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General News of Sunday, 5 July 2015

Source: Public Agenda

Doubts over integrity of Ebola trials

Though the public outcry over attempts by health authorities in Ghana to try out an Ebola Virus Disease (EVD) vaccine trial in the Volta Region appears to have subsided, Ghanaians are yet to receive official responses to some of the critical questions raised in the midst of those anxious moments.

Though a bit late in joining the public discourse on the proposed clinical trials, the country's foremost assembly of academics and scientists, the Ghana Academy of Arts and Sciences' statement issued provides enough scientific basis for questioning the motive of Ghanaian authorities for opting to be part of the trials taking place in other parts of the sub-region, particularly the Ebola-endemic areas.

The report of a 5-member Technical Committee set up by the Academy to investigate issues around the proposed trials raised fundamental questions that must be addressed before a final decision is taken on whether or not to proceed with the trials. Addressing these questions do not only help to address current public concerns about the trials, but also serve as a useful guide on how to approach a similar issue in future.

The main concerns raised by the Technical Committee of the Academy relate to the following:

1. Uncertainties about the appropriateness of the vaccine, including:

a. The nature and origins of the Ebola virus, including the circumstances of its appearance in Guinea;

b. Whether the Zaire strain of the virus, which is the one being used in the GSK vaccine to be tested in Ghana, is the strain responsible for the Ebola epidemics in Liberia, Mali, Nigeria, Senegal and Sierra Leone, and

c. The identity and characteristics of other strains of the Ebola virus that might exist;

2. The use in the GSK/NIH vaccine of a gene particle of the wild species of the Zaire Ebola virus, rather than the gene particle of the Makona strain isolated in the epidemic in Guinea;

3. What pre-clinical animal experimentations had been carried out with a vaccine based on the Makona strain to establish evidence of safety, immunogenicity and protection;

4. What basis is there for expecting that immune responses generated against the wild type Zaire Ebola virus GSK vaccine formulation (construct), with a live non-replicating chimpanzee adenovirus carrying a gene from Zaire Ebola virus, would be effective against the Makona strain or any other Ebola virus species and strains;

5. After a test vaccine has been shown in the vaccinated individual to produce an immune response (immunogenicity), what guarantee would there be, in this instance, that the vaccine would offer protection against the full Zaire Ebola virus and other species and strains;

6. On the basis of research conducted so far towards vaccine development, what is the likelihood of the present construct of vaccines protecting communities against the rapid emergence of new, more virulent strains of the virus, as appears to have happened with the Makona: the risk of false confidence deriving from the use of a new vaccine must be noted;

7. What assurances do we have that the chimpanzee-derived live adenovirus vector used in the GSK vaccine construct, although non-replicating for now, will remain dormant and not itself cause a disease to compromise the health of the people of Ghana;

8. It is to be noted that the application for the GSK Ebola vaccine Phase II trial in Ghana includes children, even though the Phase I trial in the US, UK, Mali and Switzerland was limited to adults, raising the question of dosage profiles for children and other vulnerable groups in the Phase II trial;

9.What evidence is there of strict compliance with the International Committee on Harmonization Protocol Guidelines for Clinical Trials, including full “informed consent” by all volunteers?

The Ghana Academy of Arts and Sciences says, in discharge of its mandate to provide independent science-based advice for policy making, its Council asked the President of the Academy to bring these concerns urgently to the attention of the Minister for Health.

This, the Academy says was immediate, attaching a copy of the preliminary report of the Committee and confirming the Academy's preparedness to provide all necessary support to the Ministry in dealing with the matter.

The Academy says after some delay, the newly-appointed Minister of Health convened a meeting on June 03, at which the concerns and issues it had raised were discussed with the technical staff of the Ministry of Health (MOH), the Food and Drugs Authority and its expert advisors, as well as the Principal Investigators in the GSK/NIH Phase II trials.

The meeting, according to the Academy's statement confirmed that the processes for the approval of the Phase II clinical trial of the GSK Ebola Virus Disease test vaccine had not been concluded.

The statement said the Academy was shocked to discover that approval had already been given to an application for a separate Phase I trial in Hohoe, of a test vaccine with a different construct from the GSK test vaccine, as nothing had been said anywhere previously about a separate Phase I clinical trial application, let alone its approval.

The Academy notes that, the Phase I trial of the GSK vaccine in Europe produced adverse results, particularly, prolonged bleeding in 10% - 15% of the vaccinated population. This it says is a serious adverse development that calls for extreme caution in approving clinical trials, both Phase I and Phase II, in the country.

Moreover, the statement argues, “it is the case that those vaccinated at Phase I and Phase II may be shedding the adenovirus vector into the surrounding community. In the absence of a map of adenovirus prevalence in the trial sites, there is a high risk of an 'escape virus' merging with the endemic adenoviruses to create more virulent strains.”

For that reason alone, the statement points out, “it is important that the exposed communities and, indeed, the general public be adequately informed of such trials and their benefits and risks”.

The conclusion of the country's august body of academics and scientists is that, subject to satisfactory answers to the issues it has raised, and considering the gaps in our knowledge and state of preparedness, it would be unsafe to undertake the proposed EVD vaccine clinical trials in Ghana.