Introduction

In 2003, the National Institute for Clinical Excellence (NICE; now the National Institute for Health and Clinical Excellence) issued guidance to the NHS for a new, expensive treatment for ‘wet’ or neovascular age-related macular degeneration (nAMD) called verteporfin photodynamic therapy (VPDT). The guidance recommended treatment for the subtypes of nAMD for which the benefit from VPDT had been observed to be largest in phase 3 licensing trials [the ‘TAP’ (Treatment of Age-related macular degeneration with Photodynamic therapy) trials] but mandated the collection of robust information on vision, quality of life and the costs of having and treating nAMD for subtypes for which the cost-effectiveness of VPDT was less certain. The VPDT cohort study was set up to provide evidence to inform a future review of VPDT by NICE, to monitor compliance with the NICE guidance and to allow treatment of some subtypes of nAMD in compliance with the ‘only-in-research’ recommendation of the NICE guidance.

Objectives

The VPDT cohort study aimed to answer the following questions:

1. Is VPDT in the NHS provided as in randomised trials?
2. Is ‘outcome’ the same in the NHS as in randomised trials?
3. Is ‘outcome’ the same for patients who would have been ineligible for randomised trials?
4. Is VPDT safe when provided in the NHS?
5. How effective and cost-effective is VPDT?

Methods and participants

Results

Data were submitted by 47 participating hospitals for a total of 8323 treated eyes in 7748 patients. Key missing data (e.g. baseline BCVA, no follow-up data) reduced these numbers to 6647 eyes in 6223 patients. Only eyes which were treated > 350 days (1 year) before the most recent data submission, or which had completed treatment, were analysed; 4919 eyes in 4566 patients met this criterion. The number of eyes classified against eligibility for the TAP trial were 1227 EFT, 1187 IFT and 1629 UNC. Responses to at least one HRQoL and resource use questionnaire were submitted for about 2000 patients (the number varied by questionnaire).

Comment and conclusions

The main findings were that (i) VPDT was administered much less frequently in routine clinical practice than in the TAP trial; (ii) in routine clinical practice, patients were followed much less frequently than in the research setting of the TAP trial, with attendance tending to stop once BCVA had dropped; (iii) for the EFT group, deterioration in BCVA over time was similar to that in the TAP trial; (iv) there was no evidence that safety was worse than in the TAP trial; and (v) the estimated cost per QALY was similar to the highest previous estimate.

The main limitation was the exclusion and early loss to follow-up of some patients, who are likely to have been those with a worse than average outcome; this limitation would have led treatment frequency to be overestimated and deterioration in BCVA and cost per QALY to be underestimated.

A number of observations on the introduction of this technology into routine clinical practice can be made: (i) there was wide variation in the readiness of centres to follow a proscribed protocol including follow-up; (ii) there was variable engagement by centres with the collection of data, with improvement in data quality occurring over time only at centres with highly committed research-focused staff; (iii) provider organisations had varying degrees of difficulty in establishing and maintaining consistent provision to the service specification required by the national commissioning and professional bodies.

Implications for practice

Implications for practice do not relate to the use of VPDT to treat nAMD because VPDT has now been superseded by the introduction of new treatments.

• The small number of treatments administered suggests that treatment regimens receiving marketing authorisation may overestimate the intensity of treatment required. This is potentially an important consideration in relation to other new health technologies.
• This limitation of loss to follow-up should be carefully considered in the design of similar studies for interventions requiring treatment or follow-up over many months, especially if the effectiveness of an intervention is not dramatic.
• Use of VPDT should be limited to (a) circumstances in which newer technologies are contraindicated or refused by patients or (b) categories of age-related macular degeneration such as polypoidal choroidopathy or other diseases with neovascularisation arising from the choroid.
• Appraisal of a technology that benefits one eye should evaluate the benefit at the level of a person, not an eye.
• The consequences of the shallow gradients of relationships (a) between BCVA and European Quality of Life-5 Dimensions utility and (b) between BCVA and health and social services resource use/cost need to be considered carefully when appraising other technologies to treat eye diseases that impair vision.

Research recommendations

Similarly, our research recommendations are outside the context of nAMD:

• Further studies are required to investigate the effectiveness and cost-effectiveness of VPDT for neovascularisation due to myopia, inflammation and other choroidal diseases including central serous chorioretinopathy.
• Modification of the effectiveness of new interventions for nAMD by covariates found to influence effectiveness in this study should be studied.
• The relationships between BCVA and HRQoL/health and social services resource use are important for modelling cost-effectiveness. Further research should investigate how widely these relationships can be applied, for example to other diseases that reduce BCVA.

Conclusions

The VPDT cohort study model was successful in establishing a network of research expertise, expanding research capacity, engaging professional bodies and developing purchaser–provider relationships around research and development. It formed a structure for the managed introduction of the technology including the necessary training and service specification development. The success of the model was limited by the freedom of providers to divert investment into other services and to revise care pathways. Improvements in models of the introduction of costly new technology into the NHS are recommended.

Publication

• Reeves BC, Harding SP, Langham J, Grieve R, Tomlin K, Walker J, et al. Verteporfin photodynamic therapy for neovascular age-related macular degeneration: cohort study for the UK. Health Technol Assess 2012;16(6). [PubMed: 22348600]

NIHR Health Technology Assessment programme

The Health Technology Assessment (HTA) programme, part of the National Institute for Health Research (NIHR), was set up in 1993. It produces high-quality research information on the effectiveness, costs and broader impact of health technologies for those who use, manage and provide care in the NHS. ‘Health technologies’ are broadly defined as all interventions used to promote health, prevent and treat disease, and improve rehabilitation and long-term care.

The research findings from the HTA programme directly influence decision-making bodies such as the National Institute for Health and Clinical Excellence (NICE) and the National Screening Committee (NSC). HTA findings also help to improve the quality of clinical practice in the NHS indirectly in that they form a key component of the ‘National Knowledge Service’.

The HTA programme is needs led in that it fills gaps in the evidence needed by the NHS. There are three routes to the start of projects.

First is the commissioned route. Suggestions for research are actively sought from people working in the NHS, from the public and consumer groups and from professional bodies such as royal colleges and NHS trusts. These suggestions are carefully prioritised by panels of independent experts (including NHS service users). The HTA programme then commissions the research by competitive tender.

Second, the HTA programme provides grants for clinical trials for researchers who identify research questions. These are assessed for importance to patients and the NHS, and scientific rigour.

Third, through its Technology Assessment Report (TAR) call-off contract, the HTA programme commissions bespoke reports, principally for NICE, but also for other policy-makers. TARs bring together evidence on the value of specific technologies.

Some HTA research projects, including TARs, may take only months, others need several years. They can cost from as little as £40,000 to over £1 million, and may involve synthesising existing evidence, undertaking a trial, or other research collecting new data to answer a research problem.

The final reports from HTA projects are peer reviewed by a number of independent expert referees before publication in the widely read journal series Health Technology Assessment.

Criteria for inclusion in the HTA journal series

Reports are published in the HTA journal series if (1) they have resulted from work for the HTA programme, and (2) they are of a sufficiently high scientific quality as assessed by the referees and editors.

Reviews in Health Technology Assessment are termed ‘systematic’ when the account of the search, appraisal and synthesis methods (to minimise biases and random errors) would, in theory, permit the replication of the review by others.

The research reported in this issue of the journal was commissioned by the HTA programme as project number 03/36/01. The contractual start date was in December 2003. The draft report began editorial review in December 2010 and was accepted for publication in June 2011. As the funder, by devising a commissioning brief, the HTA programme specified the research question and study design. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the referees for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report.

The views expressed in this publication are those of the authors and not necessarily those of the HTA programme or the Department of Health.

Editor-in-Chief: Professor Tom Walley CBE

Series Editors: Dr Martin Ashton-Key, Professor Aileen Clarke, Dr Tom Marshall, Professor John Powell, Dr Rob Riemsma and Professor Ken Stein

Associate Editor: Dr Peter Davidson