19.
Federal officials in Ottawa began to monitor the situation and negotiated with Canadian suppliers during a weekly "stakeholder" conference call. At the time, no one knew why hospitals in Canada had stockpiles, but huge orders increased the prospect that "legacy" patients (patients with lupus or rheumatoid arthritis) might not be able to prescribe.
According to Jaiveer Singh, CEO of Peppermint, this fast-growing company has been manufacturing and distributing hydroxychloroquine in Canada since 2014, and the drug's revenue in 2019 was approximately $ 7 million. Mint is not the only generic drug company that distributes the drug in Canada, but competition in recent years has shrunk. Some global companies have abandoned the product in Canada because the current prices set by provincial drug prescriptions – have dropped, and are now much lower than hydroxychloroquine in the United States
cost. In late March, Singh warned Health Canada officials that those huge hospital orders may quickly absorb pharmacies that are commonly used to fill prescription drugs for patients with lupus and rheumatoid arthritis. "We are really worried," Singer said. He urged the government to issue large emergency orders to ensure that there is enough room. He said: "At that time, the federal government adopted a more cautious attitude. They did not want to increase inventory."
At that time, supply chain problems began to become more and more serious. Due to the pandemic, while the Canadian dollar plummeted, the cost of the active ingredient in the drug and the cost of transportation have risen. Singh said that if the company's costs exceed the prices set by the provinces, he fears that he will continue to supply the Canadian market.
Mint's partner for producing hydroxychloroquine is a large producer in India. As Singh said, India has become a pharmacy in the world. With the surge in global demand for the drug (in the wave of Trump's tweets) and the popularity of the Indian pandemic, the government of Indian Prime Minister Narendra Modi has closed the borders of drug exports, disrupting International supply chain.
Ottawa finally agreed to increase Canada ’s emergency patient warehouse in mid-April. After Singh, senior government officials and the Indian consulate in Toronto began to be busy ensuring that 5 million tablets were obtained from Mint ’s Indian suppliers. Exempt from export bans for rationalist reasons. The drugs arrived at the Mississauga warehouse in Mint in early May and were placed in cages monitored by closed-circuit cameras around the clock.
What about the big hospital orders that Mint must fill? Some of these tablets may be used in clinical trials currently underway in Canada. But we won't know the result until the second half of this year at the earliest. Singh said that if they prove that this ancient malaria drug can indeed treat COVID-19, then mint will increase production to serve the Canadian market. But the inevitable competition will bring other difficult choices: who should first understand this drug: patients with COVID-19 or patients with lupus and arthritis, they have to take a stronger alternative?
In addition to the details of the hydroxychloroquine story, this episode triggered – or a re-examination of – on the broader ethics of rapidly spreading semi-mature research to the hyperconnected world The problem can't wait to get rid of this virus.
About other premature discoveries – The latest report is News report there are eight modern biotechnology companies (a biotech giant with an annual turnover of 26 billion US dollars) Health companies have brought encouraging results. People injected with experimental vaccines – continue to find ways to enter the social media hurricane from the generally stagnant scientific literature ecosystem.
This dynamic has caused people to worry that these diseases will spread to the highest level of medical research institutions. " The pandemic inevitably leads to considerable morbidity, mortality and loss," New England Journal of Medicine believes. " Damage to the country's drug evaluation procedures and public respect for this should not be part of its legacy."
At the same time, rheumatologist Sonja Gill just hoped her patients would not face another round of orders The shortage of concern is due to the viral spread of research results that have not been properly scientifically reviewed.
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