Details of HTA project
Last updated: 9 May 2012 - Next update due: 16 May 2012
Research type: |
Primary Research (e.g. trial) |
Project title: |
A longitudinal cohort study of people with lysosomal storage disorders |
Project ref: |
05/04/01 |
Cost: |
£1,489,077 |
Chief Investigator : |
Professor Stuart Logan, Professor of Paediatric Epidemiology, Institute of Health Services Research, Peninsula Medical School |
Project Website |
http://sites.pcmd.ac.uk/ncslsd/ |
Start Date: |
May 2007 |
Estimated date of publication in HTA journal series: |
February 2013. This project is at the editorial review stage. Delays in the review process can cause the forecast publication date to be delayed. |
Plain English Summary |
Lysosomal storage disorders are a group of rare, inherited diseases. In total they affect fewer than 1:7000 people. Traditionally, the therapeutic options for lysosomal storage disorders have focussed on managing the symptoms of the disease rather than treating the disease itself. However, in recent years, treatments which address the cause of the disease, the enzyme deficiency, are being developed for these disorders. Enzyme replacement therapies are now available for the treatment of Gauchers, Fabrys and MPS I, and several more are being developed. People with these disorders are treated at one of six designated treatment centres in England. The Peninsula Medical School, in collaboration with the treatment centres and the support groups, will look at how effective and cost effective these therapies are. However, because these conditions are so rare, usual ways of testing how effective a treatment is, such as a randomised controlled trial, are much harder to conduct. Therefore, we hope to carry out a long term cohort study, whereby we collect data, at each centre, from all consenting adults and children with these conditions. By following people with these conditions over a period of time we will better understand how effective treatments are, when the best time to start giving these treatments is, what the appropriate dosing schedules are, and which symptoms led to the diagnosis of the disorder. Another aspect of the study will be to estimate the value for money of these treatments. In order to do this we will look at how frequently people use the NHS, the cost of their treatment, related costs to their family, and compare these for people who are receiving treatment with those people who are not, or for whom no treatment is currently available. This study is intended to last three years in the first instance and, in addition to addressing specific questions, will create a valuable research resource for patients and clinicians. |
Project Abstract: |
Design: A longitudinal, prospective cohort study involving all adults and children with lysosomal storage disorders treated within the designated English treatment centres. Individual prospective and retrospective patient data will be collected from all consenting adults and children. Setting and Target Population: The study will initially collect data on conditions for which ERT is currently available or being developed, although it is intended that eventually all children and adults diagnosed with an LSD will form part of the study. We believe that the majority of people with lysosomal storage disorders will be referred to these centres, regardless of whether there is a specific treatment available; where there is no specific treatment, people receive palliative care from these centres. It is intended to seek consent for participation when people attend the treatment centres; if informed consent is given, individual patient data, retrospective and prospective, will be entered on to a dedicated database at each centre. Health Technologies being assessed: To conduct a prospective cohort study of people in England with a lysosomal storage disorder to determine natural history and estimate effectiveness and cost-effectiveness of current and potential treatment strategies. Measurement of cost and outcomes: The database will contain longitudinal individual-level patient data for all consenting patients attending the participating treatment centres. Natural History: Data will be analysed to describe the natural history of treated and untreated LSDs. Key outcome measures relevant to each disorder will be analysed by genotype where this information is available and where there are sufficient numbers of patients with a specific genotype. Effectiveness of treatment: For each condition, different approaches will be needed to estimate the effectiveness of ERT. The approach will depend largely on the amount of data available on untreated patients. Where data are not available for significant numbers of untreated patients, treatment efficacy will be estimated by taking advantage of the fact that the age and stage of their condition at which patients have begun taking ERT was dependent on the time when the treatment first became available. Historical data are available for many of these patients on their clinical condition at the time of beginning treatment while for others we will have data only on current clinical situation. The analysis of the available data will require (a) time series analyses of changes in outcome measures and resource use before and after treatment, taking account of a range of covariates (e.g. baseline severity, demographic characteristics) and (b) extrapolation of pre- and post-treatment data to estimate the likely lifetime costs and effects in untreated and treated cohorts of patients. Uncertainty will be addressed in all analyses by a range of sensitivity analyses, including, where appropriate, stochastic and probabilistic methods. Comparison of the effectiveness of agalsidase alpha and agalsidase beta in Fabry disease: Both agalsidase alpha and agalsidase beta are licensed for use in the UK for the treatment of Fabry disease. There is a five fold difference in the licensed dosing regimen although costs per patient are broadly similar. It appears that, although all centres use both drugs, there has been tendency for each centre to use one or other as their initial drug of choice. This it appears has been determined mainly by historical reasons based partly upon which drugs trials they were involved in. There are national guidelines for the initiation of therapy to which all Centres adhere which suggests that the populations receiving either treatment are likely to be broadly similar. We will compare the outcome of treatment depending on which of the two drugs patients were initially assigned (the equivalent of an intention to treat analysis) in a multi-variate model allowing for potential confounding variables. We will in addition compare recorded side-effects and frequency of switching treatments. |
NRR* number, if applicable: |
N0484190626 (*National Research Register). The National Research Register was a public database of ongoing and recently completed research projects funded by, or of interest to, the United Kingdom's National Health Service (NHS). It is now an archive of projects from early 2000 to September 2007. Search the NRR archive. |
Project Protocol: |
Project protocol (pdf format, 257 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1538 |
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