A standardised Phase III clinical trial framework to assess therapeutic interventions for Lassa fever

PLoS Negl Trop Dis. 2022 Jan 6;16(1):e0010089. doi: 10.1371/journal.pntd.0010089. eCollection 2022 Jan.

Abstract

Background: Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence.

Methodology: We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology.

Results: A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols.

Conclusions: This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.

MeSH terms

  • Antiviral Agents / pharmacology*
  • Clinical Trials, Phase III as Topic / methods*
  • Drug Development / methods*
  • Drug Discovery / methods
  • Humans
  • Lassa Fever / drug therapy*
  • Lassa virus / drug effects
  • Research Design
  • Surveys and Questionnaires

Substances

  • Antiviral Agents