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

Introduction Hepatitis 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...

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Main Authors: Jeremy Horwood, Andrew Radley, John F Dillon, Peter Vickerman, Rory N Gunson, Mary Ramsay, Chris Metcalfe, William Hollingworth, Hannah Fraser, Helen Harris, Ellen Heinsbroek, Lawrie Elliott, Paul Flowers, Sema Mandal, Matthew Hickman, David Goldberg, Natasha Martin, Emma Hamilton, Daniela De Angelis, Graham Foster, Peter Donnan, Ann Eriksen, Samreen Ijaz, David Liddell, Lewis J Z Beer, Kate Drysdale, Rachel Glass, Lesley Graham, Ross Harris, Vivian Hope, Sarah Karen Inglis, Hamish Innes, Athene Lane, Jade Meadows, Andrew McAuley, Stephanie Migchelsen, Alex Murray, Gareth Myring, Norah E Palmateer, Anne Presanis, Pantelis Samartsidis, Ruth Simmons, Katy Sinka, Gabriele Vojt, Zoe Ward, David Whiteley, Alan Yeung, Sharon J Hutchinson
Format: Article
Language:English
Published: BMJ Publishing Group 2019-09-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/9/9/e029538.full
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author Jeremy Horwood
Andrew Radley
John F Dillon
Peter Vickerman
Rory N Gunson
Mary Ramsay
Chris Metcalfe
William Hollingworth
Hannah Fraser
Helen Harris
Ellen Heinsbroek
Lawrie Elliott
Paul Flowers
Sema Mandal
Matthew Hickman
David Goldberg
Natasha Martin
Emma Hamilton
Daniela De Angelis
Graham Foster
Peter Donnan
Ann Eriksen
Samreen Ijaz
David Liddell
Lewis J Z Beer
Kate Drysdale
Rachel Glass
Lesley Graham
Ross Harris
Vivian Hope
Sarah Karen Inglis
Hamish Innes
Athene Lane
Jade Meadows
Andrew McAuley
Stephanie Migchelsen
Alex Murray
Gareth Myring
Norah E Palmateer
Anne Presanis
Pantelis Samartsidis
Ruth Simmons
Katy Sinka
Gabriele Vojt
Zoe Ward
David Whiteley
Alan Yeung
Sharon J Hutchinson
author_facet Jeremy Horwood
Andrew Radley
John F Dillon
Peter Vickerman
Rory N Gunson
Mary Ramsay
Chris Metcalfe
William Hollingworth
Hannah Fraser
Helen Harris
Ellen Heinsbroek
Lawrie Elliott
Paul Flowers
Sema Mandal
Matthew Hickman
David Goldberg
Natasha Martin
Emma Hamilton
Daniela De Angelis
Graham Foster
Peter Donnan
Ann Eriksen
Samreen Ijaz
David Liddell
Lewis J Z Beer
Kate Drysdale
Rachel Glass
Lesley Graham
Ross Harris
Vivian Hope
Sarah Karen Inglis
Hamish Innes
Athene Lane
Jade Meadows
Andrew McAuley
Stephanie Migchelsen
Alex Murray
Gareth Myring
Norah E Palmateer
Anne Presanis
Pantelis Samartsidis
Ruth Simmons
Katy Sinka
Gabriele Vojt
Zoe Ward
David Whiteley
Alan Yeung
Sharon J Hutchinson
author_sort Jeremy Horwood
collection DOAJ
description Introduction Hepatitis 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 analysis We 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 dissemination Extending 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.
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spelling doaj-art-21ec6d8a840c4638850edfdedff2634a2025-08-20T02:06:58ZengBMJ Publishing GroupBMJ Open2044-60552019-09-019910.1136/bmjopen-2019-029538Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)Jeremy Horwood0Andrew Radley1John F Dillon2Peter Vickerman3Rory N Gunson4Mary Ramsay5Chris Metcalfe6William Hollingworth7Hannah Fraser8Helen Harris9Ellen Heinsbroek10Lawrie Elliott11Paul Flowers12Sema Mandal13Matthew Hickman14David Goldberg15Natasha Martin16Emma Hamilton17Daniela De Angelis18Graham Foster19Peter Donnan20Ann Eriksen21Samreen Ijaz22David Liddell23Lewis J Z Beer24Kate Drysdale25Rachel Glass26Lesley Graham27Ross Harris28Vivian Hope29Sarah Karen Inglis30Hamish Innes31Athene Lane32Jade Meadows33Andrew McAuley34Stephanie Migchelsen35Alex Murray36Gareth Myring37Norah E Palmateer38Anne Presanis39Pantelis Samartsidis40Ruth Simmons41Katy Sinka42Gabriele Vojt43Zoe Ward44David Whiteley45Alan Yeung46Sharon J Hutchinson477 Department of Population Health Sciences, University of Bristol, Bristol, UKSchool of Medicine, University of Dundee, Dundee, UKLiver Group, University of Dundee Division of Cardiovascular and Diabetes Medicine, Dundee, UKPopulation Health Sciences, University of Bristol, Bristol, UK10 West of Scotland Specialist Virology Centre, Glasgow Royal Infirmary, Glasgow, UKNational Infection Service, UK Health Security Agency, London, UK1 Bristol Trials Centre, University of Bristol, Bristol, UKPopulation Health Sciences, University of Bristol Medical School, Bristol, UKpostdoctoral researcherWestern General Hospital, NHS Lothian, Rheumatology, Edinburgh, United Kingdom10 National Infection Service, Public Health England, London, UK3 Glasgow Caledonian University, Glasgow, UK11 University of Strathclyde, Glasgow, UKBlood Safety, Hepatitis, STI and HIV Division, UK Health Security Agency, London, UKBristol Medical School, University of Bristol, Bristol, UK1 Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK12 Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, UK16 Scottish Drug Forum, Edinburgh, UKMRC Biostatistics Unit, University of Cambridge, Cambridge, UK12Queen Mary University College Londonprofessor of epidemiology and biostatistics, director of Dundee Epidemiology & Biostatistics Unit (DEBU), co-director of Tayside Clinical Trials Unit (TCTU)8 Tayside Health Board, Dundee, UK10 National Infection Service, Public Health England, London, UK11 Scottish Drugs Forum, Edinburgh, UK13 Tayside Clinical Trials Unit, Tayside Medical Science Centre, University of Dundee, Dundee, UK5 Blizard Institute, Queen Mary University of London, London, UK10 National Infection Service, Public Health England, London, UK6 Public Health Scotland, Edinburgh, UKBlood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Division, UK Health Security Agency-Colindale, London, UK18 Liverpool John Moores University, Liverpool, UKTayside Clinical Trials Unit, University of Dundee, Dundee, UK9 School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UKPopulation Health Sciences, University of Bristol Medical School, Bristol, UK1 Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK3 Glasgow Caledonian University, Glasgow, UK10 National Infection Service, Public Health England, London, UK16 Scottish Drug Forum, Edinburgh, UK1 Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK3 Glasgow Caledonian University, Glasgow, UKMRC Biostatistics Unit, University of Cambridge, Cambridge, UKMRC Biostatistics Unit, Cambridge, UKBlood Safety, Hepatitis, Sexually Transmitted Infections (STI) and HIV Division, UK Health Security Agency-Colindale, London, UKBlood Safety, Hepatitis, STI and HIV Division, UK Health Security Agency, London, UK1 School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK1 Population Health Sciences, Bristol Medical School, Bristol, Bristol, UK1 Department of Nursing and Community Health, Glasgow Caledonian University School of Health and Life Sciences, Glasgow, UKDepartment of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California, USA1 Centre for Living, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UKIntroduction Hepatitis 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 analysis We 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 dissemination Extending 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.https://bmjopen.bmj.com/content/9/9/e029538.full
spellingShingle Jeremy Horwood
Andrew Radley
John F Dillon
Peter Vickerman
Rory N Gunson
Mary Ramsay
Chris Metcalfe
William Hollingworth
Hannah Fraser
Helen Harris
Ellen Heinsbroek
Lawrie Elliott
Paul Flowers
Sema Mandal
Matthew Hickman
David Goldberg
Natasha Martin
Emma Hamilton
Daniela De Angelis
Graham Foster
Peter Donnan
Ann Eriksen
Samreen Ijaz
David Liddell
Lewis J Z Beer
Kate Drysdale
Rachel Glass
Lesley Graham
Ross Harris
Vivian Hope
Sarah Karen Inglis
Hamish Innes
Athene Lane
Jade Meadows
Andrew McAuley
Stephanie Migchelsen
Alex Murray
Gareth Myring
Norah E Palmateer
Anne Presanis
Pantelis Samartsidis
Ruth Simmons
Katy Sinka
Gabriele Vojt
Zoe Ward
David Whiteley
Alan Yeung
Sharon J Hutchinson
Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
BMJ Open
title Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
title_full Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
title_fullStr Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
title_full_unstemmed Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
title_short Evaluating the population impact of hepatitis C direct acting antiviral treatment as prevention for people who inject drugs (EPIToPe) – a natural experiment (protocol)
title_sort evaluating the population impact of hepatitis c direct acting antiviral treatment as prevention for people who inject drugs epitope a natural experiment protocol
url https://bmjopen.bmj.com/content/9/9/e029538.full
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