Cost-effectiveness of community-based repurposed therapies for COVID-19 in the PRINCIPLE trial

During the early phases of the COVID-19 pandemic, health systems faced urgent decisions about allocating resources to repurposed community treatments in the absence of definitive evidence. While large platform trials reported clinical outcomes, their implications for cost-effective resource allocation under uncertainty remain unclear. Using the Platform Randomised trIal of treatmeNts in the Community for epIdemic and Pandemic iLlnEsses (PRINCIPLE) trial as a case study, we evaluated the cost-effectiveness of six repurposed drugs compared with usual care.

Trial-based economic analyses assessed National Health Service (NHS) costs and clinical outcomes over 28 days post-randomisation using multiply imputed data. Incremental cost-effectiveness ratios (ICERs) were estimated as incremental cost per day saved until recovery and per hospitalisation or death avoided. Sensitivity analyses explored decision uncertainty.

A total of 8825 participants randomised between April 3, 2020 and July 1, 2022 were included. Inhaled budesonide showed a favourable balance across outcomes, with ICERs of £6,386 per hospitalisation or death avoided and -£77 per day saved until recovery, indicating lower costs and faster recovery than usual care. Colchicine had a low ICER for hospitalisation or death avoided (£2,858), but limited recovery benefit. Azithromycin and doxycycline were cost-saving for recovery but had high ICERs for hospitalisation or death avoided (£27,490 and £21,278, respectively). Favipiravir was associated with lower costs and faster recovery but higher cost for a modest reduction in hospitalisation or death avoided than usual care. Ivermectin was associated with higher costs for both outcomes and had a low probability of cost-effectiveness. Sensitivity analyses largely supported these findings.

Trial-based economic evidence from large platform trials can inform efficient resource allocation during public health emergencies, including identifying interventions that offer limited or no economic value. These findings highlight the importance of integrating economic evaluation into rapid trial platforms to support timely funding and disinvestment decisions under uncertainty.

ISRCTN registry, ISRCTN86534580, registered 23 March 2020.