Duchenne Muscular Dystrophy (DMD) is a rare disease that mainly affects males. It is a muscle weakening disease and patients will eventually suffer breathing and heart problems, leading to an early death by their twenties. Steroids are the main treatment for patients with DMD to help preserve muscle, breathing and heart function and to prolong life.
As possible new treatments are tested in clinical trials, decision-makers such as the National Institute for Health and Care Excellence (NICE) must decide which are cost-effective and so whether to reimburse the drug, for example by making it accessible via the NHS.
One tool the decision-makers need is a model that describes the disease pathway for patients who haven’t taken any experimental treatment. This model will work out how quickly patients move from one stage of the disease to the next. New treatments should slow down this progression. An important part of this model is the rate and stage at which patients die. Currently, there is little information on this for UK patients.
The objective of this research is to investigate the rates at which patients with DMD die in the UK for specific ages and to see whether this depends on steroid use. This data will better reflect the current standards of care compared to previously reported studies. The research will also develop methods for building this model to account for the fact that, like many rare diseases, the evidence pool on DMD patients is limited and comes from a variety of sources.
Duchenne Muscular Dystrophy (DMD) is a rare, muscle-degeneration disease predominantly affecting males. The mainstay of treatment for DMD are corticosteroids, which have been shown to delay the decline in many functions and even prolong life. Many new treatments for DMD are currently in development. A multi-state natural history model is being constructed that captures the full disease pathway of DMD and to which treatment effects of new medicines can be applied to work out cost-effectiveness, for health technology decision-makers such as NICE.
External data has been used to populate the majority of the natural history model; however, mortality data is severely lacking, especially for UK patients treated with more recent standards of care. Additionally, the order in which patients progress through later stages of the disease is a key part of the model for which evidence is lacking.
The primary objective of this research is to estimate age-specific mortality rates for males diagnosed with DMD. The impact of corticosteroids on these mortality rates will be investigated. These rates will be used to inform a natural history model of DMD patients. New methods for constructing multi-state natural history models of rare diseases will also be developed in this research to reflect the often varied nature of data sources.
The exposure is patients with a DMD diagnosis and the outcome is all-cause death, with secondary disease characteristics of spinal surgery and cardiomyopathy also of interest. Death will be defined by ONS mortality data, where available; otherwise, by CPRD primary data. Where death date is missing, the date the patient was last known to be alive will be informed by HES Admitted Patient Care, HES Outpatient and CPRD primary data. Mortality rates for specific ages will be estimated using survival regression. They will also be adjusted by corticosteroid use in the secondary analysis.
All-cause mortality; spinal surgery; cardiomyopathy
Mark Rutherford - Chief Investigator - University of Leicester
Jonathan Broomfield - Corresponding Applicant - University of Leicester
Keith Abrams - Collaborator - University of York
Michael Crowther - Collaborator - Karolinska Institute Sweden
Michael Sweeting - Collaborator - University of Leicester
Mark Rutherford - Collaborator - University of Leicester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation