Comparing direct acting antivirals for hepatitis C using observational data - Why and how?

Area of Science:

• Hepatology
• Pharmacoeconomics
• Clinical Trial Emulation

Background:

• The World Health Organization aims for hepatitis C virus (HCV) elimination by 2030, necessitating affordable treatments.
• Direct-acting antivirals (DAAs) are crucial, but many are approved without comparative efficacy data.
• This study addresses the comparative effectiveness of two DAAs for genotype 1 HCV.

Purpose of the Study:

• To emulate a randomized trial comparing sofosbuvir/ledipasvir (SOF/LDV) versus sofosbuvir/velpatasvir (SOF/VEL) in genotype 1 HCV patients.
• To determine if SOF/LDV is non-inferior to SOF/VEL in treating HCV.
• To provide a template for drug comparison in the absence of direct comparative trials.

Main Methods:

• Emulated a randomized trial using propensity score matching on the British Columbia Hepatitis Testers Cohort.
• Included patients with genotype 1 HCV and no comorbidities or end-stage liver disease.
• Employed a Bayesian logistic model with random effects to estimate treatment failure risk difference.

Main Results:

• Treatment success rates were 97% for SOF/VEL and 95% for SOF/LDV.
• The estimated risk difference was 2% (95% CrI 0%-4%), indicating non-inferiority.
• Treatment failure occurred in 3% of SOF/VEL patients and 5% of SOF/LDV patients.

Conclusions:

• Sofosbuvir/ledipasvir (SOF/LDV) is non-inferior to sofosbuvir/velpatasvir (SOF/VEL) for treating genotype 1 HCV in easily treated patients.
• This trial emulation method provides a viable approach for comparing drug efficacy when direct comparative trials are unavailable.
• Findings support informed treatment decisions and potentially lower drug costs for HCV elimination efforts.