Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)

Abstract

IntroductionHepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV ‘Treatment as Prevention’ (TasP) in PWID.Methods and analysisWe plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome – chronic HCV prevalence in PWID – is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a ‘virtual cohort’ of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes.Ethics and disseminationExtending HCV community care pathways is covered by ethics (ERADICATE C,ISRCTN27564683, Super DOT C Trial clinicaltrials.gov:NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England.

Population impact of direct-acting antiviral treatment on new presentations of hepatitis C-related decompensated cirrhosis: a national record-linkage study

“…Sixth, while we have examined the scale-up of DAAs and associated impact for a predominantly injecting drug use-related HCV epidemic, we have not considered those currently injecting separate from those who injected in the past. Data from a national survey in Scotland however show that appreciable scale-up of DAAs among the population continuing to inject drugs did not occur until towards the end of the study period considered here (during 2017–2018) and thus is the subject of an ongoing study to determine whether treatment leads to prevention benefit 38 39…”

Provider‐related barriers and enablers to the provision of hepatitis C treatment by general practitioners in Scotland: A behaviour change analysis

“…Contemporary DAA treatment allows the dogmatic pre ‐treatment assessment of liver fibrosis to be rethought, and a simpler pathway to treatment initiation forged. GP provision of HCV treatment may benefit from a ‘treat and refer’ model of care, rather than the ‘refer and treat’ status quo of many community‐based pathways 8 …”

“…However, the role of non‐specialist clinicians in prescribing that treatment has received scant attention to date. Community‐based pathways in Scotland function as ‘outreach’ models of care, relying on specialist clinicians prescribing DAA treatments in non‐specialist settings 8 . Such specialist clinicians comprise hospital‐based doctors, nurses and pharmacists working in hepatology or infectious diseases.…”

Excitable models: Projections, targets, and the making of futures without disease

“…Enumerated projections – including those abstracted from more ‘theoretical’ rather than ‘empirical’ models – perform a bridge in an apparent evidence gap (Morgan & Morrison, 1999 ), including in policy situations when so‐called ‘hard evidence’ of intervention effects from randomised controlled trials or observational studies are unavailable (Wood et al, 1998 ). We can see this performance at work in the field of global disease control, where the modelled projection of viral elimination through reduced incidence of infection is indexed to population‐level effects anticipated in the near future (usually somewhere between 10 and 20 years in the case of hepatitis C) which have yet to be materialised as ‘real world’ outcomes through intervention trials (Hickman et al, 2019 ). In epidemics, models work as devices to make evidence to enable policy actions in the face of uncertainty, even as outbreaks emerge (Lakoff, 2017 ; Rhodes & Lancaster, 2020 ).…”