Some in Ebola trials wouldn't get drugs under plan
U.S. health officials want some patients to forgo potentially life-saving Ebola treatments when they're being tested so researchers can compare their response to those who get the medicines, said an official involved in the discussions.
Some experimental drugs have already been used on an emergency basis. In a formal trial, the U.S. wants one group of patients to get the treatments and a second to get only standard supportive care, said the official, who asked not to be identified because the person isn't authorized to speak on the record. Supportive care includes replacing fluids and using medicines to fight off other infections.
The Food and Drug Administration oversees trials that generate data for approval of medical products. Many of the Ebola trials may be done in Western Africa, where an outbreak has killed more than 4,400 in Liberia, Sierra Leone and Guinea.
"At the moment, it is just so urgent to figure out what works and what doesn't work, and to do it with a reasonable degree of certainty," said Steven Joffe, at the University of Pennsylvania's department of medical ethics and health policy.
Companies working on treatments include FujiFilm Holdings Corp., Mapp Biopharmaceutical Inc., Tekmira Pharmaceuticals Corp., and Chimerix Inc.
Trials where everyone gets an experimental drug may be misleading, making doctors think a treatment is more or less effective than it actually is. It could also mask harm in critically ill patients.
Fauci's View
"It is important to balance the urgency to deploy investigational medical countermeasures in an emergency such as the current Ebola outbreak with the need to ensure the maximal safety and to determine the efficacy of candidate drugs and vaccines for Ebola," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said in prepared testimony for a congressional hearing today.
"Randomized controlled clinical trials remain the 'gold standard' for the evaluation of candidate drugs and vaccines because they represent the most efficient way to prove efficacy and lack of an unexpected harmful effect," Fauci added.
The idea of using placebos for some in West Africa instead of the drugs has created a firestorm of controversy as scientists debate the ethics of pitting one of the world's deadliest pathogens against the need to better understand exactly which drugs are most effective.
Ethicists Object
Seventeen medical ethicists and health providers from across the world last week denounced efforts to require randomized controlled trials that don't give the therapies to everyone. The lack of effective treatments for Ebola, its high mortality and poor infrastructure where it is prevalent means novel approaches are needed, they wrote in the journal Lancet.
"We accept that randomized controlled trials can generate strong evidence in ordinary circumstances," said the authors, who included top researchers and doctors from the University of Oxford in the U.K., NYU Langone Medical Center in New York and elsewhere. "Not, however, in the midst of the worst Ebola epidemic in history."
Scott Gottlieb, a former deputy commissioner at the FDA, agreed. 'It's really unfortunate that they can't think creatively about how to structure trials that allow them to make appropriate observations without randomizing people to die,'' said Gottlieb, who is now a researcher at the nonprofit American Enterprise Institute in Washington.
"We have a deadly virus, you can easily observe a clinical effect and many of the drugs are widely understood," he said in a telephone interview.
The drugs aren't at the point of being tested for effectiveness, which is typically the last of the three stages of trials required before approval.
The FDA is seeking to speed the Ebola treatments through development, by making trials smaller and faster, according to the U.S. official. If a drug works well, regulators could quickly move patients into the group getting it, the person said.
The U.S. is also concerned that patients in trials get the best level of care possible, which could be tough given the devastated health infrastructure in the most-affected countries in West Africa, the official said.
GlaxoSmithKline Plc is conducting U.S.- and U.K.-based safety trials of a vaccine for Ebola. Safety trials have also started for NewLink Genetics Corp.'s vaccine for the virus.
Chimerix's brincidofovir is a version of the drug cidofovir, used for years to treat an infection linked to HIV, that has been slightly altered to reduce its side effects. Thomas Eric Duncan, the Liberian man who died of the disease in Dallas, got Chimerix's drug during his treatment, as did one other man in Nebraska. Fujifilm's Avigan is approved in Japan for influenza and is in advanced testing in the U.S.
Patients in the U.S. who have lived have received experimental drugs from Mapp, based in San Diego, and Tekmira, based in Canada, though it's unclear if the drugs were the reason why.