Economic analysis to support NHS implementation of hepatitis c drugs: scoping study

A number of new treatments for chronic hepatitis C have recently undergone or are currently undergoing appraisal of their value to the National Health Service (NHS) in England and Wales by the National Institute of Health and Care Excellence (NICE): simeprevir, sofosbuvir, ledipasvir-sofosbuvir, daclatasvir and ombitasvir-paritaprevir-ritonavir with or without dasabuvir. These new treatments are an addition to the existing interferon-based therapies: dual therapy with interferon and ribavirin, and triple therapy with boceprevir or telaprevir with interferon and ribavirin. The aim of this work is to provide a basis for decisions about substantive research which could be undertaken to inform NHS decisions about the implementation of NICE guidance on hepatitis C drugs.

The NICE guidance has considered whether, for a given patient at a particular stage in their disease and treatment for hepatitis C, one of the new drugs might provide value. However, the results do not lend themselves to directly inform implementation strategies about prioritising access to new drugs for hepatitis C in a way that maximises health benefits and value to the NHS. As a result, there are four key challenges raised by the NICE guidance in the operationalization of its implementation by NHS England:

1. No clear guidance on how to prioritise implementation of the range of treatments recommended as options. The NICE recommendations implicitly include watchful waiting and treatment sequencing strategies given the different recommendations by disease severity and prior treatment experience. The lack of direct comparison between these strategies and a ‘treat all’ strategy makes it difficult to judge how best to implement guidance.

2. No clear guidance on the role of treatment in controlling the hepatitis C epidemic. The cost-effectiveness analyses that informed the NICE recommendations omitted the risk of patient patients with hepatitis C infecting others. However, treatment may reduce the number of infected patients and hence reduce the number of people infected. The impact of excluding infection depends on the effectiveness and costs of treatment, the prevalence of the disease and the probability of risky behaviours by infected patients.

3. Uncertainty in the benefits of the new treatments on the health benefits to patients and costs to the NHS. Given the small evidence base composed largely of single arm studies, there may be considerable decision uncertainty associated with recommending new treatments as cost-effective based on current information. This uncertainty imposes potentially high costs on the NHS and may imply a high value for additional research to reduce evidential uncertainty. Further analysis can inform the extent of decision

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uncertainty, quantify the value of additional research and help inform implementation of NICE guidance.

4. The potential for large upfront demand on NHS resources. In order to release funding to offer these treatments to all eligible patients, other interventions that the NHS currently offers can no longer be funded. If the scale of demand leads to the displacement of interventions that offer more health benefits than the new treatments for chronic hepatitis C, then offering the new drugs to all eligible patients is likely to result in a net loss of health. For these reasons, implementation of NICE guidance should be informed by an analysis considering all costs and benefits to the NHS.

There is a priority for cost-effectiveness analysis which builds on NICE guidance to indicate the optimal implementation strategy for each patient group. The proposed research would include:

 A direct comparison of all the relevant treatment options, including new treatments, watchful waiting, and treatment sequences.

 Subgroup analyses by patient characteristics that affect the costs or benefits of treatment, such as genotype, prior treatment experience, interferon eligibility and severity of disease.

 The impact of uncertainty in the effects of treatment on the costs and benefits of the optimal strategies.

 The costs and benefits of reducing onward transmission and reinfection.

 The implications of current NHS England commissioning policy for treating those with decompensated cirrhosis and its impact on extending access for people with cirrhotic and non-cirrhotic disease.

 The level of investment to increase treatment uptake that is warranted alongside the optimal strategies in each of the patient groups.

 The characteristics required of any further new treatment in order for it to offer value to the NHS (threshold levels of effectiveness and cost).