CMAJ News WHO enters new terrain in Ebola research he meeting on unproven inter- ventions for Ebola at the World T Health Organization on Sept. 4 and 5 takes the global agency into “absolutely uncharted territory,” says WHO spokesperson, Dr. Margaret Harris. “We’re actually often criticized for being incredibly slow about saying, ‘Do this over that’, because we demand enormous levels of evidence,” she says. But for Ebola virus disease, there are no approved therapies, so WHO is attempting to move investigational interventions forward, including medi- cations, vaccines and so-called conva- lescent serum, made from the blood of survivors. The Sept. 4 meeting, aimed at guid- ing research in the midst of the out- NikiLitov/iStock/Thinkstock break, marks a sharp turn for WHO, In the absence of approved therapies for patients diagnosed with Ebola, WHO is taking where research efforts are viewed as the unprecedented step of attempting to move research forward. fragmented. About five years ago, WHO eliminated its office of research break at 78%, and in late August the three control animals died. Five of the strategy; the department leading the disease spread to another country — seven people treated with ZMapp have Ebola research effort, known as Senegal — and another city — Port survived, but it is unclear if the medica- Knowledge, Ethics and Research, was Harcourt, Nigeria, the hub of Nigeria’s tion helped them to recover and it will only formed at the end of 2013. But the oil and gas industry, where Canadian be months before there is more ZMapp Ebola crisis forced a change. Says Har- oil executives travel regularly. available. ris, “We’re in a desperate situation, In this urgent context, hundreds of PHAC is also represented by Dr. where people are dying in numbers that scientists, company representatives, eth- Tom Wong, director, Influenza and are far too high and there is no specific icists and drug regulatory officials from other Respiratory Infectious Disease treatment to offer them.” Health Canada, the FDA and Europe’s Division, and Dr. Theresa Tam, branch In August, WHO convened an ad EMEA along with representatives from head, Health Security Infrastructure hoc ethics panel to advise on the use of nongovernmental organizations, and Branch. Dr. Lindsay Elmgren, director, investigational drugs — such as the health officials and community leaders Centre of Biologics Evaluation is experimental cocktail of monoclonal from areas affected by Ebola, are in attending on behalf of Health Canada. antibodies known as ZMapp, which has Geneva to consider “what’s viable and The University of Toronto’s Dr. been given to seven patients. The panel what’s not, what’s feasible and what’s Eleanor Fish, who may also present concluded that given the circumstances not,” Harris says. Sept. 4, advocates treating Ebola patients it is ethical to offer unregistered drugs, Technical presentations are slated for with a form of interferon alpha, a treat- but the drugs must be evaluated “in the Sept. 4. Dr. Gary Kobinger of the Public ment that was beneficial when used best possible clinical trials under the Health Agency of Canada (PHAC) and to treat patients with SARS at Toron- circumstances” and there is a moral the National Microbiology Laboratory to’s North York General Hospital dur- obligation to “collect and share all data in Winnipeg will attend and may ing the 2003 outbreak. In an email to generated.” describe the preclinical work his team CMAJ, Fish said that that she believes In the weeks since then, the crisis published in Nature Aug. 29, showing interferon should be “seriously consid- has worsened. WHO now says that the that ZMapp is effective in primates. The ered” for use soon after a person has caseload of those infected “could Canadian team infected 21 monkeys been exposed to Ebola because it could exceed 20 000 over the course of this with Ebola virus and gave 18 of the ani- possibly reduce viremia, allowing sup- emergency”; scientists put the case mals ZMapp at different times. The portive care and other therapies to be fatality rate of the current Ebola out- treated monkeys all lived while the more effective. © 2014 Canadian Medical Association or its licensors CMAJ, October 7, 2014, 186(14) E527 News Although Fish hopes “there will be a Ebola patients is worrisome. Given how ing, as it is terra incognito and the out- consensus to move forward with a pilot demanding trials are, Lavery fears that break is out of control.” evaluation” of interferon, Thomas “the proper focus on public health and The lack of research on how to treat Geisbert, an Ebola expert at the Univer- clinical issues could easily be overrun Ebola has already captured the atten- sity of Texas Medical Branch in by a lot of the real nuances that have to tion of research funders. On Aug. 21, Galveston, is critical of the idea. In an be managed at research sites.” the London-based Wellcome Trust and e-mail to CMAJ, he said that when These sorts of dilemma will be dis- the UK’s Department for International tested in monkeys, some interferons cussed at a session devoted to develop- Development announced a joint request “actually made things worse where the ment of an ethics framework, where the for Ebola research proposals, placing treated animals died faster than the WHO’s ethics advisory panel will pres- 6.5 million British pounds on the table untreated controls.” His preference is to ent a more thorough guidance docu- with an application deadline of Sept. 8. test the therapies “proven to be the ment including contributions by panel Upshur suspects that a consortium, pos- most effective in nonhuman primates,” member and University of Toronto sibly involving these sponsors, will be such as ZMapp. public health researcher, Dr. Ross formed to provide overall leadership Yet for some observers, including Upshur. Upshur, a highly sought expert for the Ebola research initiative. — Jim Lavery, a global research expert at on the ethical issues that arise during Miriam Shuchman, Toronto, Ont. St. Michael’s Hospital in Toronto, doing pandemics, told CMAJ by email that any clinical trial in a hospital treating he’s found his work on Ebola “exhaust- CMAJ 2014. DOI:10.1503/cmaj.109-4893 E528 CMAJ, October 7, 2014, 186(14) .