Economic analysis to support NHS implementation of hepatitis c drugs: prioritisation of the treatment options for patients with chronic hepatitis c at the METAVIR f3 stage

A number of new treatments for infection by hepatitis C virus (HCV) have recently undergone or are currently undergoing appraisal by the National Institute for Health and Care Excellence (NICE). The objective of these appraisals was to assess their value to the National Health Service (NHS) in England and Wales. These treatments are: simeprevir (SMV), sofosbuvir (SOF), ledipasvir-sofosbuvir (SOF+LED), daclatasvir (DCV) and ombitasvir-paritaprevir-ritonavir with or without dasabuvir (2D/3D). These new treatments provide an alternative to the existing interferon-based therapies: dual therapy with peginterferon and ribavirin (PR), and triple therapy with a protease inhibitor (boceprevir or telaprevir) in combination with PR.

The NICE guidance has considered whether each new drug might provide value for patients at a particular disease and treatment stage. However, there is no clear guidance on how to prioritise implementation of the range of treatments now recommended as options by NICE in a way that maximises health benefits and value to the NHS.

1.2 Aims and objectives

The aim of this work is to inform NHS policy for the use of direct-acting antivirals in the treatment of patients with chronic hepatitis C in patients at high risk of progression to cirrhosis, those with METAVIR F3 liver fibrosis.

This work extends previous cost-effectiveness analyses of these interventions in three important ways:

i. It compares all the new treatments head-to-head.

ii. It allows for re-treatment of treatment failures at the F3 stage, thereby comparing each treatment as first, second or third line therapy.

iii. It includes the possibility of (re-)treatment at the stages of cirrhosis and decompensated cirrhosis.

The specific objectives are to examine whether patients should be treated at the F3 stage, to assess how many lines of treatment and which treatments patients should receive, to evaluate their budget impact and to identify the key areas of uncertainty for which more research is required.

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1.3 Methods

1.3.1 Prioritisation analysis

The cost-effectiveness of the different treatment strategies was evaluated by comparing their costs and health benefits over a lifetime horizon using a decision-analytic model. Health benefits are expressed in quality-adjusted life years (QALYs). Costs are in UK pound sterling at a 2014 price base from the perspective of the UK NHS. The patient population comprises all patients with chronic hepatitis C who are considered to have progressed to METAVIR stage F3. The patient population is stratified into subgroups defined by genotype, interferon eligibility and prior treatment experience with peginterferon or protease inhibitor-based therapy. Patients with cirrhosis and decompensated cirrhosis are offered treatment through NHS England’s commissioning policy. The treatment strategies evaluated include all possible permutations of the available treatments in up to three lines of treatment in addition to watchful waiting followed by treatment at the cirrhosis stage. The model inputs were obtained from the NICE appraisals of the new treatments, as these appraisals incorporate a systematic review and endeavour to summarise the best available evidence. Treatment costs are based on publicly available list prices.

1.3.2 Budget impact

The budget impact analysis calculates the total and annual NHS expenditure over 10 years associated with treating patients at the METAVIR F3 stage with the strategy found to be cost-effective in the prioritisation analysis. For illustration, these costs are compared with the expenditure associated with offering patients PR or no treatment until progression to cirrhosis to provide an indication of incremental budget impact. The costs considered are treatment costs at METAVIR F3, treatment costs at cirrhosis and decompensated cirrhosis and costs associated with monitoring and complications from the disease. The cost inputs are obtained from the cost-effectiveness model. The number of F3 patients was based on the estimates used in the NICE appraisals (16,819 patients; 3% patients treated per year). Half of the newly progressed patients to METAVIR F3 are assumed to be treated.

1.4 Results

1.4.1 Prioritisation analysis

The table below presents the cost-effective strategies at £20,000, £25,000 and £30,000 per QALY cost-effectiveness thresholds (hereafter referred to as threshold).