Lessons Learned — or Not — from Hydroxychloroquine Mishap
Public trust is hard to regain
The research community’s decades of work to build public trust in IRB oversight and the clinical trial process has reached one of its greatest challenges during the COVID-19 pandemic.
Misinformation spread through social media and some media outlets, as well as contradictory instructions and information from political and public health officials, have helped create distrust. When government agencies then take actions that some people believe are more politically motivated than evidence-driven, trust wavers.
For example, in mid-March, President Trump issued tweets promoting the antimalarial and lupus drug hydroxychloroquine as a treatment for COVID-19, based on a tiny French study. That study was quickly followed by other research showing no difference between hydroxychloroquine and placebo. Based on the findings, New York Gov. Andrew Cuomo signed an executive order in late March, instructing pharmacists not to dispense hydroxychloroquine as a COVID-19 treatment.1
Through the spring of 2020, misinformation about hydroxychloroquine as a COVID-19 therapeutic proliferated after President Trump spoke about it as a cure, says Tim K. Mackey, MAS, PhD, associate professor at the University of California, San Diego School of Medicine and director of healthcare research and policy at UC San Diego Extension. Rumors circulated on social media that a couple connected to hydroxychloroquine manufacturing were murdered because they promoted the drug as a cure, Mackey notes.
“There was some weird stuff,” he adds. “One tweet said you don’t need a vaccine or mask because hydroxychloroquine works.”
Trump continued to promote the drug as a cure through April. In May, he said he was taking daily doses of hydroxychloroquine, presumably to prevent COVID-19.2
The Centers for Disease Control and Prevention (CDC) reported new prescriptions for hydroxychloroquine or chloroquine in March 2020 were 7.2 times higher than those in March 2019. New prescriptions in April 2020 were 3.3 times higher than in April 2019.3
The Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for oral formulations of hydroxychloroquine sulfate on March 28. The EUA enabled distribution of the drug from the Strategic National Stockpile as a treatment for COVID-19. But on June 15, the FDA revoked its EUA, citing scientific evidence that showed the product did not meet EUA criteria for evidence-based effectiveness and benefits that outweigh risks.4
“Recent data from a large randomized controlled trial showed no evidence of benefit for mortality or other outcomes such as hospital length of stay or need for mechanical ventilation of HCQ treatment in hospitalized patients with COVID-19,” the FDA letter says.4
The FDA’s reversal suggests the agency should make improvements in its EUA process, according to the authors of a recent editorial, published in JAMA.5
During a public health crisis, like the COVID-19 pandemic, federal agencies might need to expedite their decision-making process, but they should be cautious of political influence.
“On the one hand, this is the most devastating public health pandemic of our lifetime, and we need to solve it efficaciously,” says Herschel Nachlis, PhD, research assistant professor of government and policy fellow in the Rockefeller Center for Public Policy and Social Sciences at Dartmouth College in Hanover, NH. “On the other hand, we have less than precise regulatory standards. The FDA learned the hard way with hydroxychloroquine because the last thing you want to do is put a product out there for consumers to use and then say, ‘We’re wrong. We shouldn’t have let that product out there.’”
One of the problems is the FDA has rarely issued EUAs for anything except diagnostic tests. The only vaccine ever made available through an EUA was for anthrax — and that vaccine already was on the market, Nachlis notes.
“A lot of people are saying we need to make these EUA standards clear and more transparent for the future,” he says.
If the FDA had waited a couple of months before issuing an EUA for hydroxychloroquine, it would have had data from every study, showing that it did not appear to have any effect on mortality and morbidity. Encouraging hospitals to use hydroxychloroquine with almost no positive data wasted everyone’s time: “It took bandwidth away from running trials on other things,” Nachlis says.
When everyone is focused on one possible cure that ends up not working, it ties up resources that could have been devoted to therapeutics that might work well, he adds.
“It’s really sorry to watch the fate of hydroxychloroquine because it was a false hope,” says Susan E. Lederer, PhD, professor of medical history and bioethic at the University of Wisconsin–Madison in Madison. The public desperation for a cure is understandable and true of past epidemics, she says.
“When people were harmed by cholera in the 19th century, they’d try anything,” Lederer says. “It was a disease killing large numbers of people, and they’d try smoke enemas.”
But in the 21st century, treatments need to be evidence-driven. “We want to make sure they’re not hurting people by giving interventions that are unsafe and might have hastened long-term disability,” Lederer says.
This misstep could have been avoided. It has caused public skepticism toward the FDA, says Alison Bateman-House, MPH, PhD, assistant professor in the division of medical ethics at NYU Grossman School of Medicine in New York City.
“We’re already in a situation where people are leery of what is happening at the FDA,” she says.
The CDC also came under question by scientists and public health officials who claimed the agency was becoming more political under the influence of appointees at the U.S. Department of Health and Human Services. Some health officials claimed Trump appointees and partisans delayed Morbidity and Mortality Weekly Reports.6
The hydroxychloroquine mistake was followed up by the FDA issuing an EUA for COVID-19 plasma as a treatment, despite incomplete clinical trials. National news reports noted the FDA gave emergency approval for COVID-19 blood plasma after bowing to pressure from President Trump.7 Then, Trump told the public that a coronavirus vaccine could be available by 2020 Election Day, and the FDA followed this up with letters to states, asking them to prepare for a vaccine by Nov. 1.8
“I just saw that the FDA commissioner sent out an email to all staff, promising that he would not interfere with a data-driven decision, and he has been on a tour of FDA divisions to say that in person,” Bateman-House says. “It’s a shame that this cleanup is having to happen because of public missteps that could have been avoided.”
The formerly sterling reputation of the FDA has suffered from these blows. Combined with the antivaccination movement and the president’s accusation that the FDA has slow-walked COVID-19 therapies and vaccine research, there is a toxic confluence of circumstances that could affect how the public views an eventual vaccine when it is approved, she explains.
“The idea is that a vaccine will get things back to normal. Even a 100% effective vaccine — there never has been one — will not get us to those desired results if people do not take it,” Bateman-House says. “If people don’t trust it, they won’t take it.”
Public trust in scientists and what science shows was on the rise through 2019. Results of a Pew Research Center study showed Americans had growing confidence in science, rising from 76% in 2016 to 86% in 2019.9 A different Pew survey from May 21 revealed trust in scientists is growing in the United States, but mostly among Democrats.10
Scientists and public health officials are at a disadvantage in communicating their research findings through the social media filter. “It’s much easier to say ‘A drug works’ if someone is scared about COVID and to say ‘You can be cured,’ than it is to explain, ‘The FDA revoked its emergency use authorization, and here’s why,’” Mackey notes. “The messaging for misinformation is so much easier and impactful than the public health response. When you’re not bound by evidence or scientific facts, it’s much easier to communicate.”
President Trump understands how to communicate to certain audiences, and misinformation created in that wave is much more cognizant, Mackey adds.
Public erosion in trust of governmental scientists and public health officials could result in a failed coronavirus vaccine campaign, even if one of the vaccine trials succeeds. “If you have that concern about the scientific validity of the vaccine approval, then it will, of course, be picked up by the larger, antivaccine movement with people saying, ‘This is what we’ve been warning you about all along,’” says Bateman-House.
“You will have a situation in which you have people already opposed to vaccines feel validated, and people who formerly were very big supporters of vaccines saying, ‘I’m for vaccines, but not this vaccine,’” she adds. “This is the foreseeable outcome of a politicized rush.”
While some people still will opt for the vaccine, the damage will be done. The potential benefits of national public health campaign to get people vaccinated against SARS-CoV-2 will be lost.
“This could transform access to all vaccines,” Bateman-House adds.
- Herper M. What if hydroxychloroquine doesn’t work? What if it does? Right now, we don’t know. Stat, March 27, 2020. https://www.statnews.com/2020/03/27/we-dont-know-hydroxychloroquine/
- Carvajal N, Liptak K. Trump says he is taking hydroxychloroquine though health experts question its effectiveness. CNN, May 19, 2020. https://www.cnn.com/2020/05/18/politics/donald-trump-hydroxychloroquine-coronavirus/index.html
- Bull-Otterson L, Gray EB, Budnitz DS, et al. Hydroxychloroquine and chloroquine prescribing patterns by provider specialty following initial reports of potential benefit for COVID-19 treatment — United States, January-June 2020. MMWR Morb Mortal Wkly Rep 2020;69:1210-1215.
- Food and Drug Administration. Letter revoking EUA for chloroquine phosphate and hydroxychloroquine sulfate, June 15, 2020. https://www.fda.gov/media/138945/download
- Thomson K, Nachlis H. Emergency use authorizations during the COVID-19 pandemic: Lessons from hydroxychloroquine for vaccine authorization and approval. JAMA 2020; doi: 10.1001/jama.2020.16253. [Online ahead of print].
- Weiland N, Stolberg SG, Goodnough A. Political appointees meddled in the CDC’s “holiest of the holy” health reports. The New York Times, Sept. 15, 2020. https://www.nytimes.com/2020/09/12/us/politics/trump-coronavirus-politics-cdc.html?campaign_id=2&emc=edit_th_20200913&instance_id=22153&nl=todaysheadlines®i_id=43012034&segment_id=37964&user_id=dcf13f00af010f5aab24b0ea015a94e8
- LaFraniere S, Weiland N, Shear MD. Trump pressed for plasma therapy. Officials worry, is unvetted vaccine next? The New York Times, Sept. 12, 2020. https://www.nytimes.com/2020/09/12/us/politics/trump-coronavirus-treatment-vaccine.html?campaign_id=2&emc=edit_th_20200913&instance_id=22153&nl=todaysheadlines®i_id=43012034&segment_id=37964&user_id=dcf13f00af010f5aab24b0ea015a94e8
- Kaplan S, Wu KJ, Thomas K. CDC tells states how to prepare for COVID-19 vaccine by early November. The New York Times, Sept. 2, 2020. https://www.nytimes.com/2020/09/02/health/covid-19-vaccine-cdc-plans.html
- Funk C, Hefferon M, Kennedy B, et al. Trust and mistrust in Americans’ views of scientific experts. Pew Research Center, Aug. 2, 2019. https://www.pewresearch.org/science/2019/08/02/trust-and-mistrust-in-americans-views-of-scientific-experts/
- Funk C, Kennedy B, Johnson C. Trust in medical scientists has grown in the U.S., but mainly among Democrats. Pew Research Center, May 21, 2020. https://www.pewresearch.org/science/2020/05/21/trust-in-medical-scientists-has-grown-in-u-s-but-mainly-among-democrats/
The research community’s decades of work to build public trust in IRB oversight and the clinical trial process has reached one of its greatest challenges during the COVID-19 pandemic. Misinformation spread through social media and some media outlets, as well as contradictory instructions and information from political and public health officials, have helped create distrust. Through the spring of 2020, misinformation about hydroxychloroquine as a COVID-19 therapeutic proliferated after President Trump spoke about it as a cure.
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