Conventional Wisdom versus Actual Outcomes: Challenges in the Conduct of an Ebola Vaccine Trial in Liberia during the International Public Health Emergency

Abstract

Abstract.Clinical trials are challenging endeavors. Planning and implementing an investigational vaccine trial in Liberia, in the midst of an Ebola virus disease (EVD) epidemic that World Health Organization classified a public health emergency of international concern, presented extraordinary challenges. Normally, years of preparation and a litany of tasks lay the groundwork for a successful, randomized, blinded, placebo-controlled trial focused on safety and efficacy. Difficult research settings, unpredictable events, and other unique circumstances can add complexity. The setting in Liberia was especially problematic due to an infrastructure still badly damaged following a lengthy civil war and a very fragile health-care system that was further devastated by the EVD outbreak. The Partnership for Research on Vaccines in Liberia I EVD vaccine trial was planned and implemented in less than 3 months by a Liberian and U.S. research partnership, and its Phase II substudy was fully enrolled 3 months later. Contrasting conventional wisdom with trial outcomes offers an opportunity to compare early assumptions, barriers encountered, and adaptive strategies used, with end results. Understanding what was learned can inform future trial responses when disease outbreaks, especially in resource-poor locations with minimal infrastructure, pose a significant threat to public health.

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review

“…International research collaborations should be tied to capacity building and be genuinely collaborative [22], with local stakeholders engaged from inception [1, 3, 13, 16-19, 22, 26, 29, 31, 32, 36, 38, 40, 44, 50, 51]. Support from national governments and local communities was a key enabler [16,17,23,32,36]. Continuous dialogue, led by governments of affected nations [16, Table 1 The search strategy for Scopus and Epistemonikos (zika* OR zikv* OR ebola* OR "middle east respiratory syndrome*" OR "MERS-CoV" OR h7n9 OR h1n1 OR h5n1 OR nipah OR cholera* OR "yellow fever" OR influenza OR ((outbreak* OR pandemic* OR epidemic*) AND ("infectious disease*" OR "communicable disease*"))) AND (research OR "clinical trial*" OR "vaccin* trial*") AND (politic* OR economic* OR administrat* OR regulat* OR logistic* OR ethic* OR social* OR cultur* OR behavior* OR behaviour*) AND (barrier* OR bottleneck* OR delay* OR "time delay*" OR expedite* OR solution* OR facilitate*).…”

EBOVAC-Salone: Lessons learned from implementing an Ebola vaccine trial in an Ebola-affected country

“…Contrary to the experience of some groups conducting research during the outbreak, generous financial compensation was not necessary to stimulate participation in the trial in Kambia. 8 Study partners sought advice from the national ethics committee before agreeing to rates that would fairly recompense a participant’s time and transport without providing undue inducement, based on estimated lost earnings and transport costs to and from the clinic.…”

“… 5 The challenges were not just for researchers: the burden on local ethics committees, dealing with huge increases in workload, was also noted. 7 – 9 …”

Development of a TB vaccine trial site in Africa and lessons from the Ebola experience.

“…Preliminary e cacy results were availed in unprecedented time for rapid decision making (17). The transition to Phase II/III studies was unmatched, at eight months, instead of ordinarily one to three years (18,19) after initiation of the phase I study (2).…”

“…Thus, local trained research teams were virtually non-existent (21), as were any 'clinical research sites' (16,21). Despite all this, the necessary facilities were put up on the go, and teams adapted other trial aspects to the less ideal realities in the eld (19).…”