Experts urge innovative ways to test new Ebola drugs

A group of influential medical and ethics experts today pushed for new ways to test new Ebola treatments, given the unprecedented situation in West Africa, and two high-level groups renewed their urgent pleas for countries to do more to help with the response.

In other developments, fallout from the Texas Ebola case continue, with the man's family continuing to question his care, and Spain hospitalized more people who had contact with a sick health worker for observation, while steps moved forward with vaccines.

In August a World Health Organization (WHO) expert panel asked to weigh in on experimental treatments said their use was ethical, but added there is a moral duty to conduct the best possible clinical trials in the context of the epidemic.

Signed by 17 scientists and other experts from three continents, the letter on treatment trials said insisting on randomized controlled trials (RCTs) for new Ebola drugs is unethical and impractical. The group made their case today in an early online edition of The Lancet. The authors include Peter Piot, MD, PhD, a London School of Hygiene and Tropical Medicine researcher who helped identify the Ebola virus in 1976; David Heymann, MD, a global health and infectious disease expert and board chair of Public Health England; and Arthur Caplan, director of the Division of Medical Ethics at New York University Langone Medical Center's Department of Population Health.

They wrote that although RCTs are the gold standard and provide strong evidence in most instances, the lack of treatment options for Ebola, high mortality with current care standards, and weak health systems in affected countries mean that global health leaders and drug developers should consider alternative trial designs.

Western medical workers who got the medication ZMapp weren't randomized to receive the drug or conventional care plus placebo, they wrote. "None of us would consent to be randomized in such circumstances."

They pointed out that there's no need to bend rules or cut corners on evaluating the new treatments, because different study designs have already been used to speed and ease the availability of new treatments to those with other deadly and dire conditions, such as cancer patients.

The main goal is to sift out which new drugs offer survival benefits, and the ones that do should be recommended by the WHO.

"We have innovative but proven trial designs for doing exactly that. We should be using them, rather than doggedly insisting on gold standards that were developed for different settings and purposes," they wrote.

More resource pleas, experts air 'black swan' analogy

Officials involved in West Africa's Ebola response have made two more urgent international requests for nations to step up their help in battling the outbreak, one at a World Bank session yesterday and one today before the United Nations (UN) General Assembly.

At a special meeting on Ebola at the World Bank in Washington, DC, yesterday, UN Secretary Ban Ki-moon said country contributions so far form the building blocks of a global response, the UN reported in a statement. He added that a 20-fold mobilization is needed, including more mobile laboratories, vehicles, protective gear, medical personnel, and evacuation capabilities.

Several of the top leaders involved in the outbreak response spoke today at a briefing on Ebola before the UN General Assembly, according to press release from the group. Anthony Banbury, who is leading the UN's special mission (UNMEER), told the group by video link from West Africa that the challenge is immense but it's not too late to win the battle. He called for strengthened treatment centers and diagnostic labs, more support for aid groups, and reliable arrangements for treating sick health workers.

In a related move, World Bank president Jim Yong Kim called for the creation of a new pandemic emergency facility that would rapidly respond to future outbreaks by delivering funds to countries in crisis. Though the focus for now needs to be on battling Ebola, planning must begin for the next pandemic that could have an even more devastating impact.

"The world has an IMF [international monetary fund] to coordinate and work with central banks and ministries to respond to financial crises," he said in a statement today. "When it comes to health emergencies, however, our institutional toolbox is empty: There's no such center of knowledge and skill for response and coordination."

David Nabarro, MD, special envoy of the Secretary-General on Ebola, warned that without a massive mobilization of resources from all parts of the globe, "it will be impossible to get this disease quickly under control, and the world will have to live with the Ebola virus forever."

In an opinion piece today, a group of global health and infectious disease experts said West Africa's Ebola epidemic is a "black swan" event that unlike any other disease threatens regional and country stability and exposes problems that undercut the WHO's ability to lead the response. A black swan event is a term coined in 2007 to describe high-profile, difficult-to-predict, rare financial events.

The first author of the viewpoint piece, published today in JAMA Internal Medicine, is Michael T. Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy, publisher of CIDRAP News. The coauthors include Kristine Moore, MD, MPH, CIDRAP's medical director, and Lawrence Gostin, JD, with the O'Neill Institute for National and Global Health Law at Georgetown University in Washington, DC.

Two of the outbreak's many lessons have changed the current thinking about infectious diseases, the group wrote. Given the disease's threat to the stability of the affected countries and the rest of Africa, global health leaders should think more creatively about future infectious disease scenarios and plan accordingly. "Researchers and public health officials should have and could have imagined what a virus such as Ebola that is transmitted through direct contact could do once it infected people outside of sparsely populated rural Africa and found its way into the crowded and impoverished neighborhoods of large African cities," they said.

They also assert that budget and staff cuts have eroded the WHO's resources and that without reforms, as well as adequate funding and authority from member states, WHO won't be able to fulfill its mandate to coordinate global health issues like the Ebola outbreak. The events could also usher in a stronger role for the United Nations to engage more in health threats, given the influence it has in raising the political will needed to battle such a massive event.

Liberian man's family raises more treatment questions

The family of a Liberian man who died from Ebola on Oct 8 in a Dallas hospital today raised more questions about the care he received, with the release of his 1,400 page medical record to the Associated Press (AP). During his first visit to the emergency department at Texas Health Presbyterian Hospital on Oct 26, his fever rose to 103 degrees Fahrenheit, which a staff member flagged with an exclamation point.

He reported abdominal pain, dizziness, headache, and decreased urination. He said he had recently been in Africa, but he denied being in contact with anyone sick, according to the AP. Doctors ordered a CT scan to rule out appendicitis, stroke, and other conditions. At the end of his initial visit, he was prescribed antibiotics and told to take Tylenol.

The hospital has said a communication breakdown led to the man's travel history not being factored into his care, and it expressed concerns that earlier isolation and treatment might have improved his prognosis and exposed fewer people to the virus.

In a statement today, the hospital's parent company, Texas Health Resources, said it continues to evaluate the events related to the man's Ebola infection and has made changes to some of its intake procedures and screening procedures for identifying Ebola infection. The facility said its staff is grieving Duncan's death and that it is willing to share the lessons they learned about Ebola treatment with other hospitals and medical teams.

In a related development, a Texas sheriff's deputy hospitalized for observation has been discharged from the same hospital in Dallas after lab tests were negative for Ebola, according to a statement yesterday from Texas Health Resources.

Ebola deaths climb above 4,000

In its latest update today the WHO said the global number of Ebola infections related to West Africa's outbreak as of Oct 8 has reached 8,399 cases, with the number of deaths rising to 4,033. The numbers reflect an increase of 366 cases and 168 deaths from the totals the WHO reported 2 days ago.

The numbers of illnesses and deaths reported from Guinea, Liberia, and Sierra Leone are thought to dramatically underestimate the true impact of the disease, and the WHO said this week that the situation in Liberia and Sierra Leone continues to deteriorate, especially in areas near the two capitals, an urban element that has been a unique feature of the current outbreak.

Liberia is still the hardest hit country for both illness and deaths. The WHO's update puts the illness total at 3,924 infections—roughly half of all of the outbreak cases—and the number of deaths at 2,210.

The WHO reiterated its assessment from earlier this week that data collection activities in Liberia aren't keeping up with illnesses and deaths and that so far there is no evidence that the outbreak is being brought under control.

Other developments

  • An official from the WHO said the group is finalizing legal paperwork to accept doses of experimental Ebola vaccine donated by Canada and that the vaccine will be shipped to Geneva next week, the Canadian Press reported today. The 800 to 1,000 vials of vaccine could provide as many as 100,000, depending on the results of dosing studies. Marie-Paule Kieny, MD, the WHO's assistant director general for health systems and innovations, told the Canadian Press that the vaccine was safely stored in Canada while clinical trials details were being settled and that the Geneva hospital that will store it needed to purchase a freezer to keep it at the proper temperature. The attenuated vesicular stomatitis virus (VSV) vaccine was developed by the Public Health Agency of Canada and is licensed by NewLink Genetics, based in Ames, Iowa.

  • The first Africa-based trial of another experimental Ebola vaccine launched on Oct 8 in Mali, targeting healthcare workers, according to a press release yesterday from the University of Maryland School of Medicine, which is partnering in the research. The vaccine is a chimpanzee-derived adenovirus vector (cAd3) vaccine developed by GlaxoSmithKline and the US National Institute of Allergy and Infectious Diseases (NIAID). Myron Levine, MD, director of the school's center for vaccine development, said in the statement that the study will yield crucial information on whether the vaccine is safe, well tolerated, and effective in the highest priority target group: healthcare workers. "If it works, in the foreseeable future it could help alter the dynamic of this epidemic by interrupting transmission to health care and other exposed front-line workers," he said.

  • Seven more contacts of the nurse in Spain who is being treated in isolation for an Ebola infection she contracted while caring for a missionary priest who was airlifted from West Africa's outbreak region have been admitted to a hospital for observation, Reuters reported today. The latest patients to be monitored include two hairdressers who had contact with the sick nurse before she was hospitalized and hospital staff who helped care for the nurse. So far, 14 people are in isolation and the nurse is reported to be in serious but stable condition, according to Reuters. Meanwhile, the European Centre for Disease Prevention and Control (ECDC) said today that as of yesterday, 58 contacts are being monitored, including 5 who are considered high-risk. It said the preliminary investigation suggests the cause of the woman's infection was an incident during the removal of protective gear on Sep 24.

See also:

Oct 10 Lancet letter

Oct 9 UN press release on World Bank Ebola meeting

Oct 10 World Bank press release

Oct 10 UN press release on General Assembly briefing

Oct 10 JAMA Intern Med Viewpoint abstract

Oct 10 AP story

Oct 10 Texas Hospital Resources statement on Duncan's case

Oct 9 Texas Hospital Resources statement on deputy's discharge

Oct 10 WHO Ebola roadmap situation update

Oct 10 Canadian Press story

Oct 9 University of Maryland School of Medicine press release

Oct 10 Reuters story

Oct 10 ECDC epidemiological update

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