WHO’s Comprehensive Plan to Rapidly Develop Therapeutics and Vaccines
Despite research into Ebola vaccines and therapeutics over the past decade, no product has been fully evaluated and approved for human use. This means that the only way to deal with this unprecedented outbreak has been to use the same basic public health and supportive care measures that were available in the past. Having an effective vaccine could have stopped the spread of the epidemic in it’s tracks and help prevent future outbreaks, while the development and availability of safe and effective therapeutics could have improved survival and sped patients’ recovery.
While this outbreak continues, there is both a critical need and an unprecedented opportunity to evaluate vaccines and therapies for Ebola.
On the phone from Geneva, Dr. Cathy Roth of the World Health Organization (WHO) told the audience of a special symposia on Ebola at the 2014 American Society of Tropical Medicine and Hygiene meeting held in New Orleans, about WHO’s comprehensive plan to develop new therapeutics and vaccines at an unprecedented speed.
“In parallel with the massive Ebola response and within the context of the provision of care, we are proceeding to accelerate to the evaluation and eventual access to vaccines and therapeutics —and we are intending to do this in a time-scale which is very compressed. Taking such interventions from development phases into human use can take years—up to ten years. We are attempting to do this in as many months without sacrificing safety and our understanding of the efficacy of these treatments,” Dr Roth said.
These plans have been developed over the course of several consultations convened in Geneva.
The first meeting held on August 11 2014, involved a panel of ethicists and other epidemiologists and regulators who concluded that it would be ethical, in the current Ebola outbreak context, to offer unapproved interventions as potential treatment or prevention “as long as certain ethical, scientific and practical criteria were met,” according to the report from the meeting.
At a second much larger consultation on potential Ebola vaccines and therapies, with a range of stakeholders and national representatives, it was decided that:
- As a matter of priority, the use of whole-blood transfusion and convalescent plasma should be studied as soon as possible.
- Two candidate Ebola vaccines, the vesicular stomatitis virus (rVSV-ZEBOV) and chimpanzee adenovirus (ChAD3-ZEBOV) were ready and were prioritized for human studies immediately.
- There was adequate evidence supporting the further evaluation of certain selected novel therapeutics on the basis of studies in non-human primates and other scientific data, (see related articles).
A third consultation on study designs for Ebola vaccines, concluded that although well-designed randomized controlled trials would generate the most reliable and robust data regarding vaccine efficacy if it was not possible to proceed with randomized controlled trials of vaccines (due to fear or other situations in the affected countries), there are reasonable alternatives such as studies using ‘step-wedge’ designs (see related article).
Although some media reports have suggested that WHO believes randomized placebo controlled trials for Ebola are unethical, the positions that came out of the consultations are more nuanced, and readers are referred to the reports produced by those meetings. For instance, Dr. Roth stressed that supplies of all the new agents are limited and in some cases exhausted, and there will be challenges to implementing any study in these settings.
“One of the bases for any of these studies is that the background for any potential evaluation must include an adequate standard of supportive care,” said Dr. Roth. It should be noted however that this standard is not yet widely achieved within the epidemic settings — but where it has been, there has been a significant decline in mortality.
Dr. Roth also stressed that the number of sites where clinical trials of any sort can be undertaken is very limited, and that it is essential that research into Ebola vaccines and therapeutics must not interfere with the delivery of the basic care delivered to the patients in the centers.
“We recognize that the number of healthcare workers is extremely limited and we must also make sure that they can do their basic work in safety and not have these clinical studies in any way distract from their safety or what is provided for the population in terms of care,” she said.
Moving ahead with trials and readiness preparation simultaneously
If things go well and according to plan, an effective vaccine could be identified as soon as the end of the first quarter of 2015. But in parallel with the acquisition of efficacy data, planning for large-scale use, including systems for vaccine financing, allocation, and use will be necessary.
WHO has developed a comprehensive plan that focused both on what must be done to evaluate the products today and what must begin very soon for the future so that if either of these vaccines does demonstrate utility it can be very rapidly deployed in the best possible way and reliably potential supply.
The regulation and safety issues are clearly paramount. While the ASTMH conference was ongoing, in Pretoria, South Africa, the African Regulators Network was meeting to discuss collaborative mechanisms for the fast-tracking approvals for clinical trials and for registration so that if any product is found to have an impact in these studies, access in the affected countries and their surrounding countries can be harmonized.
There will be issues around supply and demand:
- How can we ensure that the formulations available are suited to use to the conditions in which they will be used as is possible?
- What are the strategies for access?
- What are the different scenarios?
- What is the recommended use for the initial vaccine stocks when the supplies are limited?
- How should the cold-chain be managed and scaled up? (Refrigeration in shipping and storage affect the stability of some products, and are a challenge in a resourced-constrained tropical setting)
- What are the main drivers of cost and how can they be managed?
- What are the enablers?
- How can this be financed?
- How can procurement be organized?
- What are the issues around coordination and alignment of having multiple partners?
- What are the issues about liability?
Dr. Roth said that another high-level meeting was convened in the previous week by WHO with representatives from governments, manufacturers, scientists, and the partners who will be trialing these vaccines in order to coordinate these issues.
One decision reached was that healthcare workers including medical staff, laboratory staff, burial teams, and cleaners in the health facilities should have first call on vaccine doses while supplies remain limited. The vaccination of healthcare workers – should an effective vaccine emerge — could even move forward after the first quarter of 2015.
Finally, “there is a determination to finish the job. All of these efforts to test and approve Ebola vaccines — and this goes for therapeutics as well — must be followed through to completion at the current accelerated pace. Even if the dramatic changes in the epidemic’s transmission dynamics meant that they were no longer needed for this one, that for future outbreaks, we must never again find ourselves unprepared,” Dr. Roth concluded.
Global Health Strategies generously supported Theo Smart’s attendance at the 63rd Annual American Society of Tropical Medicine and Hygiene Conference in New Orleans.