Over the past three years, high-profile outbreaks of Ebola and the Zika Virus have stimulated an unprecedented level of interest in developing vaccines to prevent these two viral infections.
Public health advocates and pharmaceutical companies are working together to advance promising leads into human studies. However, both of these diseases disappeared rapidly, which makes evaluating their effectiveness using traditional randomised controlled trials (RCT) difficult.
The 2014 Ebola outbreak killed thousands of people in West Africa and stoked the fears of a global epidemic. This led to an intense competition to develop the world’s first Ebola vaccine, with Merck & Co, GlaxoSmithKline (GSK), and Johnson & Johnson (J&J) headlining a long list of companies.
Despite the rapid progression of several vaccines through early-stage human studies, with Merck and NewLink Genetics’ rVSV-ZEBOV-GP in an ongoing Phase III safety / immunogenicity trial, clinical research has slowed due to the outbreak’s conclusion. While recently reported cases of Ebola in Congo may provide an opportunity for rVSV-ZEBOV-GP to prove its worth in a real-world setting, stakeholders must accept the reality that large RCTs demonstrating clinically significant efficacy aren’t feasible, for both epidemiological and ethical reasons.
In the case of the Zika Virus, an apparent link between the infection and severe birth defects, most notably a 2016 spike in cases of microcephaly (abnormally small head) associated with Zika infections in Brazil, led to a surge in epidemiological and vaccine research activity. However, so far in 2017, the incidence of Zika has plummeted, threatening to derail large-scale studies commissioned to investigate this pattern of birth defects known as congenital Zika syndrome. Vaccine developers are being similarly impacted by the decrease in Zika cases.
While recent Ebola and Zika outbreaks have presented both epidemiologists and vaccine developers with challenges, they represent valuable case studies in how researchers can alter their approaches to achieve meaningful results. For example, stakeholders have learned that rapid standardisation of study endpoints and trial design is essential, as it allows multiple trials enrolling fewer participants to pool and / or directly compare their data in the event they must be cut short due to a rescinding outbreak.
In the case of vaccine research and development (R&D) specifically, Merck’s rVSV-ZEBOV-GP was demonstrated to be safe in healthy individuals and is now being stockpiled for a future Ebola outbreak, despite limited evidence of the strength and duration of its protective efficacy. To achieve results in an ethical manner, the bar must be set lower than the RCT.