The World Health Organization (WHO) said today that its advisory committee on experimental Ebola drugs, which met this week, leaned toward doing randomized controlled trials, an approach that has drawn objections from some experts because it involves withholding experimental drugs from control group members.
The WHO also reported that clinical trials of the use of whole blood and blood plasma from Ebola survivors are ready to start in two countries.
The WHO's Scientific and Technical Advisory Committee for Ebola Experimental Interventions (STAC-EE) met in Geneva Nov 11 and 12, the WHO said in a statement. The sessions included experts on the Ebola virus and preclinical and clinical testing, pharmacologists, sociologists, public health experts, regulators, and officials from countries in West Africa.
The panel reviewed the effects of some experimental products on 18 patients who were evacuated from West Africa to "well-resourced facilities" in other countries, the agency said. "Resulting data did not permit evaluation of efficacy of these interventions, and the comparatively high survival rate observed in these patients may be due to a variety of factors including the high standard of care they received," it stated.
A proposal a day
The WHO said it and its partners receive "daily proposals" for potential Ebola treatments, with a number far exceeding possible sites for testing them. Hence the panel developed a set of criteria concerning minimal preclinical and clinical results that should be achieved for a product to be considered for inclusion in clinical trials. The criteria will be published on the WHO Web site.
The agency cited two general categories of proposed Ebola drugs: certain experimental ones that have shown good results in animals but are in early development and very limited supply, and drugs that are easier to make or are already in use for other purposes but have shown limited activity against Ebola in lab culture or animal studies. The latter category includes favipiravir, brincidofivir, toremifine, and interferons.
The committee reviewed clinical trial protocols that various groups presented for these four drugs, the WHO said. They found two basic trial designs: (1) a historically controlled—meaning non-randomized—trial that, depending on results, could lead to a subsequent randomized trial and (2) a randomized, concurrently controlled trial that would start with a control arm that would get the best available supportive care, with the intent to add an effective Ebola treatment for the control group as soon as one is identified.
The feasibility of the two approaches and the expected data quality "were vigorously debated, and it was generally conceded that each method had pros and cons for given situations, but that it was likely that for anti-Ebola treatments that did not have large effects, randomized concurrently controlled trials may be needed," the WHO reported.
The statement also said one antiretroviral drug, lamivudine, has been used in some of the Ebola-affected countries in the belief that it might provide some benefit. "However, data presented to the STAC-EE demonstrated that lamivudine has no antiviral activity against EVD [Ebola virus disease] and should therefore not be administered for the treatment of Ebola."
Blood-product trials planned
As for using blood and blood products, the committee was told that a study soon to start in Guinea will first evaluate convalescent whole blood (CWB) and then switch to convalescent plasma (CP) once supplies become available, the WHO said. The trial is being organized by a consortium from Belgium, France, Guinea, and the United Kingdom.
Another study soon to begin in Guinea will evaluate CP only, the statement said, adding, "Studies being planned in Sierra Leone will evaluate CP, but also make provision for use of CWB under compassionate use."
The panel also called for further investigation of the option of making immunoglobulin (IG) from survivors, as it may have advantages over CWB or CP as a public health intervention, the agency reported. Because the affected countries don't have blood fractionation facilities, it will be necessary to consider using facilities in other countries to pursue this option, it said.
IOM calls for wide-ranging research
In related developments, an Institute of Medicine (IOM) Ebola workshop last week focused on the need for research in many areas, including transmission risks, exposure routes, personal protective equipment (PPE), waste management, emergency preparedness, and the need to conduct research now, while the epidemic still roils, according to a workshop report published today.
Pressing transmission issues included whether subclinical transmission exists, the viral load during different EVD phases, household transmission, the potential for aerosol spread, and intermediate hosts and vectors, the report said. PPE topics included optimizing the supply chain, testing equipment performance, PPE design, and training needs of health workers.
Nov 14 WHO statement on Ebola treatments
Nov 14 IOM report