Amid Hydroxychloroquine Uproar, Real Studies of Drug Are Suffering

By Sheryl Gay Stolberg

WASHINGTON — President Trump’s enthusiastic embrace of a malaria drug that he now says he takes daily without proof that it is effective against Covid-19 — and the resulting uproar in the news media — appears to be interfering with legitimate scientific research into whether the medicine might work to prevent coronavirus infection or treat the disease in its early stages.

The drug, hydroxychloroquine, which is also widely used to treat lupus and other autoimmune diseases, has shown no real benefit for hospitalized coronavirus patients, and may have contributed to some deaths, recent studies show. Some bioethicists are even calling for the Food and Drug Administration — which has warned that the drug can cause heart problems — to revoke an emergency waiver it granted in March to accept millions of doses of hydroxychloroquine into the national stockpile for use in hospitals.

But specialists — including Dr. Anthony S. Fauci, the government’s top infectious disease expert — say the jury is still out on whether the drug might help prevent infection or help patients avoid hospitalization. Mr. Trump’s frequent pronouncements and misstatements — he has praised the drug as a “game changer” and a “miracle” — are only complicating matters, politicizing the drug and creating a frenzy in the news media that is impeding research.

“The virus is not Democrat or Republican, and hydroxychloroquine is not Democrat or Republican, and I’m just hopeful that people would allow us to finish our scientific work,” said Dr. William O’Neill, an interventional cardiologist at Henry Ford Hospital in Detroit, who is studying hydroxychloroquine as a prophylactic in health care workers.

“The worst thing in the world that would happen,” he added, “is that at the end of his epidemic, in late September, we don’t have a cure or a preventive because we let politics interfere with the scientific process.”

On Tuesday, Mr. Trump added to the uproar. Addressing reporters on Capitol Hill, he called the research on hospitalized patients “a Trump enemy statement.” Later, at the White House, he said he decided to take hydroxychloroquine after his valet tested positive for Covid-19 — and intended to do so for “a little while longer” because he viewed it as a “worthwhile line of defense” and was “very curious” about it.

“It’s gotten a bad reputation only because I’m promoting it,” the president added. “If anybody else were promoting it, they would say it’s the best thing ever.”

Last week, the National Institute of Allergy and Infectious Diseases, which Dr. Fauci leads, announced a 2,000-patient study to determine whether hydroxychloroquine, when combined with the antibiotic azithromycin, “can prevent hospitalization and death from Covid-19,” joining more than 50 other clinical trials involving hydroxychloroquine that are continuing in the United States.

UnitedHealth Group is conducting a much smaller study of hydroxychloroquine alone, but Dr. Deneen Vojta, the insurance giant’s executive vice president for research and development, said the controversy was depressing enrollment in their clinical trials.

“People who had already enrolled would say, ‘Now I’m afraid, I want to disenroll,’” Dr. Vojta said.

In a draft letter to the Journal of the American Medical Association, obtained by The New York Times, members of a research consortium complained that “negative media coverage” of hydroxychloroquine — in particular the studies showing it might have harmed hospitalized patients — “directly correlated” with a drop in enrollment in trials run by institutions including the University of Minnesota, the University of Washington, Columbia University in New York and Henry Ford Hospital.

“Healthy fear stimulates scientific discoveries; uncontrolled fear inhibits scientific advancements,” the researchers wrote. “Politics and sensationalized journalism must not interfere with the integrity of much needed clinical trials.”

Inside the White House, the president’s trade adviser, Peter Navarro, who is an enthusiast for hydroxychloroquine and has worked with the Federal Emergency Management Agency to steer 19 million pills from the stockpile to 14 coronavirus hot zones around the country, said “hydroxy hysteria” in the news media — not Mr. Trump — was to blame.

“Has the media’s war of hysteria on hydroxychloroquine killed people?” Mr. Navarro asked in an interview. “If the scientific evidence does indeed prove that the medicine has both prophylactic and therapeutic value, the answer is yes.”

While Mr. Navarro complained that “fake news and bad reporting” had resulted in a “dramatic drop in demand for hydroxy at hospitals,” Dr. Mitchell Katz, the president and chief executive of NYC Health and Hospitals, the nation’s largest municipal health system, said hospitals and doctors became less interested in hydroxychloroquine after the F.D.A. approved another medicine, remdesivir, for treatment of Covid-19.

But Mr. Trump continued to champion hydroxychloroquine, prompting criticism even from his favorite television network: Fox News Channel, whose senior managing editor for health news, Dr. Manny Alvarez, called the president “highly irresponsible” for taking the drug.

Scientists have worried about politics impeding their research since long before Mr. Trump took office. But perhaps no president in modern history has gone to the lengths that Mr. Trump has to promote a specific, unproven medicine — and then announce he is taking it himself. Many experts are aghast.

“What I am concerned about is that it may lead people to overestimate the potential that it would help them — which is entirely unproven — and to underestimate the risks, which are known,” said Jesse L. Goodman, a former chief scientist at the F.D.A. who is calling for the agency to revoke its waiver. “I think that right now this drug should be used really only in the context of clinical trials.”

But the president’s promotion of the drug is making even that difficult. Dr. Adrian Hernandez, who directs the Clinical Research Institute at Duke University School of Medicine and has enrolled 550 health care workers in a clinical trial to study whether hydroxychloroquine is effective as a prophylactic, said Mr. Trump’s promotion of hydroxychloroquine “may have hurt public health.”

When Mr. Trump first began talking up hydroxychloroquine, Dr. Hernandez said, he faced questions about whether his study should be weighted toward giving the drug to more people than were receiving placebo. But the pendulum swung the other way, he said, after two studies showed ill effects.

When he started, he said, two-thirds of more than 12,000 health care workers who have signed up for a coronavirus registry were willing to participate in his study. Now, only half are.

“When we have this playing out in the media instead of the scientific and clinical communities, people don’t know what the right answer is, and so they will use what they hear the most through the media,” Dr. Hernandez said. “So it’s a Ping-Pong match, in terms of, is it good one day? Is it bad one day?”

Dr. Hernandez and others, including Dr. O’Neill, say that no study — even those conducted in hospitalized patients — has produced definitive results about hydroxychloroquine for the coronavirus, though several have suggested it could be harmful especially to patients with underlying heart conditions.

An analysis of veterans treated with hydroxychloroquine found that 28 percent of them died, compared with 11 percent who had routine care. Mr. Trump denounced it on Tuesday as the work of his enemies. A small study in Brazil of patients taking a high dose of chloroquine — a predecessor to hydroxychloroquine that researchers consider less safe — was stopped for safety reasons.

Dr. Christine Johnston, an associate professor of medicine at the University of Washington who is hoping to enroll 630 people in a trial examining the effectiveness of hydroxychloroquine in those recently infected, said many of her patients conflated the Brazil study with her drug. She, too, has seen a dip in enrollment.

“People put these things together in their minds but they are actually very different,” she said.

On April 24, the F.D.A. issued a warning about hydroxychloroquine and chloroquine, cautioning against their use “outside of the hospital setting or a clinical trial due to risk of heart rhythm problems.” An F.D.A. spokesman, Michael Felberbaum, said in a statement that the agency was continuing to evaluate its emergency use authorizations, or E.U.A.s, issued because of “the current public health emergency, including the E.U.A. regarding chloroquine and hydroxychloroquine, to determine whether they continue to meet the statutory criteria for issuance.”

More recently, a large observational study of 1,446 patients at NewYork-Presbyterian-Columbia University Hospital in New York City, published this month in the New England Journal of Medicine, found no clear benefit or risk to hydroxychloroquine.

The authors concluded that randomized controlled clinical trials — studies in which half the patients are given placebo, half are given the drug and neither the patients nor doctors know who is getting what — are needed.

“Studying it is exactly the right thing to do,” said Aaron S. Kesselheim, a professor of medicine at Harvard Medical School who is among those calling for the F.D.A. to revoke the waiver. “I don’t mind doing a well organized, definitive clinical trial. I think that would be very helpful. And heck if it turns out there is some activity then great. Then in that case we should figure out how to get to the people who need it as quickly as possible.”

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