A national database is tracking every person in England diagnosed with a lysosomal storage disorder—a group of rare, often devastating genetic diseases—to measure how well current treatments actually work and what they cost over a patient’s lifetime. These disorders, which include Fabry disease, Gaucher disease, and dozens of others, are individually rare but collectively affect hundreds of patients. Many are treated with enzyme replacement therapy (ERT), but the evidence for its long-term effectiveness and cost-effectiveness is patchy. The study fills that gap by collecting both retrospective and prospective data from all consenting patients at England’s designated treatment centres, covering treated and untreated individuals. For Fabry disease specifically, the researchers will compare the two licensed drugs—agalsidase alpha and agalsidase beta—which have a fivefold difference in dosing but similar costs, exploiting the fact that centres historically favoured one drug over the other. If successful, this work will give the NHS and NICE robust, real-world data on which treatments extend life and improve quality of life, and at what cost. That could directly influence commissioning decisions, ensuring that limited NHS budgets are spent on therapies that deliver genuine benefit for patients with these lifelong conditions.
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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 confou
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