Medical ethics in pandemic times

https://www.axios.com/medical-ethics-clinical-trials-pandemic-eb77f819-76f1-45b0-af8a-cf181bc1607b.html

The Importance of Medical Ethics | Medical Ethics – theMSAG

The COVID-19 pandemic is rife with scientific and medical uncertainty, including debates about the ethics of using experimental treatments.

The big picture: As the global pandemic continues, the tension between providing the best available care for patients and performing trials to determine whether that care is effective risks complicating the medical response.

The big question: Is it unethical to withhold a possible treatment from someone who instead receives a placebo, or to continue to administer that treatment without having collected data on whether it works?

Driving the news: President Trump received an experimental monoclonal antibody cocktail via expanded access or “compassionate use,” which allows someone to access a treatment outside of a clinical trial before it is approved, provided their doctor, the drug company and the FDA agree.

  • Experts say his subsequent claims of the treatment being a cure risks reducing enrollment in clinical trials, flooding companies with requests for access to a limited number of doses and creating false hope for patients.
  • And the president’s treatment raised questions about fairness — would other COVID-19 patients have similar access?
  • “It’s important that we not say the president got access to a beneficial experimental intervention because we don’t know if it is beneficial or if there are adverse events associated with it, says Alex John London, director of the Center for Ethics and Policy at Carnegie Mellon University. 

He and other ethicists say the president’s treatment highlights a broader question about the ethical obligation doctors have to the science needed to determine if those treatments are effective.

Between the lines: Offering patients experimental COVID-19 drugs via emergency use authorizations, expanded access programs and compassionate use can slow needed clinical trials.

  • Researchers have struggled to enroll people in clinical trials in which they may receive a placebo if patients can access a drug directly.
  • One example: “There’s been some hiccups with the expanded access use for convalescent plasma, because it was something that precluded people from enrolling in a randomized control trial, so it took longer, and we still don’t quite know how well convalescent plasma works,” says Amesh Adalja, an infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security.

More than 100,000 COVID-19 patients at almost 2,800 U.S. hospitals received convalescent plasma from people who survived the virus and developed antibodies to it.

  • “It’s easy for people to say you enrolled 100,000 people, there should have been a trial. But a small number of those 2,800 hospitals would have been capable of doing those trials,” says the Mayo Clinic’s Michael Joyner, who leads the program.
  • There are now smaller trials taking place to answer questions about the effectiveness of plasma in treating the disease in different stages.
  • But if this happens again, Joyner says programs at academic medical centers should be peeled off earlier to form clinical trials run in parallel.

The gold standard for determining whether a treatment works is through randomized controlled trials in which people are randomly assigned to receive a treatment or to be in a control group.

  • In the uncertainty and urgency of a pandemic, some physicians argue randomizing people to receive a placebo goes against physicians’ ethics and that it is better to do something to help patients than do nothing.
  • “That’s a false dichotomy because the question is, what should we do?” says London.

From a doctor’s perspectiveit’s important to weigh the collective value of theearly drug data and the individual needs of the patient, Adalja says.

  • “I do think you have to be extra careful when you’re thinking about drugs that you don’t have strong randomized control trial data for, or the data is incomplete or inconclusive,” he adds.
  • “What people have to ask themselves is what constitutes evidence or proof and where do you want to make the bets in a pandemic?” says Joyner.
  • “There is a moral, legal and public health obligation to do those trials before people use those products,” says Alison Bateman-House, a professor of medical ethics at NYU’s Grossman School of Medicine who co-chairs an international working group on pre-approval access to treatments.
  • She says she understands the emotional pull on doctors to help patients whose health is quickly deteriorating, “but it is not evidence-based medicine.”

“There is no ethical obligation to give anyone an unproven substance.”

Alison Bateman-House, NYU Grossman School of Medicine

In a forthcoming paper, London argues that when medical professionals don’t have the knowledge they need to treat patients, it is their responsibility “to band together and run studies to get evidence to discharge [their] very ancient medical obligation.”

  • Medical ethics should be updated to include a responsibility to learn in the face of uncertainty, says London, who was part of a committee that called for research to be incorporated into the response to the Ebola outbreak in West Africa in 2014.
  • The U.K.’s large randomized RECOVERY trial is based in part on the Ebola experience, says London. “Because of it, we know dexamethasone is effective and hydroxychloroquine is not.”

What to watch: How the FDA’s handling of treatments during the pandemic influences other drugs and diseases once the pandemic ends.

The bottom line: “Medicine doesn’t have a good handle on uncertainty, and that is a problem,” says London.

Inside the epic White House fight over hydroxychloroquine

https://www.axios.com/coronavirus-hydroxychloroquine-white-house-01306286-0bbc-4042-9bfe-890413c6220d.html

Huge fight breaks out among White House coronavirus task force ...

The White House coronavirus task force had its biggest fight yet on Saturday, pitting economic adviser Peter Navarro against infectious disease expert Anthony Fauci. At issue: How enthusiastically should the White House tout the prospects of an antimalarial drug to fight COVID-19?

Behind the scenes: This drama erupted into an epic Situation Room showdown. Trump’s coronavirus task force gathered in the White House Situation Room on Saturday at about 1:30pm, according to four sources familiar with the conversation. Vice President Mike Pence sat at the head of the table.

  • Numerous government officials were at the table, including Fauci, coronavirus response coordinator Deborah Birx, Jared Kushner, acting Homeland Security Secretary Chad Wolf, and Commissioner of Food and Drugs Stephen Hahn.
  • Behind them sat staff, including Peter Navarro, tapped by Trump to compel private companies to meet the government’s coronavirus needs under the Defense Production Act.

Toward the end of the meeting, Hahn began a discussion of the malaria drug hydroxychloroquine, which Trump believes could be a “game-changer” against the coronavirus.

  • Hahn gave an update about the drug and what he was seeing in different trials and real-world results.
  • Then Navarro got up. He brought over a stack of folders and dropped them on the table. People started passing them around.
  • “And the first words out of his mouth are that the studies that he’s seen, I believe they’re mostly overseas, show ‘clear therapeutic efficacy,'” said a source familiar with the conversation. “Those are the exact words out of his mouth.”

Navarro’s comments set off a heated exchange about how the Trump administration and the president ought to talk about the malaria drug, which Fauci and other public health officials stress is unproven to combat COVID-19.

  • Fauci pushed back against Navarro, saying that there was only anecdotal evidence that hydroxychloroquine works against the coronavirus.
  • Researchers have said studies out of France and China are inadequate because they did not include control groups.
  • Fauci and others have said much more data is needed to prove that hydroxychloroquine is effective against the coronavirus.
  • As part of his role, Navarro has been trying to source hydroxychloroquine from around the world. He’s also been trying to ensure that there are enough domestic production capabilities inside the U.S.

Fauci’s mention of anecdotal evidence “just set Peter off,” said one of the sources. Navarro pointed to the pile of folders on the desk, which included printouts of studies on hydroxychloroquine from around the world.

  • Navarro said to Fauci, “That’s science, not anecdote,” said another of the sources.

Navarro started raising his voice, and at one point accused Fauci of objecting to Trump’s travel restrictions, saying, “You were the one who early on objected to the travel restrictions with China,” saying that travel restrictions don’t work. (Navarro was one of the earliest to push the China travel ban.)

  • Fauci looked confused, according to a source in the room. After Trump imposed the travel restrictions, Fauci has publicly praised the president’s restriction on travel from China.
  • Pence was trying to moderate the heated discussion. “It was pretty clear that everyone was just trying to get Peter to sit down and stop being so confrontational,” said one of the sources.
  • Eventually, Kushner turned to Navarro and said, “Peter, take yes for an answer,” because most everyone agreed, by that time, it was important to surge the supply of the drug to hot zones.
  • The principals agreed that the administration’s public stance should be that the decision to use the drug is between doctors and patients.
  • Trump ended up announcing at his press conference that he had 29 million doses of hydroxychloroquine in the Strategic National Stockpile.

Between the lines: “There has never been a confrontation in the task force meetings like the one yesterday,” said a source familiar with the argument. “People speak up and there’s robust debate, but there’s never been a confrontation. Yesterday was the first confrontation.”

  • In response to a request for comment on Axios’ reporting, Katie Miller, a spokesperson for the vice president, said: “We don’t comment on meetings in the Situation Room.”

The bottom line: The way to discuss the drug’s potential has become a fraught issue within the Trump administration.

  • Most members of the task force support a cautious approach to discussing the drug until it’s proven.
  • Navarro, on the other hand, is convinced based on his reading that the drug works against the coronavirus and speaks about it enthusiastically.
  • Some of Trump’s favorite TV hosts, including Fox’s Sean Hannity, and friends including Rudy Giuliani, have also been touting the malaria drug for the coronavirus. Trump has made no secret who he sides with.
  • “What do you have to lose? Take it,” the president said in a White House briefing on Saturday. “I really think they should take it. But it’s their choice. And it’s their doctor’s choice or the doctors in the hospital. But hydroxychloroquine. Try it, if you’d like.”