Since the mid-1980s, ribavirin has been a key drug in treating Lassa fever worldwide. However, its widespread use and “unequivocal recommendation” in national guidelines has been underpinned by an unsound study. New research suggests that a series of past studies into its effectiveness in cutting death rates were at critical risk of bias. The authors have called for high-quality randomised trials to be carried out on ribavirin as a matter of urgency.
Lassa fever, which is mainly found in West Africa, is seen as a priority disease by the WHO (World Health Organization). There are up to 200,000 cases a year, mortality rates are high (10% to 20% in hospitalised cases) and epidemic potential is also high. There is no available vaccine and treatments, other than ribavirin, are very limited.
In recent years concern has grown about the quality of evidence for ribavirin’s effectiveness. The research team’s challenge was to gather and assess past research, including the largest ever study, carried out by the US military but never published.
Freedom of Information legislation was used to gain access to the US military research, which was conducted in Sierra Leone. The team firstly re-analysed and assessed the unpublished data (Time to reconsider the role of ribavirin in Lassa fever, PLOS Neglected Tropical Diseases Journal, July 2021). This was then subjected to state-of-the-art techniques (applying the Robbins-I tool and a systematic review approach) for identifying 12 other studies (described in 15 papers) and assessing risk of bias to evaluate the effectiveness of ribavirin in Lassa fever.
The resulting paper Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies (published in EID (Emerging Infectious Disease) Journal, August 2022) found all but one study to be at serious risk of bias, and the other at critical risk. Which overthrew the favourable results to ribavirin in the included studies.
As a result the team, which includes HDR UK affiliated researcher Professor Jonathan Sterne, concluded that existing research into the use of ribavirin for Lassa fever should be re-evaluated.
The team believes their research has important implications for clinical practice and research and their findings are already having a positive impact.
The paper’s lead author Dr Hung-Yuan (Vincent) Cheng, a University of Bristol Medical School researcher, said: “The work has now been presented in WHO meetings and it is changing their way of thinking about the evidence. They are now planning to establish well-designed trials.”
The team also believes that data-based research should be not simply driven by the results and more time focus should be placed on context and appraisals.
What the Impact Committee said:
The committee praised the work for its potential to affect public health and healthcare decision making and economics.
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