title: Ledipasvir-Sofosbuvir for Treating Chronic Hepatitis C: A NICE Single Technology Appraisal-An Evidence Review Group Perspective.
abstract: The National Institute for Health and Care Excellence (NICE) invited Gilead, the company manufacturing ledipasvir-sofosbuvir (LDV/SOF), to submit evidence for the clinical effectiveness and cost effectiveness of LDV/SOF for treating chronic hepatitis C. The School of Health and Related Research (ScHARR) Technology Assessment Group was commissioned as the Evidence Review Group (ERG). This paper describes the company's submission (CS), the ERG review and the subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical effectiveness and cost-effectiveness evidence of LDV/SOF based upon the CS. The clinical effectiveness data for LDV/SOF were taken from ten trials: three phase III trials and seven phase II trials. Trials compared different durations of LDV/SOF, with and without ribavirin (RBV). There were no head-to-head trials comparing LDV/SOF with any comparator listed in the NICE scope. Data from the trials were mostly from populations with genotype 1 (GT1) disease, although some limited data were available for populations with genotypes 3 and 4. For GT1 treatment-naïve patients, sustained viral response for 12 weeks (SVR12) rates for LDV/SOF ranged from 93.1 to 99.4 % for subgroups of patients with non-cirrhotic disease, whilst SVR rates of 94.1 to 100 % were reported for subgroups of patients with compensated cirrhosis. For GT1 treatment-experienced patients, SVR12 rates ranging from 95.4 to 100 % were reported for subgroups of non-cirrhotic patients, and SVR rates ranging from 81.8 to 100 % were reported within subgroups of patients with compensated cirrhosis. Comparator data were not searched systematically as part of the submission, but were based on the company's previous NICE submission of sofosbuvir, with additional targeted searches. The ERG's critical appraisal of the company's economic evaluation highlighted a number of concerns. The ERG's base case analyses suggested that the incremental cost-effectiveness ratios (ICERs) for LDV/SOF (+RBV) are dependent on (a) treatment durations, (b) whether patients have been previously treated and (c) whether patients have liver cirrhosis or not. The AC concluded that it was appropriate to use the approach taken in the ERG's exploratory analyses, in line with the marketing authorisation, which considered people with and without cirrhosis separately, and estimated the cost effectiveness for each recommended treatment duration of LDV/SOF.
authors.affiliation: University of Sheffield, Sheffield, UK. p.thokala@sheffield.ac.uk.
authors.forename: P
authors.identifier: 0000-0003-4122-2366
authors.initials: P
authors.lastname: Thokala
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: E L
authors.initials: EL
authors.lastname: Simpson
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: P
authors.initials: P
authors.lastname: Tappenden
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: J W
authors.initials: JW
authors.lastname: Stevens
authors.affiliation: University of Sheffield, Sheffield, UK.
authors.forename: K
authors.initials: K
authors.lastname: Dickinson
authors.affiliation: Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, UK.
authors.forename: S
authors.initials: S
authors.lastname: Ryder
authors.affiliation: King's College Hospital, Denmark Hill, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Harrison
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000191:economics; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000191:economics; D003362:Cost-Benefit Analysis; D005449:Fluorenes / Q000008:administration & dosage* / Q000191:economics; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000191:economics / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000191:economics / Q000821:virology; D000069474:Sofosbuvir; D013997:Time Factors; D014542:Uridine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000191:economics
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D005449:Fluorenes; C000595958:ledipasvir, sofosbuvir drug combination; D014542:Uridine Monophosphate; D000069474:Sofosbuvir