Frequency of visual field testing when monitoring patients newly diagnosed with glaucoma

Transcription

1 HSR Protocol - project ref: 10/2000/68 Version: Version 1 Date: 17 March 2011 Frequency of visual field testing when monitoring patients newly diagnosed with glaucoma Chief investigator Professor David P. Crabb Sponsor University of Dundee Funder HSR Programme NIHR Portfolio number ISRCTN registration (if applicable) [10/2000/68] [Crabb] protocol version: [1] [ ] 1

2 Frequency of visual field testing when monitoring patients newly diagnosed with glaucoma 1. Aims/Objectives People with glaucoma represent a major workload of NHS eye services. The recent NICE guidelines for glaucoma made an important recommendation for research to improve patient care in the future, including a call to establish the clinical-effectiveness and cost-effectiveness of using different monitoring intervals to detect disease worsening or stability in patients diagnosed with the condition. The purpose of this project is to explore this question by using existing NHS data on current practice and provide new research knowledge through modelling. The project will focus on the mainstay measurement for glaucoma monitoring, visual fields. Objectives To survey and establish the current use of visual field (VF) resources and to determine current practice in terms of follow-up for the newly diagnosed patient in NHS glaucoma services across England and Wales. To also explore patient s views on frequency of testing for the follow-up of their condition. To retrospectively investigate the distribution of the rate of progression in a large cohort of patient records. This will involve the interrogation of more than 160,000 VF tests, equivalent to around 8 million data points. Information about rates of progression in representative groups of glaucoma patients under clinical care will help us to model typical results achieved with currently available treatment modalities and inform about the magnitude of current and projected future visual function deficits caused by glaucoma. To further develop our published model for generating virtual series of VFs in order to explore different follow-up schemes. Different schemes, for example annual testing against say three tests per year, will be assessed for rates of false negative and false positive outcomes in determining glaucomatous progression. The model will include a final VF outcome during patient s expected remaining lifetimes if observed rates of progression would remain unchanged. To refine an existing health economics model for glaucoma care to estimate the clinical-effectiveness and cost-effectiveness of alternative monitoring regimes (including the recommended EGS strategy of 6 fields in the first 2 years) on long term health outcomes. This model will incorporate costs for VF testing. To inform, from the results of our modelling the most cost-effective of our alternative VF monitoring strategies. To inform, from the results of our modelling, the design of future research, specifically an RCT as outlined in the NICE glaucoma guidelines, if required. [10/2000/68] [Crabb] protocol version: [1] [ ] 2

3 2. Background and Need Comprehensive guidelines for the diagnosis and management of glaucoma were published by NICE in 2009, revealing a complete absence of research evidence about how patients with the condition should be monitored over time. The NICE Guideline Development Group published a few important recommendations for essential future research ( Their very first question was:...what is the clinical effectiveness and cost effectiveness of using different monitoring intervals to detect disease progression in people with glaucoma who are at risk of progression?... The importance of this question is emphasised further by the statement,...the answer to this question is key to recommendations on chronic disease monitoring intervals... A randomised comparative trial (RCT) of different monitoring intervals was suggested; this would be a major undertaking but likely to be helpful in gaining a better evidence on a range of issues with NHS glaucoma management. The audit and modelling work proposed in this study would be an important step towards planning an RCT and justifying the cost of such a study. The issue is not just identifying progression but being able to do something about it in a way that makes a difference to patients that is worth the cost. Rates of visual field (VF) progression in clinical populations vary widely between patients and timely detection of progression requires accurate and consistent measurement of VFs over years. The European Glaucoma Society (EGS) currently recommends that all newly diagnosed glaucoma patients should be tested 3 times per year during the first 2 years after diagnosis. In this way rate of loss can be determined early, and rapidly changing eyes be revealed with great certainty. This is supported by recently published work (Chauhan et al 2008): central to this work was the important idea that a sufficient number of tests must be performed in a patient over time to give any chance of separating true disease progression from the measurement variability inherent in the VF data. This conclusion is analogous to the accepted idea that a clinical trial will not be sufficiently powered to detect an experimental effect if insufficient numbers are recruited. The notion that three tests should be performed per year to adequately measure visual progression is also supported by evidence from previous studies conducted by the lead applicant using computer simulation and others using retrospective examination of a large visual field data set (Crabb and Garway-Heath 2009; Gardiner and Crabb 2002). However, the 6 VFs in 2 years approach implies that a patient doing well under treatment receives the same number of tests as a patient heading for blindness. The current NICE guidelines state that VF monitoring should be 2 to 6 months for newly diagnosed or suspected glaucoma patient and 6 to 12 months for stable follow-ups. [10/2000/68] [Crabb] protocol version: [1] [ ] - 3 -

4 A pilot audit of the glaucoma service at Moorfields Eye Hospital NHS Trust indicates that it costs approximately 55 for every VF test, including staffing and overheads. The NICE glaucoma guidelines indicated that currently there are 9263 new cases per year (excluding suspects or patient suffering from ocular hypertension). So each VF test in the annual cohort of newly diagnosed patients will cost approximately 0.5 million and that over two years about 3 million could be spent if six tests are done for that one single cohort alone. Clearly these are large sums of NHS money and optimising these guidelines for VF testing could involve savings, but they may be offset by reduced detection rates of visual loss in patients that might in turn cost the NHS because more advanced disease is more expensive to care for, along with the socioeconomic burden of more patients potential falling into visual disability. This example illustrates why this problem is absolutely ripe for modelling, both in terms of detecting VF progression and the health economics. Moreover, there is absolutely no evidence base for how the EGS or NICE guidelines about monitoring are currently being used, or what might even be feasible with the resources available; the latter must be the starting point for any research in this area. This research is likely to identify new ways of working that enhance opportunities for health promotion or quality and safety of care. Benefits may also arise from improving the acceptability and effectiveness of care, cost effectiveness to the NHS, better targeting of services or equity of access to care. The focus of the expressed research need is consistent with the wider mission of the HSR programme and its primary orientation towards the organisation and delivery of healthcare. 3. Methods The project is made up of two integrated work packages and what follows is detail of the methodology to be used. Work-Package 1 WP1: Stage 1 (WP1.1) A clinical audit of approximately 400 patient episodes will be conducted at the glaucoma service at Moorfields Eye Hospital to establish current practice regarding follow-up intervals for patients under current care. The audit collection will take place over a one week period and will capture the clinical practice of all twelve consultants in the glaucoma service at Moorfields Eye Hospital. Our starting point will be to determine information on data collected at an episode: functional measures, age, ocular co-morbidity; treatment; intraocular pressure (IOP); previous IOP; target IOP; visual fields; optic disc assessment; imaging; follow-up interval assigned; age; ethnicity; sex and other variables. Moorfields has a number of outreaches, where practice may differ and they will be encompassed in the audit. Example data to be recorded will be patient s phenotype and status, management plan, and follow-up details. Data will be also recorded on the type of clinical measurements and tests taken during their current follow-up, specifically the number and frequency of visual field tests. The work will be performed by the project RA under the [10/2000/68] [Crabb] protocol version: [1] [ ] - 4 -

5 direction of Garway-Heath and Malik (See collaborators). This preliminary survey will test the hypothesis that follow-up intervals for patients with glaucoma are highly variable in this clinic. The results from this audit will be used to help inform the design of questions to be used in WP1.2 and WP 1.3 of this work package. The results will be written up into a short paper for a clinical journal within the first 6 months of the project. WP1: Stage 2 (WP1.2) A survey will be designed, based in part on the results from stage 1, which will be sent to a sample of Service Managers for Ophthalmology. This survey will focus on extracting information around current service utilisation of Ophthalmology services for glaucoma. Questions will be set to establish the number VF tests performed and (critically for this stage of the WP) yield information on associated costs, equipment and staffing. The survey will require the manager to access a number of case notes and from this to identify the total number of visits to the Ophthalmology department (whether for visual fields or consultant review), the reason for the visit and the time line for these visits. The mechanisms for collecting this data are already easily accessible to some units because of a recent NPSA alert and response required a not dissimilar audit. However, since practice may have changed as a result of this audit the notes examined must be within the last year i.e. post this audit. Ophthalmology managers will be identified by using the North London Managers Group as a core unit and snowballing from there until 10 units are reached. The incentive for these managers will be access to comparable data from other units which will assist in their service planning, and the ability to close the loop on the previous NPSA related audit if carried out. A primary outcome will establish the number of VF tests carried out in newly diagnosed patients and see how this complies with current guidelines. The results from this survey will provide a report or consultation document that will be used in stage 3 of the WP. This work will be performed by the project RA and Lemer, who has conducted such surveys before in her role in the North London Managers Group including the NPSA audit, and the mechanics for the survey ( are already in place. WP1.2 will be mainly a quantitative based survey. Five pilot interviews with Ophthalmology managers will be identified by using the North London Managers, to be conducted by Lemer and these will use grounded theory and be semi structured in nature to illicit appropriate interview questions and structures for WP1.3. WP1: Stage 3 (WP1.3) A series of interviews with Heads of Glaucoma services at a sample of NHS Hospital Trusts will be undertaken, facilitated by research links established as part of the UK Glaucoma Treatment Study (PI: Garway-Heath), which has patient centres in Birmingham, Bristol, Cambridge, Cheltenham, Sunderland, Huddersfield, Norwich and Peterborough. The interviews will be carried out by the RA. These interviews will mould the results from the survey of practice into a report that will then be considered by the advisory group (at 12 months), members of which include a patient representative, a chairmen patient advisory group, a national expert in ophthalmic nursing, a glaucoma measurement technician with more than ten years of testing, chaired by a [10/2000/68] [Crabb] protocol version: [1] [ ] - 5 -

6 leading researcher in the area of glaucoma management. A series of qualitative, semi-structured interviews, analysed by framework analysis will be used to capture information about the different types of follow-up that are currently employed for NHS glaucoma patients. These interviews will be conducted with heads of glaucoma services at eight regions already specified, and now extra participation from Manchester, Nottingham and two centres in London. One randomly selected glaucoma consultant from each centre will also be interviewed. The interview questions will be formulated from WP1.1 and 1.2. We have added the considerable expertise of Kandy Woodfield to the research team who will provide guidance and direct supervision on the qualitative research, including the analysis, to be undertaken in both WP1.3 and WP1.4 (below). Woodfield is the Director of NatCen Learning. NatCen (the National Centre for Social Research; ) is the UK s leading centre for independent social research. The RA will also attend two courses at NatCen one of which will be on using Framework software. A report, based on WP1.3, will be written on current practice for follow-up plans for newly diagnosed glaucoma. In the event of a recommendation for a clinical trial this information will establish an evidence base for a standard care arm of such a trial. WP1: Stage 4 (WP1.4) We will conduct two dual-monitored focus groups with patients (8-10 patients in each) recruited from Moorfields Eye Hospital to examine patients opinion on follow-up appointments for glaucoma. This will, however, be an exploratory study because it will use patients from one centre. (An ethnic mix of patients will be deliberately sampled). These focus groups will take place at City University in the interactive laboratory, providing patient insight that would be less accessible without interaction found in a group setting. Fortunately, Bronze, our patient co-applicant, has experience in conducting focus groups; for 20 years, she has worked in publishing where she has heavily relied on focus group testing to validate what they do, as well as manoeuvre commercial interests, if need be, to support the publishing projects. She has agreed to co-monitor these focus groups and will, therefore, uniquely provide empathy toward the patients. Woodfield will provide important supervision of WP1.4. Work Package 2 WP2.1: Visual field progression modelling Crabb has previously developed a computer model for generating series of visual fields (Crabb and Gardiner 2002; Wall et al 2009). In short, the virtual eye can produce series of VFs with known properties (baseline sensitivity values, length of series, frequency of testing, rates of loss) and adds variability or noise around each measured value by sampling randomly from a known distribution with mean zero and with a standard deviation which increases as the underlying sensitivity decreases. For illustration, a VF for a Virtual Eye is constructed and is shown in greyscale form at the top of adjacent. This left eye has an early to moderate VF defect, perhaps typical of a patient presenting at clinic. The individual values that make up this field are assumed to be the true [10/2000/68] [Crabb] protocol version: [1] [ ] - 6 -

7 physiological values for this eye; these will not be the same as the measured or estimated values derived at a VF test. Three typical examples of the latter, where noise has been added via the model to the true visual field, are shown as greyscales at the bottom of figure. These can be used to model series of eyes to get estimates of true detection of progression as well as false-positive (FP) and false negative (FN) results. The first stage of the modelling will be to estimate distributions of the rate of progression in a large cohort of 160,000 VFs, under standard care, already archived from Moorfields Eye Hospital. Information about rates of progression in representative groups of glaucoma patients under clinical care will help us to model typical results achieved with currently available treatment modalities and inform about the magnitude of current and projected future visual function deficits caused by glaucoma. Then using a recent method that we have developed for producing series of modelled visual fields (Crabb and Garway- Heath 2009) we can examine the performance of different test frequency affecting prediction of patients with rapid progression: these are patients under treatment that will continue to lose vision at a rate of loss which will lead to visual disability. The later will be defined as visual impairment/blindness or an alternative earlier milestone to blindness: cessation of driving. We have recently published work that uses this technique (Owen et al 2008). The model will be developed in the statistical programming language R and will be made freely available to other researchers via a www page hosted at City. The work will be presented as VF model in a separate paper to be submitted to Investigative Ophthalmology and Visual Science. The outputs from the model will be known detection rates of rapid progressing patients for different follow-up periods and associated FP and FN rates. For example, values will be generated from 1, 2, 3 and 4 tests per year covering the suggested range of the NICE guidelines. We will also produce sequences where test interval is varied to get better estimates of the rate of VF Progression. We already have results to show some advantages of this wait and see approach (Crabb and Garway-Heath 2009); the model has previously indicated that rates of VF loss can be estimated more accurately if, for example, more baseline measurements are acquired but with fewer patient visits. This might, for example, fit with the NHS one stop approach to monitoring which might be easier for patients and less demanding on NHS resources. This data will be fed into the economic model. The work for this part of WP2 will be done by the RF and supervised directly by Crabb and Garway-Heath. WP2.2: Economic modelling. A full economic evaluation of the costs and consequences of the different frequency of follow-up testing identified in the first part of WP2 will be instituted. This model will build on the considerable experience gained from the developments of the economic evaluation modelling of screening for glaucoma (Burr et al 2007; Hernandez et al 2008). This economic modelling was extensively used and cited throughout the 2009 NICE guidelines for the [10/2000/68] [Crabb] protocol version: [1] [ ] - 7 -

8 diagnosis and management of glaucoma ( However, for this current investigation, an individual sampling model typically referred to as a Discrete Event Simulation (DES) will be used in preference to the previously used Markov Model. DES has also been recently used with glaucoma management (vangestel et al 2010). The cycle time in a Markov model is fixed, whereas the specific aim of this particular economic model will be to explicitly evaluate the effects of altering the frequency of visits on costeffectiveness outcomes (Karnon 2003). The DES model will allow for the latter and will also provide a finished model allowing for relatively easy adjustments to future research questions, which is a pertinent to the aim of recommendation for clinical trial design of different follow-up patterns. The typical elements of a DES model are: entities (patient or eye); attributes (sex and age); events (rapid progression); relationships that link the components of the model together; and outcomes (detection rate, lifetime costs, costs of FP and FN decisions). The simulation of visual field progression (WP2.1) will provide input predictors for this economic model. The model structure will recreate alternative care pathways describing individuals going through different follow-up schemes (e.g. different VF testing intervals). The model will allow for costs of initial visual fields testing (e.g. healthcare visits, staff time, equipment and even travel costs [Sharma et al 2010]) together with subsequent relevant treatment and follow-up costs. The effects of FP and FN test results will also be considered. These will have implications in terms of costs (e.g. unneeded treatment for those with FP results). The economic modelling will closely adhere to the NICE methodology guidelines to conduct this economic evaluation. The perspective of the analysis will be that of the NHS; therefore, NHS relevant cost categories will be included. Outcome will be an appropriate measure of clinical effectiveness (e.g. number of individuals not progressing beyond a certain threshold of visual function loss [see rapid progressors in WP2.1]) and also quality adjusted life years (QALYs). Time horizon for the model is likely to be lifetime of the individuals. Data to populate the model will be mainly obtained from the proposed visual field progression and frequency of testing simulations (WP2.2) and the retrospectively investigated distribution of the rate of progression in a large cohort of patient records held at Moorfields Eye Hospital (WP2.2), as well as some structured searches of the literature. Costs will be obtained from typical public sources: for example, the Personal Social Services Research Unit (PSSRU) for staff unit costs, British National Formulary (BNF) for cost of medicines, NHS Reference Costs for health interventions. In addition to NHS costs we will attempt to estimate the attendance at clinic and travel costs using previously published results. Parameter uncertainty will be addressed by conducting deterministic and probabilistic sensitivity analyses. Heterogeneity will be tackled by running models for different sub-groups with simple estimates of risk to progression. Other sources of uncertainty due, for instance, to the assumptions made in the models (e.g. structural uncertainty) will be explored if considered necessary. Deterministic results will be expressed in incremental cost effectiveness ratios (ICERs) using a suitable unit of effectiveness avoided, but also QALYs. Probabilistic results will be presented using scatter plots and/or cost-effectiveness acceptability curves (CEACs). A value of information analysis (Briggs et al 2006) will be conducted [10/2000/68] [Crabb] protocol version: [1] [ ] - 8 -

9 to identify the expected value of perfect information over the expected lifetime of the surveillance strategies considered and the value of further research to identify more precise and reliable estimates of parameters of the economic model. Value of information analyses can be compared with the cost of conducting further research in order to reduce the uncertainty in the model. The deliverables from this part of WP2 will be true economic measures, including modelled estimates of costs to the NHS of follow-up, treatment and subsequent monitoring of cases, incremental cost per case detected, quality adjusted life years over the model time horizon (e.g. patient lifetime), incremental cost (treatment and follow-up) per QALY 1 of alternative follow-up regimes compared with current practice (Burr et al 2007). Achieving transparency in model structure and outcomes will be assisted by the aim of reporting the economic model in a clinical ophthalmology journal. The work for this part of WP2 will be done by the RF and Hernandez. 4. Contribution of existing research Results will be communicated to academic, policy and service audiences. The proposed work will lead to peer-reviewed publications. In particular Crabb will set up a committee meeting with the head of glaucoma services from a number of PCTs and also a special interest group meeting as part of the annual United Kingdom and Eire Glaucoma Society meeting in December Moreover, Crabb, Garway-Heath and Lemer will directly report results to NHS management and leadership community: the proposed work has important implications for service delivery that could lead to enhanced public service and community engagement. 5. Plan of Investigation Plan of investigation and timetable Project Management (Month 1: October 2011) Month Milestones Pre-funding Research and Ethics 1 (Sept. 2011) 1st project meeting 5 2nd project meeting. 6 1st Advisory group meeting 11 3rd project meeting (Short report to HSR) 12 2nd Advisory group meeting 17 Final project meeting 18 Final report written Work Packages Month Milestones 1-2 WP1 (Stage 1: Pilot MEH Audit) 1- WP2 (Start WP1 (Stage 2: Short quantitative survey and pilot interviews) 4-8 WP1 (Stage 3: interviews with Heads of Glaucoma services) [10/2000/68] [Crabb] protocol version: [1] [ ] - 9 -

10 9-10 WP1 (Stage 4: Patient focus groups) 9- Complete WP2.1 Visual Field model/simulation WP1 (Write-up) 15 Complete WP2.2 Health Economic DES model WP2 (write-up) 6. Approval by Ethics Committees The proposal complies with the Research Governance Framework and will be monitored by the City University Senate Ethics committee; this conforms to recognised high standards of research governance and abides by the 1998 Data Protection Act. There are no outstanding R&E conditions. We will get full R&E approval before the start of the project (June 2011). IPD from Moorfields Eye Hospital will be interrogated as part of this study. This database is anonymised and is being used as an on-going research resource and is exempt under Section 60 of the Health and Social Care Act Project Management The day-to-day running of the study will be the responsibility of the principal investigator (Crabb Budgeted time at 20% across the whole project) supported by the research fellow (RF). All five applicants (Crabb, Garway- Heath, Lemer, Hernandez and Bronze) will meet at the start of the project and at 6 monthly intervals, with separate meetings where necessary; they will provide strategic, management and content expertise to the study. A project advisory group chaired by Jennifer Burr of University of Aberdeen will advise at key milestones in the project (6 and 12 months). 8. Service users/public involvement: Carol Bronze is a joint applicant on this proposal: she is a glaucoma patient who has been attending clinics at Moorfields Eye Hospital for around 20 years. She will be involved in the study design as a patient representative and will assist in the final written report. David Wright, Chief Executive of the International Glaucoma Association (IGA), will be a member of the project advisory group. The IGA is the charity for people with glaucoma, with the mission to raise awareness of glaucoma, promote research related to the disease and to provide support to patients and all those who care for them. 9. Expertise and justification of support required Applicants This research requires a multi-disciplinary approach and the co-applicants have expertise in ophthalmology, glaucoma, visual fields, NHS management and service provision, clinical audit, modelling, statistics, health economics and patient perspective. David Crabb is Professor of Statistics and Vision Research in the Department of Optometry and Visual Science at City University London. The focus of his research laboratory is on measurements in glaucoma, especially functional measurements, such as visual fields and evaluating how these relate to activities of daily living. The laboratory aims to develop clinically useful information management tools for these measurements, and provide efficient [10/2000/68] [Crabb] protocol version: [1] [ ]

11 clinical trial design to develop safer and more targeted treatments with respect to disease progression. Crabb is both widely published and holder of several grants in the area of visual fields and glaucoma. David Garway-Heath is International Glaucoma Association Professor of Ophthalmology and Glaucoma Theme Lead at the Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and the UCL Institute of Ophthalmology, London. He is also Honorary Consultant Ophthalmic Surgeon at Moorfields Eye Hospital. Garway-Heath is widely regarded as a leading international expert in glaucoma research. He has recently been awarded the prestigious status of NIHR Senior Investigator (only six such positions in Ophthalmology in the UK). He serves as an Executive Member of the Glaucoma Research Society (GRS) and is Founder Member of the Scientific Committee of the European Glaucoma Society (EGS). Claire Lemer is Operations Manager for Ophthalmology at the North Middlesex University Hospital Trust. She has extensive expertise in medical management having written two recent books, Clinical Leadership: Bridging the divide (Quay Books, 2009) and MBA for Medics (Radcliffe, 2010). She developed an interest in management as a result of spending time at the Department of Health and WHO. During this time she developed expertise in interviewing stakeholders involved in quality improvement in health management. She held a prestigious Commonwealth Fund/Health Foundation Harkness Fellowship in Health Policy at Brigham and Women s Hospital in Boston (US), where she researched the effects of communication in paediatric medication safety. Lemer has an MD focused on Quality Improvement, an MPH from Harvard and has recently completed an MBA from Oxford. Lemer is Company Director of Diagnosis: a Clinical Leadership Social Enterprise encouraging development of managerial and leadership skills amongst clinicians. Rodolfo Hernandez is a Research Council UK fellow in economic modelling at the Health Services Research Unit (HSRU) at the University of Aberdeen, and has an extensive portfolio of experience of economic modelling in glaucoma. Hernandez is the author of the health economics model for glaucoma (Health Technol Assess 2007;11(41)) that was cited extensively throughout the NICE glaucoma guidelines. He is one of the principal health economists on the HSRU s MRC funded trial platform grant considering the intervention and outcome components of a proposed randomised controlled trial of screening for glaucoma. He is also the health economist on other NIHR HTA programmes at the HSRU in Aberdeen. Carol Bronze is a glaucoma patient who has been attending clinics at Moorfields Eye Hospital for around 20 years. She has participated as a subject in many research studies and has been involved as a patient representative on the Moorfields Motion Displacement Test project ( Bronze is editorial and creative director for Publicis-Blueprint magazines, London. Consultant: Kandy Woodfield will act as a consultant on WP1.3 and WP1.4. [10/2000/68] [Crabb] protocol version: [1] [ ]

12 She is the Director of NatCen Learning. NatCen (the National Centre for Social Research; ) is the UK s leading centre for independent social research. Researchers from NatCen have expertise in relation to qualitative methods for applied policy research. Woodfield has over 15 years experience of conducting high-quality applied social research across a range of substantive policy areas including, socio-legal issues; education and learning; political and social attitudes; unemployment and disability research. Woodfield has a wealth of experience in interviewing and focus group techniques and along with colleagues pioneered the development of NatCen's tool for qualitative data analysis - FrameWork. She will provide expert advice and guidance to the research team on the design, collection and analysis of qualitative data from WP1.3 & WP 1.4. Staffing, management and organisation 0.6FT Research Assistant (12 months L5) to be appointed for WP1 at City University 1.0FT Research Fellow in Modelling (18 months L7) to be appointed for WP2 at City University Crabb (20% FT) will be responsible for managing the project and writing the final report. A newly appointed part-time research assistant (RA; 0-12 months) will carry out the survey work for WP1 directed by Crabb and Lemer (consultant, approx 5% FT). Lemer will also oversee the clinical audit, conduct the survey of NHS service managers and oversee interviews with Heads of Glaucoma services at NHS Hospital Trusts. A newly appointed full time research fellow (RF) with experience in both statistics and health economics will carry out the modelling and data analysis for WP2 (0-18 months) and will be directed by Crabb and Garway-Heath (5% FT). Hernandez (20% FT) will be responsible for the economic analyses and will also direct the RF. Bronze will be involved in the study design as a patient representative and will also use her extensive experience in publishing and editing to oversee the final written report. Woodfield will act as supervisor and mentor on all aspects of the qualitative research (WP1.3 and 1.4). Results will be communicated effectively to a wide variety of academic, policy and service audiences. In particular Crabb and Garway-Heath will organise a special interest group meeting as part of the annual United Kingdom and Eire Glaucoma Society meeting in December 2012 to disseminate findings from the project. Collaborators The following collaborators will form a project advisory group that will convene at City University London at 6 months and 12 months into the project. Jennifer Burr (chair) is Director of the Centre for Healthcare Randomised Trials and Senior Clinical Research Fellow in Health Services Research at the University of Aberdeen. Burr is an expert in health care evaluation in relation to eye disease, and more widely around the design, conduct and analysis of randomised controlled trials of complex interventions, diagnostic studies and decision analysis. She current leads a NIHR funded project on optimal surveillance regimes for ocular hypertension (a risk factor for glaucoma) (HTA 07/46/02) and on a MRC funded trial platform grant developing the [10/2000/68] [Crabb] protocol version: [1] [ ]

13 intervention and outcome components of a proposed randomised controlled trial of screening for glaucoma. Edward White, Chief Technician in the Moorfields Eye Hospital Glaucoma Research Unit, has worked with a variety of clinical and research patients, with visual field testing being a major element of that work, performing more than 10,000 visual field tests in the course of 12 years at the unit. David Wright is the Chief Executive of the International Glaucoma Association (IGA). The IGA is the charity for people with glaucoma, with the mission to raise awareness of glaucoma, promote research related to the disease and to provide support to patients and all those who care for them. Heather Waterman, Professor of Nursing and Ophthalmology at the University of Manchester, leads an ophthalmology nursing research team with special interest in glaucoma. She also has a long standing interest in participatory research methodologies and holds a collection of NIHR grants. Ananth Viswanathan is a consultant ophthalmologist and Senior Lecturer at the Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and the UCL Institute of Ophthalmology, London. Viswanathan is an expert in visual field analysis and is the author of software used for the management of visual field follow up. Rizwan Malik is a Clinical Lecturer in Ophthalmic Translational Research at the Biomedical Research Centre for Ophthalmology. Malik s research interests include glaucoma, perimetry and imaging. Planned or active related research grants (including NIHR) Crabb is currently a principal-investigator or co-investigator on a series of project grants from the US National Institute for Health (NIH), International Glaucoma Association, Medical Research Council (MRC) and UK Guide Dogs for the Blind Association. Crabb and Garway-Heath are CIs on an MRC strategic grant award; G85359, November January Developing the intervention and outcome components of a proposed randomised controlled trial of a national screening programme for open angle glaucoma (OAG). Crabb and Garway-Heath are CIs NIHR funded project on optimal surveillance regimes for ocular hypertension (a risk factor for glaucoma) (HTA 07/46/02). Crabb previously held an NHS New and Emerging Applications of Technology (NEAT) Awards (previous to NIHR i4i programme) for a project entitled Detecting Glaucoma: PC based perimetry. Garway-Heath has recently been awarded the prestigious status of NIHR Senior Investigator (only six such positions in Ophthalmology in the UK). 10. References: Burr, J.M., Mowatt, G., Hernández, R., Siddiqui, M.A.R., Cook, J., Lourenco, T. et al. (2007). The clinical and cost-effectiveness of screening for open angle glaucoma: a systematic review and economic evaluation. Health Technology Assessment Vol.11: No. 41. [10/2000/68] [Crabb] protocol version: [1] [ ]

14 Burr J, Kilonzo M, Vale L, and Ryan M. Developing a Preference Based Glaucoma Utility Index using a Discrete Choice Experiment. Optometry and Vision Science. 2007; 84: Briggs, A.S, Schulper, M., and Cllaxton, K. (2006). Decision modelling for health economic evaluation. Oxford: Oxford University Press. Chauhan, B.C., Garway-Heath, D.F., Goñi, F.J., Rossetti, L., Bengtsson, B., Viswanathan, A.C., Heijl, A. (2008) Practical recommendations for measuring rates of visual field change in glaucoma. Br J Ophthalmol 2008;92: Crabb, D.P., and Garway-Heath, D.F, (2009). Wait and See: Varying the Interval Between Visits to Get Better Estimates of the Rate of Visual Field Progression in Glaucoma. Invest Ophthalmol Vis Sci 50: E-Abstract Gardiner, S.K. and Crabb, D.P. (2002). Frequency of testing for detecting visual field progression. Br J Ophthalmol 86: Gardiner, S.K. and Crabb, D.P. (2002). Examination of different pointwise linear regression methods for determining visual field progression. Invest Ophthalmol Vis Sci 43: Hernández, R., Burr, J.M., Vale, L. for the OAG screening project group. (2008) Economic evaluation of screening for open angle glaucoma. International Journal of Technology Assessment in Health Care. 24:2. Karnon J. (2003) Alternative decision modelling techniques for the evaluation of health care technologies: Markov processes versus discrete event simulation. Health Econ 12: Owen, V.M.F., Crabb, D.P., White E.T., Viswanathan, A.C., Garway-Heath, D.F, and. Hitchings, R.A. (2008). Glaucoma and fitness to drive: using binocular visual fields to predict a milestone to blindness. Invest Ophthalmol Vis Sci 49: Sharma, A, Jofre-Bonet, M, Panca M, Lawrenson, J.G., and Murdoch, I. (2010). Hospital-based glaucoma clinics: what are the costs to patients? Eye 24, vangestel, A., Severens, J.L., Webers, C.A., Beckers, H.J., Jansonius, N.M., and Schouten, J.S. (2010). Modeling complex treatment strategies: construction and validation of a discrete event simulation model for glaucoma. Value Health 13: Wall, M., Johnson, C.A., Kardon, R.H., and Crabb, D.P. (2009). Use of a Continuous Probability Scale to Display Visual Field Damage. Arch Ophthalmol. 127: [10/2000/68] [Crabb] protocol version: [1] [ ]

15 1 (from page 9) We will use UK general population representative tariffs to calculate QALYs [Kind et al 1999]. This is the usual approach as the decision on provision of service is done according to preferences for the UK as a whole. The criticism is that these might be far from the patient s preferences, there might be lack of information about the condition, or the instrument might not be sensitive to quality of life changes for the particular condition. We have access to individual patient data on the Glaucoma Utility Index [Burr et al 2007] from a project where they also collected EQ5D on glaucoma population and we can use these for sensitivity analysis. Kind P, Hardman G, Macran S. UK population norms for EQ-5D. Discussion Paper 172. York: The Centre for Health Economics, University of York; This protocol refers to independent research commissioned by the National Institute for Health Research (NIHR). Any views and opinions expressed therein are those of the authors and do not necessarily reflect those of the NHS, the NIHR, the HSR programme or the Department of Health. [10/2000/68] [Crabb] protocol version: [1] [ ]